A 20-year-old woman presented to her primary care clinic with a chief complaint of lower leg weakness and difficulty walking. The weakness she described had been worsening over the previous four days, with progressively worsening tingling and numbness of her toes bilaterally.

The day before the patient presented, she noticed numbness and paresthesia in both calves. At the time of her presentation to the clinic, she complained of low back ache, paresthesia of both hands, numbness bilaterally to her groin, difficulty sitting upright, ataxia, and a numb, thick-feeling tongue. She denied fever, neck stiffness, shortness of breath, headache, or visual changes.

The patient stated that 10 days earlier, she had developed an upper respiratory infection for which she was seen at the clinic and treated with a seven-day course of amoxicillin/clavulanate 875/125 mg twice daily. She said that she had recovered completely.

A review of the patient’s systems revealed proximal muscle weakness bilaterally (2/5) and loss of touch-pressure in the lower extremities. She was experiencing paresthesia of the hands and mild weakness bilaterally (4/5). She also walked with an ataxic gait and had reduced deep tendon reflexes in the lower limbs. All cranial nerves were intact, and her vital signs were stable.

The woman’s medical history was positive only for asthma. Her family history included ischemic stroke in the maternal grandfather and brain tumor in the paternal grandfather. Social history was positive for alcohol intake (ranging from four to 12 beers per week). The patient said she had never smoked or used illicit drugs. She was an unmarried college student, living in a dorm on campus. She participated in track at school.

The patient was admitted to the hospital telemetry step-down unit, and a neurology consultation was requested. Tests were ordered, among them MRI of the head and spine and comprehensive blood work, to rule out neurologic, infectious, or metabolic causes of the patient’s weakness; urinalysis was also obtained. These tests all yielded negative results.

A lumbar puncture performed the following day revealed a cerebrospinal fluid (CSF) protein level of 570 mg/L (normal range, 150 to 450 mg/L). Leukocytes numbered 2 cells/mm³ (normal count, 0 to 10 cells/mm³).

Based on the patient’s presentation, history, and symptoms, a neurologist made a diagnosis of Guillain-Barré syndrome. It was decided that no electromyographic (EMG) study was required to rule out other disease processes (eg, spinal cord disease, multiple sclerosis, tumors).

The patient underwent a five-dose course of immunomodulatory therapy with IV immunoglobulin (IVIG). In the step-down unit, she experienced one incident of sinus bradycardia (ie, resting heart rate between 40 and 50 beats/min). Her blood pressure remained stable, as did her respiratory status, according to peak expiratory flow measured frequently at her bedside.

Physical therapy was initiated, consisting of passive and active range of motion, crossovers with the patient’s feet, and stair training. This was done in response to a complaint of ankle weakness, and it helped to strengthen weakened muscles and improve alignment while the patient was bedridden and in a weakened, fatigued state. Additionally, the patient was given enoxaparin, wore antiembolic hose, and used sequential compression devices while in bed. As a result of these measures, she never experienced a pulmonary embolus or deep vein thrombosis (DVT) as a result of being immobilized.

By the seventh day of hospitalization, the patient had stable vital signs and improved lower limb strength, and numbness was resolving in her hands and lower extremities. She was discharged to home, with physical therapy to resume on an outpatient basis.

Discussion
Guillain-Barré syndrome (GBS), an acute immune-mediated paralytic disorder,¹ manifests in the form of weakness and diminished reflexes. Affecting the peripheral nerves, GBS is characterized by progressive symmetrical ascending weakness with varying degrees of sensory complaints.^2,3

GBS occurs worldwide, and incidence is estimated between 1.1 and 1.8 cases per 100,000 persons.⁴ In the United States, GBS can be found in all age-groups, with peak incidence noted in elderly persons and young adults.^5,6 Even with treatment, 3% to 10% of patients are reported to die of this illness, and 20% cannot walk six months after symptom onset.⁷ In one prospective population-based study of patients with confirmed GBS, 6% of patients died within 30 days of symptom onset, often as a result of respiratory complications.⁸

GBS is a postinfectious disorder, with cases developing several days or weeks after a viral or bacterial illness—most commonly, an upper respiratory infection or diarrhea (see Table 1^9-13). The most common trigger of GBS is infection with the bacterial microorganism Campylobacter jejuni (occurring in 15% to 40% of patients with GBS),^9,14 a pathogen that can produce demyelination-causing antibodies. Other responsible pathogens include cytomegalovirus and Epstein-Barr virus.⁹ In a process called molecular mimicry, the immune system is unable to distinguish the amino acid of an infectious organism from the proteinaceous content of the peripheral nerve.¹⁵ Subsequently, the immune system attacks and destroys the myelin sheath.

An example of this is the apparent cross-reaction of the ganglioside GM1 with C jejuni lipopolysaccharide antigens.^14,15 The resulting effect is immunologic damage to the peripheral nervous system. The flaccid paralysis that occurs in patients with GBS is thought to be caused by lymphocytic infiltration and complement activation of the spinal roots and peripheral nerves, where macrophages strip the myelin.^5,15,16

Stages and Variants
Three stages characterize the course of GBS. The acute phase, which lasts one to four weeks, begins with onset of symptoms and persists until the associated neurologic deterioration has ceased. During the second phase, the plateau period, symptoms persist with no further deterioration; this stage can last several days to several weeks or months. The final phase, the recovery period, can last from four months to two years after symptom onset.^15,17,18

The clinical course of GBS is highly variable and in many cases difficult to predict. Certain factors have been associated with a poor outcome: advancing age, previous presence of diarrhea, need for mechanical ventilation, an extended plateau phase, and a lower patient score on the Erasmus GBS Outcome Scale,¹⁹ when measured two weeks after GBS onset.^8,20 This score can help predict the patient’s chance of independent walking after six months.^15,19

Although the classic presenting symptom of GBS is symmetric ascending weakness, several disease variants have been identified, with differing symptoms and degrees of recovery. These variants also differ in terms of the muscle groups affected; in some, visual defects may be present at onset. GBS variants include²¹:

• Acute motor axonal neuropathy (AMAN)^1,22

• Acute inflammatory demyelinating polyneuropathy (AIDP)¹

• Pharyngeal-cervical-brachial variant²³

• Purely sensory variant24

• Miller-Fisher syndrome, which manifests with ophthalmoplegia, in addition to ataxia and areflexia²⁵

• Axonal form.^5,21

AMAN and AIDP are the most common subtypes of GBS.¹

Symptoms, Signs, and Disease Manifestations
Limb weakness, the classic presenting symptom of GBS, is both symmetrical and ascending. Weakness can develop acutely and progress over days to weeks.^2,15 Hughes and Cornblath²⁶ also note pain, numbness, and paresthesias among the initial symptoms of GBS. Others include sensory changes, cranial nerve involvement, various autonomic changes, and respiratory or oropharyngeal weakness. Reflexes, particularly the tendon reflexes, may be diminished or absent.^15,18,21 In many cases, sensory changes (ie, pain) may precede the onset of weakness, often making diagnosis difficult.¹⁵

Cranial nerves most commonly affected are V, VI, VII, X, XI, and  XII, with manifestations that include dysphagia, dysarthria, diplopia, limitation to eye movements, and facial droop and weakness. Usually facial and oropharyngeal weakness occur after the extremities and trunk are affected. Blindness may occur if demyelination of the optic nerve occurs; this is seen in Miller-Fisher syndrome.^10,15,25,27

In GBS, many patients report pain, which can present as bilateral sciatica or as throbbing or aching in the large muscles of the upper legs, flanks, or back.28 This pain, which results from the demyelination of the sensory nerve fibers, can be severe.10

Patients with GBS may experience manifestations of autonomic nervous system dysfunction—for example, arrhythmias, hypotension or hypertension, urinary retention, cardiomyopathy, and paralytic ileus.^10,20 Dysautonomia often impedes patients’ progress in inpatient rehabilitation. Patients may have persistent problems involving postural hypotension, hypertension, excessive sympathetic outflow, or bladder and bowel dysfunction.²⁹

Blood pressure fluctuations, often attributed to changes in catecholamine levels and disturbances in the baroreceptor reflex pathway, are common and are considered characteristic of GBS. Transient or persistent hypotension is caused by the dysregulation of the parasympathetic and sympathetic systems, with subsequent alterations in venomotor tone.³ Additionally, an increased sensitivity to catecholamine can lead to cardiovascular disturbances, resulting in denervation hypersensitivity and impairment of the carotid sinus reflex.

Arrhythmias occur in perhaps half of patients with GBS. The most common is sustained sinus tachycardia, which usually requires no treatment. Bradycardia leading to atrioventricular blocks and asystole is believed to result from afferent baroreceptor reflex failure. Treatment may be required—either administration of atropine or insertion of a pacemaker, depending on the severity of the arrhythmia.^3,10

Myocardial involvement can range from asymptomatic mycocarditis to neurogenic stunned myocardium and heart failure. Patients with ECG abnormalities should undergo two-dimensional echocardiographic studies and other testing to explore cardiac involvement. Acute coronary syndromes, including ST-segment elevation MI, have been reported, in some cases associated with IVIG treatment. In one patient, coronary spasm was reported, with clean coronary arteries found on cardiac catheterization.³

Patients with GBS are at risk for compromised neuromuscular respiratory function; demyelination of the nerves that innervate the intercostal muscles and the diaphragm can result in respiratory failure. Key clinical indicators of respiratory muscle fatigue include tachypnea, diaphoresis, and asynchronous movements of the abdomen and chest;¹⁰ other symptoms relevant to respiratory or oropharyngeal weakness include slurred speech, dyspnea (with or without exertion), difficulty swallowing, and inability to cough.^2,10 Serial respiratory function testing is advisable to detect patients at risk for respiratory failure.³⁰

Diagnosis
Guillain-Barré is a syndrome diagnosed by a collection of symptoms (see Table 2^2,21,31), including subacute developing paralysis, symmetrical bilateral weakness beginning at onset, and diminishing to absent reflexes.^21,31 Other causes for rapidly developing weaknesses should be ruled out (see Table 3^10,21,26,31). Lumbar puncture typically shows increased protein levels with a normal white cell count; however, neither this test nor electrophysiologic evaluation offers significant value for diagnosis of GBS.^21,26,31

During the acute phase of GBS (within three weeks of onset), there is found an elevation of CSF protein (> 550 mg/L) without an elevation in white blood cells. This phenomenon, called albuminocytologic dissociation, reflects inflammation of the nerve roots and is considered the hallmark of GBS.²

MRI can also facilitate the diagnosis of GBS; it demonstrates anterior and posterior intrathecal spinal nerve roots and cauda equina.³² In patients with GBS, evidence supporting breakdown of the blood–nerve barrier can be seen in abnormal gadolinium enhancement of the intrathecal nerve roots on MRI.³³

When electrophysiologic studies are performed, they typically reveal slowing nerve conduction, prolonged distal latencies, and partial motor conduction block.³⁴ The characteristic finding of early demyelination is conduction block, a reduction in the amplitude of the muscle action potential after stimulation of the distal, as opposed to the proximal, nerve.²⁸ Nerve conduction studies may help in the diagnosis and classification of GBS—and, to a limited extent, formulation of a prognosis. Such alternative diagnoses as myositis and myasthenia gravis may be excluded by neurophysiology.²⁶ Early in GBS, neurophysiologic abnormalities may be very mild or occasionally normal; test results may not correlate with clinical disability.^35,36

The clinician cannot depend on clinical features alone to predict respiratory decline.³¹ Frequent evaluations of respiratory effort, by measurement of maximal inspiratory pressures and vital capacity, should be performed at the bedside to monitor diaphragmatic strength. Respiratory ventilation should be initiated if the patient becomes hypoxic or experiences a rapid decline in vital capacity (ie, below 60% of predicted value).¹⁰ Mechanical ventilation is more likely to be required in patients with a negative inspiratory force of less than 30 cm H2O.³¹

Treatment
Guillain-Barré syndrome has an acute onset and progression. Patients quickly become nonambulatory and may require total ventilation due to paralysis. Therapeutic options are IVIG or plasmapheresis (plasma exchange).^37-40 Corticosteroids do not appear to benefit patients with GBS.^41,42

Several mechanisms appear to contribute to the effectiveness of immunoglobulin.^38,39 Infused IVIG interferes with antigen presentation, inhibits antibody production, neutralizes pathologic autoantibodies, and modulates other immunologic events involved in the pathogenesis of autoimmune neuromuscular diseases, including GBS.⁴³ Adverse reactions, which are usually minor, include headache, fever, chills, myalgia, and malaise. In rare instances, anaphylaxis or renal failure may occur.^15,44

In plasmapheresis, blood is removed from the body and dialyzed, with circulating antibodies and immunoglobulins removed from the plasma; fresh frozen plasma, albumin, or saline is administered. This treatment, performed via central venous catheter, should be initiated as soon as possible after onset of symptoms but can be implemented as late as 30 days after GBS onset. Plasmapheresis requires personnel trained in dialysis, which may not be performed in all hospitals. Possible adverse events include infection and hemorrhage. Laboratory values must be monitored for hypokalemia and hypocalcemia.^45,46

Supportive Care
Patients with GBS require intensive care and very close monitoring for complications of respiratory difficulty and autonomic dysfunction. Individualized programs should be initiated for patients in the acute phase of GBS, aimed at the prevention of contractures and skin breakdown.¹⁰ Exercise programs, as conducted with the case patient, should also help relieve the fatigue syndromes that accompany GBS.

Immobilization associated with bed rest incurs a risk for pulmonary emboli and DVT; this has been found true during the first 12 weeks after symptom onset in patients with GBS who remain immobile.⁴⁷ The use of antiembolic hose and sequential compression devices can help reduce the risk for thrombotic events.¹⁰ Use of enoxaparin or heparin is recommended for nonambulating patients until they are able to walk, with Gaber et al⁴⁷ specifying the use of low-molecular-weight heparin to reduce, but not eliminate, the risk for DVT.

The pain associated with GBS can be severe. Narcotic analgesics may be administered with careful monitoring of autonomic denervation. Long-term management of neuropathic pain may require adjuvant therapy, such as tricyclic antidepressants, gabapentin, or tramadol hydrochloride.¹⁰ According to Pandey et al,⁴⁸ gabapentin alone may suffice for pain control in GBS, with minimal adverse effects. In certain rehabilitation facilities, tricyclic antidepressants, capsaicin, and transcutaneous nerve stimulation have been reported effective; during the early stages of treatment, until these treatments reach their full effect, pain medications such as tramadol or narcotics can provide temporary relief.²⁹

More than one-half of patients with GBS in the acute phase can develop ileus. Constipation can also occur as a result of pain medication use, prolonged bed rest, and poor intake. Auscultation of bowel sounds and abdominal assessment should be performed daily to monitor for ileus. Hughes et al¹⁰ do not recommend the use of promotility drugs in patients with dysautonomia.

After hospital discharge, easy fatigability can affect work and social activities. With continued physical therapy, occupational therapy, and monitoring, however, patients with GBS can expect to return to an optimal level of functioning. Speed of recovery varies with these patients from a few months to several years, depending on such factors as age and the extent to which axonal degeneration has occurred.^6,49

The Case Patient
For several weeks after discharge, the case patient continued to experience fatigue, low back pain, and general muscle pain. With her family’s support, she continued to receive outpatient physical therapy, and within one month she had regained her ankle strength. She was soon able to resume her classes, despite some lingering fatigue.

Conclusion
Guillain-Barré syndrome is a potentially life-threatening disease whose symptoms health care providers need to recognize quickly to provide prompt treatment. Supportive care for both patient and family is of key importance for maximum rehabilitation and return to the previous lifestyle. The clinical course of GBS is highly variable and difficult to predict. The patient’s outcome depends on several factors, including age and severity of illness. GBS patients can experience long-term psychosocial effects.

References
1. Magira EE, Papaioakim M, Nachamkin I, et al. Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP. J Immunol. 2003;170(6):3074-3080.

2. Tremblay ME, Closon A, D’Anjou G, Bussières JF. Guillain-Barré syndrome following H1N1 immunization in a pediatric patient. Ann Pharmacother. 2010;44(7-8):1330-1333.

3. Mukerji S, Aloka F, Farooq MU, et al. Cardiovascular complications of the Guillain-Barré syndrome. Am J Cardiol. 2009;104(10):1452-1455.

4. McGrogan A, Madle GC, Seaman HE, de Vries CS. The epidemiology of Guillain-Barré syndrome worldwide: a systematic literature review. Neuroepidemiology. 2009;32(2):150-163.

5. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009; 32(4):309-323.

6. van Doorn PA. What’s new in Guillain-Barré syndrome in 2007-2008? J Periph Nerv Syst. 2009;14(2):72-74.

7. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7(10):939-950.

8. Chiò A, Cocito D, Leone M, et al; Piemonte and alle d’Aosta Register for Guillain-Barré Syndrome. Guillain-Barré syndrome: a prospective, population-based incidence and outcome survey. Neurology. 2003; 60(7):1146-1150.

9. Hadden RD, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barré syndrome. Neurology. 2001;56(6):758-765.

10. Hughes RA, Wijdicks EF, Benson E, et al. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol. 2005;62(8):1194-1198.

11. Aluka KJ, Turner PL, Fullum TM. Guillain-Barré syndrome and postbariatric surgery polyneuropathies. JSLS. 2009;13(2):250-253.

12. Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barré syndrome. J Neurol Sci. 2003;208(1-2):39-42.

13. Lin WC, Lee PI, Lu CY, et al. Mycoplasma pneumoniae encephalitis in childhood. J Microbiol Immunol Infect. 2002;35(3):173-178.

14. Sivadon-Tardy V, Orlikowski D, Porcher R, et al. Detection of Campylobacter jejuni by culture and real-time PCR in a French cohort of patients with Guillain-Barre syndrome. J Clin Microbiol. 2010;48 (6):2278-2281.

15. van Doorn PA, Kuitwaard K, Walgaard C, et al. IVIG treatment and prognosis in Guillain-Barré syndrome. J Clin Immunol. 2010;30 suppl 1:S74-S78.

16. Kaida K, Kusunoki S. Guillan-Barré syndrome: update on immunobiology and treatment. Expert Rev Neurother. 2009;9(9):1307-1319.

17. Forsberg A, Press R, Einarsson U, et al. Disability and health-related quality of life in Guillain-Barré syndrome during the first two years after onset: a prospective study. Clin Rehabil. 2005;19(8):900-909.

18. Criteria for diagnosis of Guillain-Barré syndrome. Ann Neurol. 1978;3(6):565-566.

19. van Koningsveld R, Steyerberg EW, Hughes RA, et al. A clinical progostic scoring system for Guillain-Barré syndrome. Lancet Neurol. 2007;6(7):589-594.

20. Koeppen S, Kraywinkel K, Wessendorf TE, et al. Long-term outcome of Guillain-Barré syndrome. Neuro­crit Care. 2006;5(3)235-242.

21. Sheridan JM, Smith D. Atypical Guillain-Barré in the emergency department. West J Emerg Med. 2010;11(1):80-82.

22. Ogawara K, Kuwabara S, Koga M, et al. Anti-GM1b IgG antibody is associated with acute motor axonal neuropathy and Campylobacter jejuni infection. J Neurol Sci. 2003;210(1-2):41-45.

23. Nagashima T, Koga M, Odaka M, et al. Continuous spectrum of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. Arch Neurol. 2007;64(10):1519-1523.

24. Oh SJ, LaGanke C, Claussen GC. Sensory Guillain-Barré syndrome. Neurology. 2001;56(1):82-86.

25. Aráranyi Z, Kovács T, Sipos I, Bereczki D. Miller Fisher syndrome: brief overview and update with a focus on electrophysiological findings. Eur J Neurol. 2011 Jun 1. [Epub ahead of print]

26. Hughes RA, Cornblath, DR. Guillain-Barré syndrome. Lancet. 2005;366(9497):1653-1666.

27. Snyder LA, Rismondo V, Miller NR. The Fisher variant of Guillain-Barré syndrome (Fisher syndrome). J Neuroophthalmol. 2009;29(4):312-324.

28. Ropper AH. The Guillain-Barré syndrome. N Engl J Med.1992;326(17):1130-1136.

29. Meythaler JM. Rehabilitation of Guillain-Barré syndrome. Arch Phys Med Rehabil.1997;78(8):872-879.

30. Sharshar T, Chevret S, Bourdain F, et al; French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. Early predictors of mechanical ventilation in Guillain-Barré syndrome. Crit Care Med. 2003; 31(1):278-283.

31. McGillicuddy DC, Walker O, Shapiro NI, et al. Guillain-Barré syndrome in the emergency department. Ann Emerg Med. 2006;47(4):390-393.

32. Yikilmaz A, Doganay S, Gumus H, et al. Magnetic resonance imaging of childhood Guillain-Barré syndrome. Childs Nerv Syst. 2010;26(8):1103-1108.

33. Gonzalez-Quevedo A, Carriera RF, O’Farrill ZL, et al. An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain-Barré syndrome. Neurol India. 2009;57(3):288-294.

34. Abai S, Kim SB, Kim JP, Lim YJ. Guillan-Barré syndrome combined with acute cervical myelopathy. J Korean Neurosurg Soc. 2010;48(3):298-300.

35. Uncini A, Yuki N. Electrophysiologic and immunopathologic correlates in Guillain-Barré syndrome subtypes. Expert Rev Neurother. 2009;9(6):869-884.

36. Hadden RD, Hughes RA. Management of inflammatory neuropathies. J Neurol Neurosurg Psychiatry. 2003;74 suppl 2:ii9-ii14.

37. Raphaël JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2002;(2):CD001798.

38. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Jun 16; (6):CD002063.

39. Human immunoglobulin and the Guillain-Barré syndrome: new indication. An alternative to plasmapheresis. Prescrire Int. 2000;9(49):142-143.

40. van der Meché FG, Schmitz PI; Dutch Guillain-Barré Study Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med. 1992;327(17):1123-1129.

41. Hughes RA, Swan AV, van Doorn PA. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Feb 16;(2):CD001446.

42. Hahn AF. Guillain-Barré syndrome. Lancet. 1998; 352(9128):635-641.

43. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19):2367-2375.

44. Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokenetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol. 2009;66(5):597-603.

45. Atkinson SB, Carr RL, Maybee P, Haynes D. The challenges of managing and treating Guillain-Barré syndrome during the acute phase. Dimens Crit Care Nurs. 2006;25(6):256-263.

46. van Doorn PA. Treatment of Guillain-Barré syndrome and CIDP. J Periph Nerv Syst. 2005;10(2):113-127.

47. Gaber TA, Kirker SGB, Jenner JR. Current practice of prophylactic anticoagulation in Guillain-Barré syndrome. Clin Rehabil. 2002;16(2):190-193.

48. Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in Guillain-Barré syndrome: a double-blinded, placebo-controlled, crossover study. Anesth Analg. 2002;95(6):1719-1723.

49. de Vries JM, Hagemans ML, Bussmann JB, et al. Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease. Cell Mol Life Sci. 2010;67(5):701-713.

A 20-year-old woman presented to her primary care clinic with a chief complaint of lower leg weakness and difficulty walking. The weakness she described had been worsening over the previous four days, with progressively worsening tingling and numbness of her toes bilaterally.

The day before the patient presented, she noticed numbness and paresthesia in both calves. At the time of her presentation to the clinic, she complained of low back ache, paresthesia of both hands, numbness bilaterally to her groin, difficulty sitting upright, ataxia, and a numb, thick-feeling tongue. She denied fever, neck stiffness, shortness of breath, headache, or visual changes.

The patient stated that 10 days earlier, she had developed an upper respiratory infection for which she was seen at the clinic and treated with a seven-day course of amoxicillin/clavulanate 875/125 mg twice daily. She said that she had recovered completely.

A review of the patient’s systems revealed proximal muscle weakness bilaterally (2/5) and loss of touch-pressure in the lower extremities. She was experiencing paresthesia of the hands and mild weakness bilaterally (4/5). She also walked with an ataxic gait and had reduced deep tendon reflexes in the lower limbs. All cranial nerves were intact, and her vital signs were stable.

The woman’s medical history was positive only for asthma. Her family history included ischemic stroke in the maternal grandfather and brain tumor in the paternal grandfather. Social history was positive for alcohol intake (ranging from four to 12 beers per week). The patient said she had never smoked or used illicit drugs. She was an unmarried college student, living in a dorm on campus. She participated in track at school.

The patient was admitted to the hospital telemetry step-down unit, and a neurology consultation was requested. Tests were ordered, among them MRI of the head and spine and comprehensive blood work, to rule out neurologic, infectious, or metabolic causes of the patient’s weakness; urinalysis was also obtained. These tests all yielded negative results.

A lumbar puncture performed the following day revealed a cerebrospinal fluid (CSF) protein level of 570 mg/L (normal range, 150 to 450 mg/L). Leukocytes numbered 2 cells/mm³ (normal count, 0 to 10 cells/mm³).

Based on the patient’s presentation, history, and symptoms, a neurologist made a diagnosis of Guillain-Barré syndrome. It was decided that no electromyographic (EMG) study was required to rule out other disease processes (eg, spinal cord disease, multiple sclerosis, tumors).

The patient underwent a five-dose course of immunomodulatory therapy with IV immunoglobulin (IVIG). In the step-down unit, she experienced one incident of sinus bradycardia (ie, resting heart rate between 40 and 50 beats/min). Her blood pressure remained stable, as did her respiratory status, according to peak expiratory flow measured frequently at her bedside.

Physical therapy was initiated, consisting of passive and active range of motion, crossovers with the patient’s feet, and stair training. This was done in response to a complaint of ankle weakness, and it helped to strengthen weakened muscles and improve alignment while the patient was bedridden and in a weakened, fatigued state. Additionally, the patient was given enoxaparin, wore antiembolic hose, and used sequential compression devices while in bed. As a result of these measures, she never experienced a pulmonary embolus or deep vein thrombosis (DVT) as a result of being immobilized.

By the seventh day of hospitalization, the patient had stable vital signs and improved lower limb strength, and numbness was resolving in her hands and lower extremities. She was discharged to home, with physical therapy to resume on an outpatient basis.

Discussion
Guillain-Barré syndrome (GBS), an acute immune-mediated paralytic disorder,¹ manifests in the form of weakness and diminished reflexes. Affecting the peripheral nerves, GBS is characterized by progressive symmetrical ascending weakness with varying degrees of sensory complaints.^2,3

GBS occurs worldwide, and incidence is estimated between 1.1 and 1.8 cases per 100,000 persons.⁴ In the United States, GBS can be found in all age-groups, with peak incidence noted in elderly persons and young adults.^5,6 Even with treatment, 3% to 10% of patients are reported to die of this illness, and 20% cannot walk six months after symptom onset.⁷ In one prospective population-based study of patients with confirmed GBS, 6% of patients died within 30 days of symptom onset, often as a result of respiratory complications.⁸

GBS is a postinfectious disorder, with cases developing several days or weeks after a viral or bacterial illness—most commonly, an upper respiratory infection or diarrhea (see Table 1^9-13). The most common trigger of GBS is infection with the bacterial microorganism Campylobacter jejuni (occurring in 15% to 40% of patients with GBS),^9,14 a pathogen that can produce demyelination-causing antibodies. Other responsible pathogens include cytomegalovirus and Epstein-Barr virus.⁹ In a process called molecular mimicry, the immune system is unable to distinguish the amino acid of an infectious organism from the proteinaceous content of the peripheral nerve.¹⁵ Subsequently, the immune system attacks and destroys the myelin sheath.

An example of this is the apparent cross-reaction of the ganglioside GM1 with C jejuni lipopolysaccharide antigens.^14,15 The resulting effect is immunologic damage to the peripheral nervous system. The flaccid paralysis that occurs in patients with GBS is thought to be caused by lymphocytic infiltration and complement activation of the spinal roots and peripheral nerves, where macrophages strip the myelin.^5,15,16

Stages and Variants
Three stages characterize the course of GBS. The acute phase, which lasts one to four weeks, begins with onset of symptoms and persists until the associated neurologic deterioration has ceased. During the second phase, the plateau period, symptoms persist with no further deterioration; this stage can last several days to several weeks or months. The final phase, the recovery period, can last from four months to two years after symptom onset.^15,17,18

The clinical course of GBS is highly variable and in many cases difficult to predict. Certain factors have been associated with a poor outcome: advancing age, previous presence of diarrhea, need for mechanical ventilation, an extended plateau phase, and a lower patient score on the Erasmus GBS Outcome Scale,¹⁹ when measured two weeks after GBS onset.^8,20 This score can help predict the patient’s chance of independent walking after six months.^15,19

Although the classic presenting symptom of GBS is symmetric ascending weakness, several disease variants have been identified, with differing symptoms and degrees of recovery. These variants also differ in terms of the muscle groups affected; in some, visual defects may be present at onset. GBS variants include²¹:

• Acute motor axonal neuropathy (AMAN)^1,22

• Acute inflammatory demyelinating polyneuropathy (AIDP)¹

• Pharyngeal-cervical-brachial variant²³

• Purely sensory variant24

• Miller-Fisher syndrome, which manifests with ophthalmoplegia, in addition to ataxia and areflexia²⁵

• Axonal form.^5,21

AMAN and AIDP are the most common subtypes of GBS.¹

Symptoms, Signs, and Disease Manifestations
Limb weakness, the classic presenting symptom of GBS, is both symmetrical and ascending. Weakness can develop acutely and progress over days to weeks.^2,15 Hughes and Cornblath²⁶ also note pain, numbness, and paresthesias among the initial symptoms of GBS. Others include sensory changes, cranial nerve involvement, various autonomic changes, and respiratory or oropharyngeal weakness. Reflexes, particularly the tendon reflexes, may be diminished or absent.^15,18,21 In many cases, sensory changes (ie, pain) may precede the onset of weakness, often making diagnosis difficult.¹⁵

Cranial nerves most commonly affected are V, VI, VII, X, XI, and  XII, with manifestations that include dysphagia, dysarthria, diplopia, limitation to eye movements, and facial droop and weakness. Usually facial and oropharyngeal weakness occur after the extremities and trunk are affected. Blindness may occur if demyelination of the optic nerve occurs; this is seen in Miller-Fisher syndrome.^10,15,25,27

In GBS, many patients report pain, which can present as bilateral sciatica or as throbbing or aching in the large muscles of the upper legs, flanks, or back.28 This pain, which results from the demyelination of the sensory nerve fibers, can be severe.10

Patients with GBS may experience manifestations of autonomic nervous system dysfunction—for example, arrhythmias, hypotension or hypertension, urinary retention, cardiomyopathy, and paralytic ileus.^10,20 Dysautonomia often impedes patients’ progress in inpatient rehabilitation. Patients may have persistent problems involving postural hypotension, hypertension, excessive sympathetic outflow, or bladder and bowel dysfunction.²⁹

Blood pressure fluctuations, often attributed to changes in catecholamine levels and disturbances in the baroreceptor reflex pathway, are common and are considered characteristic of GBS. Transient or persistent hypotension is caused by the dysregulation of the parasympathetic and sympathetic systems, with subsequent alterations in venomotor tone.³ Additionally, an increased sensitivity to catecholamine can lead to cardiovascular disturbances, resulting in denervation hypersensitivity and impairment of the carotid sinus reflex.

Arrhythmias occur in perhaps half of patients with GBS. The most common is sustained sinus tachycardia, which usually requires no treatment. Bradycardia leading to atrioventricular blocks and asystole is believed to result from afferent baroreceptor reflex failure. Treatment may be required—either administration of atropine or insertion of a pacemaker, depending on the severity of the arrhythmia.^3,10

Myocardial involvement can range from asymptomatic mycocarditis to neurogenic stunned myocardium and heart failure. Patients with ECG abnormalities should undergo two-dimensional echocardiographic studies and other testing to explore cardiac involvement. Acute coronary syndromes, including ST-segment elevation MI, have been reported, in some cases associated with IVIG treatment. In one patient, coronary spasm was reported, with clean coronary arteries found on cardiac catheterization.³

Patients with GBS are at risk for compromised neuromuscular respiratory function; demyelination of the nerves that innervate the intercostal muscles and the diaphragm can result in respiratory failure. Key clinical indicators of respiratory muscle fatigue include tachypnea, diaphoresis, and asynchronous movements of the abdomen and chest;¹⁰ other symptoms relevant to respiratory or oropharyngeal weakness include slurred speech, dyspnea (with or without exertion), difficulty swallowing, and inability to cough.^2,10 Serial respiratory function testing is advisable to detect patients at risk for respiratory failure.³⁰

Diagnosis
Guillain-Barré is a syndrome diagnosed by a collection of symptoms (see Table 2^2,21,31), including subacute developing paralysis, symmetrical bilateral weakness beginning at onset, and diminishing to absent reflexes.^21,31 Other causes for rapidly developing weaknesses should be ruled out (see Table 3^10,21,26,31). Lumbar puncture typically shows increased protein levels with a normal white cell count; however, neither this test nor electrophysiologic evaluation offers significant value for diagnosis of GBS.^21,26,31

During the acute phase of GBS (within three weeks of onset), there is found an elevation of CSF protein (> 550 mg/L) without an elevation in white blood cells. This phenomenon, called albuminocytologic dissociation, reflects inflammation of the nerve roots and is considered the hallmark of GBS.²

MRI can also facilitate the diagnosis of GBS; it demonstrates anterior and posterior intrathecal spinal nerve roots and cauda equina.³² In patients with GBS, evidence supporting breakdown of the blood–nerve barrier can be seen in abnormal gadolinium enhancement of the intrathecal nerve roots on MRI.³³

When electrophysiologic studies are performed, they typically reveal slowing nerve conduction, prolonged distal latencies, and partial motor conduction block.³⁴ The characteristic finding of early demyelination is conduction block, a reduction in the amplitude of the muscle action potential after stimulation of the distal, as opposed to the proximal, nerve.²⁸ Nerve conduction studies may help in the diagnosis and classification of GBS—and, to a limited extent, formulation of a prognosis. Such alternative diagnoses as myositis and myasthenia gravis may be excluded by neurophysiology.²⁶ Early in GBS, neurophysiologic abnormalities may be very mild or occasionally normal; test results may not correlate with clinical disability.^35,36

The clinician cannot depend on clinical features alone to predict respiratory decline.³¹ Frequent evaluations of respiratory effort, by measurement of maximal inspiratory pressures and vital capacity, should be performed at the bedside to monitor diaphragmatic strength. Respiratory ventilation should be initiated if the patient becomes hypoxic or experiences a rapid decline in vital capacity (ie, below 60% of predicted value).¹⁰ Mechanical ventilation is more likely to be required in patients with a negative inspiratory force of less than 30 cm H2O.³¹

Treatment
Guillain-Barré syndrome has an acute onset and progression. Patients quickly become nonambulatory and may require total ventilation due to paralysis. Therapeutic options are IVIG or plasmapheresis (plasma exchange).^37-40 Corticosteroids do not appear to benefit patients with GBS.^41,42

Several mechanisms appear to contribute to the effectiveness of immunoglobulin.^38,39 Infused IVIG interferes with antigen presentation, inhibits antibody production, neutralizes pathologic autoantibodies, and modulates other immunologic events involved in the pathogenesis of autoimmune neuromuscular diseases, including GBS.⁴³ Adverse reactions, which are usually minor, include headache, fever, chills, myalgia, and malaise. In rare instances, anaphylaxis or renal failure may occur.^15,44

In plasmapheresis, blood is removed from the body and dialyzed, with circulating antibodies and immunoglobulins removed from the plasma; fresh frozen plasma, albumin, or saline is administered. This treatment, performed via central venous catheter, should be initiated as soon as possible after onset of symptoms but can be implemented as late as 30 days after GBS onset. Plasmapheresis requires personnel trained in dialysis, which may not be performed in all hospitals. Possible adverse events include infection and hemorrhage. Laboratory values must be monitored for hypokalemia and hypocalcemia.^45,46

Supportive Care
Patients with GBS require intensive care and very close monitoring for complications of respiratory difficulty and autonomic dysfunction. Individualized programs should be initiated for patients in the acute phase of GBS, aimed at the prevention of contractures and skin breakdown.¹⁰ Exercise programs, as conducted with the case patient, should also help relieve the fatigue syndromes that accompany GBS.

Immobilization associated with bed rest incurs a risk for pulmonary emboli and DVT; this has been found true during the first 12 weeks after symptom onset in patients with GBS who remain immobile.⁴⁷ The use of antiembolic hose and sequential compression devices can help reduce the risk for thrombotic events.¹⁰ Use of enoxaparin or heparin is recommended for nonambulating patients until they are able to walk, with Gaber et al⁴⁷ specifying the use of low-molecular-weight heparin to reduce, but not eliminate, the risk for DVT.

The pain associated with GBS can be severe. Narcotic analgesics may be administered with careful monitoring of autonomic denervation. Long-term management of neuropathic pain may require adjuvant therapy, such as tricyclic antidepressants, gabapentin, or tramadol hydrochloride.¹⁰ According to Pandey et al,⁴⁸ gabapentin alone may suffice for pain control in GBS, with minimal adverse effects. In certain rehabilitation facilities, tricyclic antidepressants, capsaicin, and transcutaneous nerve stimulation have been reported effective; during the early stages of treatment, until these treatments reach their full effect, pain medications such as tramadol or narcotics can provide temporary relief.²⁹

More than one-half of patients with GBS in the acute phase can develop ileus. Constipation can also occur as a result of pain medication use, prolonged bed rest, and poor intake. Auscultation of bowel sounds and abdominal assessment should be performed daily to monitor for ileus. Hughes et al¹⁰ do not recommend the use of promotility drugs in patients with dysautonomia.

After hospital discharge, easy fatigability can affect work and social activities. With continued physical therapy, occupational therapy, and monitoring, however, patients with GBS can expect to return to an optimal level of functioning. Speed of recovery varies with these patients from a few months to several years, depending on such factors as age and the extent to which axonal degeneration has occurred.^6,49

The Case Patient
For several weeks after discharge, the case patient continued to experience fatigue, low back pain, and general muscle pain. With her family’s support, she continued to receive outpatient physical therapy, and within one month she had regained her ankle strength. She was soon able to resume her classes, despite some lingering fatigue.

Conclusion
Guillain-Barré syndrome is a potentially life-threatening disease whose symptoms health care providers need to recognize quickly to provide prompt treatment. Supportive care for both patient and family is of key importance for maximum rehabilitation and return to the previous lifestyle. The clinical course of GBS is highly variable and difficult to predict. The patient’s outcome depends on several factors, including age and severity of illness. GBS patients can experience long-term psychosocial effects.

References
1. Magira EE, Papaioakim M, Nachamkin I, et al. Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP. J Immunol. 2003;170(6):3074-3080.

2. Tremblay ME, Closon A, D’Anjou G, Bussières JF. Guillain-Barré syndrome following H1N1 immunization in a pediatric patient. Ann Pharmacother. 2010;44(7-8):1330-1333.

3. Mukerji S, Aloka F, Farooq MU, et al. Cardiovascular complications of the Guillain-Barré syndrome. Am J Cardiol. 2009;104(10):1452-1455.

4. McGrogan A, Madle GC, Seaman HE, de Vries CS. The epidemiology of Guillain-Barré syndrome worldwide: a systematic literature review. Neuroepidemiology. 2009;32(2):150-163.

5. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009; 32(4):309-323.

6. van Doorn PA. What’s new in Guillain-Barré syndrome in 2007-2008? J Periph Nerv Syst. 2009;14(2):72-74.

7. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7(10):939-950.

8. Chiò A, Cocito D, Leone M, et al; Piemonte and alle d’Aosta Register for Guillain-Barré Syndrome. Guillain-Barré syndrome: a prospective, population-based incidence and outcome survey. Neurology. 2003; 60(7):1146-1150.

9. Hadden RD, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barré syndrome. Neurology. 2001;56(6):758-765.

10. Hughes RA, Wijdicks EF, Benson E, et al. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol. 2005;62(8):1194-1198.

11. Aluka KJ, Turner PL, Fullum TM. Guillain-Barré syndrome and postbariatric surgery polyneuropathies. JSLS. 2009;13(2):250-253.

12. Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barré syndrome. J Neurol Sci. 2003;208(1-2):39-42.

13. Lin WC, Lee PI, Lu CY, et al. Mycoplasma pneumoniae encephalitis in childhood. J Microbiol Immunol Infect. 2002;35(3):173-178.

14. Sivadon-Tardy V, Orlikowski D, Porcher R, et al. Detection of Campylobacter jejuni by culture and real-time PCR in a French cohort of patients with Guillain-Barre syndrome. J Clin Microbiol. 2010;48 (6):2278-2281.

15. van Doorn PA, Kuitwaard K, Walgaard C, et al. IVIG treatment and prognosis in Guillain-Barré syndrome. J Clin Immunol. 2010;30 suppl 1:S74-S78.

16. Kaida K, Kusunoki S. Guillan-Barré syndrome: update on immunobiology and treatment. Expert Rev Neurother. 2009;9(9):1307-1319.

17. Forsberg A, Press R, Einarsson U, et al. Disability and health-related quality of life in Guillain-Barré syndrome during the first two years after onset: a prospective study. Clin Rehabil. 2005;19(8):900-909.

18. Criteria for diagnosis of Guillain-Barré syndrome. Ann Neurol. 1978;3(6):565-566.

19. van Koningsveld R, Steyerberg EW, Hughes RA, et al. A clinical progostic scoring system for Guillain-Barré syndrome. Lancet Neurol. 2007;6(7):589-594.

20. Koeppen S, Kraywinkel K, Wessendorf TE, et al. Long-term outcome of Guillain-Barré syndrome. Neuro­crit Care. 2006;5(3)235-242.

21. Sheridan JM, Smith D. Atypical Guillain-Barré in the emergency department. West J Emerg Med. 2010;11(1):80-82.

22. Ogawara K, Kuwabara S, Koga M, et al. Anti-GM1b IgG antibody is associated with acute motor axonal neuropathy and Campylobacter jejuni infection. J Neurol Sci. 2003;210(1-2):41-45.

23. Nagashima T, Koga M, Odaka M, et al. Continuous spectrum of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. Arch Neurol. 2007;64(10):1519-1523.

24. Oh SJ, LaGanke C, Claussen GC. Sensory Guillain-Barré syndrome. Neurology. 2001;56(1):82-86.

25. Aráranyi Z, Kovács T, Sipos I, Bereczki D. Miller Fisher syndrome: brief overview and update with a focus on electrophysiological findings. Eur J Neurol. 2011 Jun 1. [Epub ahead of print]

26. Hughes RA, Cornblath, DR. Guillain-Barré syndrome. Lancet. 2005;366(9497):1653-1666.

27. Snyder LA, Rismondo V, Miller NR. The Fisher variant of Guillain-Barré syndrome (Fisher syndrome). J Neuroophthalmol. 2009;29(4):312-324.

28. Ropper AH. The Guillain-Barré syndrome. N Engl J Med.1992;326(17):1130-1136.

29. Meythaler JM. Rehabilitation of Guillain-Barré syndrome. Arch Phys Med Rehabil.1997;78(8):872-879.

30. Sharshar T, Chevret S, Bourdain F, et al; French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. Early predictors of mechanical ventilation in Guillain-Barré syndrome. Crit Care Med. 2003; 31(1):278-283.

31. McGillicuddy DC, Walker O, Shapiro NI, et al. Guillain-Barré syndrome in the emergency department. Ann Emerg Med. 2006;47(4):390-393.

32. Yikilmaz A, Doganay S, Gumus H, et al. Magnetic resonance imaging of childhood Guillain-Barré syndrome. Childs Nerv Syst. 2010;26(8):1103-1108.

33. Gonzalez-Quevedo A, Carriera RF, O’Farrill ZL, et al. An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain-Barré syndrome. Neurol India. 2009;57(3):288-294.

34. Abai S, Kim SB, Kim JP, Lim YJ. Guillan-Barré syndrome combined with acute cervical myelopathy. J Korean Neurosurg Soc. 2010;48(3):298-300.

35. Uncini A, Yuki N. Electrophysiologic and immunopathologic correlates in Guillain-Barré syndrome subtypes. Expert Rev Neurother. 2009;9(6):869-884.

36. Hadden RD, Hughes RA. Management of inflammatory neuropathies. J Neurol Neurosurg Psychiatry. 2003;74 suppl 2:ii9-ii14.

37. Raphaël JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2002;(2):CD001798.

38. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Jun 16; (6):CD002063.

39. Human immunoglobulin and the Guillain-Barré syndrome: new indication. An alternative to plasmapheresis. Prescrire Int. 2000;9(49):142-143.

40. van der Meché FG, Schmitz PI; Dutch Guillain-Barré Study Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med. 1992;327(17):1123-1129.

41. Hughes RA, Swan AV, van Doorn PA. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Feb 16;(2):CD001446.

42. Hahn AF. Guillain-Barré syndrome. Lancet. 1998; 352(9128):635-641.

43. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19):2367-2375.

44. Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokenetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol. 2009;66(5):597-603.

45. Atkinson SB, Carr RL, Maybee P, Haynes D. The challenges of managing and treating Guillain-Barré syndrome during the acute phase. Dimens Crit Care Nurs. 2006;25(6):256-263.

46. van Doorn PA. Treatment of Guillain-Barré syndrome and CIDP. J Periph Nerv Syst. 2005;10(2):113-127.

47. Gaber TA, Kirker SGB, Jenner JR. Current practice of prophylactic anticoagulation in Guillain-Barré syndrome. Clin Rehabil. 2002;16(2):190-193.

48. Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in Guillain-Barré syndrome: a double-blinded, placebo-controlled, crossover study. Anesth Analg. 2002;95(6):1719-1723.

49. de Vries JM, Hagemans ML, Bussmann JB, et al. Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease. Cell Mol Life Sci. 2010;67(5):701-713.

A 20-year-old woman presented to her primary care clinic with a chief complaint of lower leg weakness and difficulty walking. The weakness she described had been worsening over the previous four days, with progressively worsening tingling and numbness of her toes bilaterally.

The day before the patient presented, she noticed numbness and paresthesia in both calves. At the time of her presentation to the clinic, she complained of low back ache, paresthesia of both hands, numbness bilaterally to her groin, difficulty sitting upright, ataxia, and a numb, thick-feeling tongue. She denied fever, neck stiffness, shortness of breath, headache, or visual changes.

The patient stated that 10 days earlier, she had developed an upper respiratory infection for which she was seen at the clinic and treated with a seven-day course of amoxicillin/clavulanate 875/125 mg twice daily. She said that she had recovered completely.

A review of the patient’s systems revealed proximal muscle weakness bilaterally (2/5) and loss of touch-pressure in the lower extremities. She was experiencing paresthesia of the hands and mild weakness bilaterally (4/5). She also walked with an ataxic gait and had reduced deep tendon reflexes in the lower limbs. All cranial nerves were intact, and her vital signs were stable.

The woman’s medical history was positive only for asthma. Her family history included ischemic stroke in the maternal grandfather and brain tumor in the paternal grandfather. Social history was positive for alcohol intake (ranging from four to 12 beers per week). The patient said she had never smoked or used illicit drugs. She was an unmarried college student, living in a dorm on campus. She participated in track at school.

The patient was admitted to the hospital telemetry step-down unit, and a neurology consultation was requested. Tests were ordered, among them MRI of the head and spine and comprehensive blood work, to rule out neurologic, infectious, or metabolic causes of the patient’s weakness; urinalysis was also obtained. These tests all yielded negative results.

A lumbar puncture performed the following day revealed a cerebrospinal fluid (CSF) protein level of 570 mg/L (normal range, 150 to 450 mg/L). Leukocytes numbered 2 cells/mm³ (normal count, 0 to 10 cells/mm³).

Based on the patient’s presentation, history, and symptoms, a neurologist made a diagnosis of Guillain-Barré syndrome. It was decided that no electromyographic (EMG) study was required to rule out other disease processes (eg, spinal cord disease, multiple sclerosis, tumors).

The patient underwent a five-dose course of immunomodulatory therapy with IV immunoglobulin (IVIG). In the step-down unit, she experienced one incident of sinus bradycardia (ie, resting heart rate between 40 and 50 beats/min). Her blood pressure remained stable, as did her respiratory status, according to peak expiratory flow measured frequently at her bedside.

Physical therapy was initiated, consisting of passive and active range of motion, crossovers with the patient’s feet, and stair training. This was done in response to a complaint of ankle weakness, and it helped to strengthen weakened muscles and improve alignment while the patient was bedridden and in a weakened, fatigued state. Additionally, the patient was given enoxaparin, wore antiembolic hose, and used sequential compression devices while in bed. As a result of these measures, she never experienced a pulmonary embolus or deep vein thrombosis (DVT) as a result of being immobilized.

By the seventh day of hospitalization, the patient had stable vital signs and improved lower limb strength, and numbness was resolving in her hands and lower extremities. She was discharged to home, with physical therapy to resume on an outpatient basis.

Discussion
Guillain-Barré syndrome (GBS), an acute immune-mediated paralytic disorder,¹ manifests in the form of weakness and diminished reflexes. Affecting the peripheral nerves, GBS is characterized by progressive symmetrical ascending weakness with varying degrees of sensory complaints.^2,3

GBS occurs worldwide, and incidence is estimated between 1.1 and 1.8 cases per 100,000 persons.⁴ In the United States, GBS can be found in all age-groups, with peak incidence noted in elderly persons and young adults.^5,6 Even with treatment, 3% to 10% of patients are reported to die of this illness, and 20% cannot walk six months after symptom onset.⁷ In one prospective population-based study of patients with confirmed GBS, 6% of patients died within 30 days of symptom onset, often as a result of respiratory complications.⁸

GBS is a postinfectious disorder, with cases developing several days or weeks after a viral or bacterial illness—most commonly, an upper respiratory infection or diarrhea (see Table 1^9-13). The most common trigger of GBS is infection with the bacterial microorganism Campylobacter jejuni (occurring in 15% to 40% of patients with GBS),^9,14 a pathogen that can produce demyelination-causing antibodies. Other responsible pathogens include cytomegalovirus and Epstein-Barr virus.⁹ In a process called molecular mimicry, the immune system is unable to distinguish the amino acid of an infectious organism from the proteinaceous content of the peripheral nerve.¹⁵ Subsequently, the immune system attacks and destroys the myelin sheath.

An example of this is the apparent cross-reaction of the ganglioside GM1 with C jejuni lipopolysaccharide antigens.^14,15 The resulting effect is immunologic damage to the peripheral nervous system. The flaccid paralysis that occurs in patients with GBS is thought to be caused by lymphocytic infiltration and complement activation of the spinal roots and peripheral nerves, where macrophages strip the myelin.^5,15,16

Stages and Variants
Three stages characterize the course of GBS. The acute phase, which lasts one to four weeks, begins with onset of symptoms and persists until the associated neurologic deterioration has ceased. During the second phase, the plateau period, symptoms persist with no further deterioration; this stage can last several days to several weeks or months. The final phase, the recovery period, can last from four months to two years after symptom onset.^15,17,18

The clinical course of GBS is highly variable and in many cases difficult to predict. Certain factors have been associated with a poor outcome: advancing age, previous presence of diarrhea, need for mechanical ventilation, an extended plateau phase, and a lower patient score on the Erasmus GBS Outcome Scale,¹⁹ when measured two weeks after GBS onset.^8,20 This score can help predict the patient’s chance of independent walking after six months.^15,19

Although the classic presenting symptom of GBS is symmetric ascending weakness, several disease variants have been identified, with differing symptoms and degrees of recovery. These variants also differ in terms of the muscle groups affected; in some, visual defects may be present at onset. GBS variants include²¹:

• Acute motor axonal neuropathy (AMAN)^1,22

• Acute inflammatory demyelinating polyneuropathy (AIDP)¹

• Pharyngeal-cervical-brachial variant²³

• Purely sensory variant24

• Miller-Fisher syndrome, which manifests with ophthalmoplegia, in addition to ataxia and areflexia²⁵

• Axonal form.^5,21

AMAN and AIDP are the most common subtypes of GBS.¹

Symptoms, Signs, and Disease Manifestations
Limb weakness, the classic presenting symptom of GBS, is both symmetrical and ascending. Weakness can develop acutely and progress over days to weeks.^2,15 Hughes and Cornblath²⁶ also note pain, numbness, and paresthesias among the initial symptoms of GBS. Others include sensory changes, cranial nerve involvement, various autonomic changes, and respiratory or oropharyngeal weakness. Reflexes, particularly the tendon reflexes, may be diminished or absent.^15,18,21 In many cases, sensory changes (ie, pain) may precede the onset of weakness, often making diagnosis difficult.¹⁵

Cranial nerves most commonly affected are V, VI, VII, X, XI, and  XII, with manifestations that include dysphagia, dysarthria, diplopia, limitation to eye movements, and facial droop and weakness. Usually facial and oropharyngeal weakness occur after the extremities and trunk are affected. Blindness may occur if demyelination of the optic nerve occurs; this is seen in Miller-Fisher syndrome.^10,15,25,27

In GBS, many patients report pain, which can present as bilateral sciatica or as throbbing or aching in the large muscles of the upper legs, flanks, or back.28 This pain, which results from the demyelination of the sensory nerve fibers, can be severe.10

Patients with GBS may experience manifestations of autonomic nervous system dysfunction—for example, arrhythmias, hypotension or hypertension, urinary retention, cardiomyopathy, and paralytic ileus.^10,20 Dysautonomia often impedes patients’ progress in inpatient rehabilitation. Patients may have persistent problems involving postural hypotension, hypertension, excessive sympathetic outflow, or bladder and bowel dysfunction.²⁹

Blood pressure fluctuations, often attributed to changes in catecholamine levels and disturbances in the baroreceptor reflex pathway, are common and are considered characteristic of GBS. Transient or persistent hypotension is caused by the dysregulation of the parasympathetic and sympathetic systems, with subsequent alterations in venomotor tone.³ Additionally, an increased sensitivity to catecholamine can lead to cardiovascular disturbances, resulting in denervation hypersensitivity and impairment of the carotid sinus reflex.

Arrhythmias occur in perhaps half of patients with GBS. The most common is sustained sinus tachycardia, which usually requires no treatment. Bradycardia leading to atrioventricular blocks and asystole is believed to result from afferent baroreceptor reflex failure. Treatment may be required—either administration of atropine or insertion of a pacemaker, depending on the severity of the arrhythmia.^3,10

Myocardial involvement can range from asymptomatic mycocarditis to neurogenic stunned myocardium and heart failure. Patients with ECG abnormalities should undergo two-dimensional echocardiographic studies and other testing to explore cardiac involvement. Acute coronary syndromes, including ST-segment elevation MI, have been reported, in some cases associated with IVIG treatment. In one patient, coronary spasm was reported, with clean coronary arteries found on cardiac catheterization.³

Patients with GBS are at risk for compromised neuromuscular respiratory function; demyelination of the nerves that innervate the intercostal muscles and the diaphragm can result in respiratory failure. Key clinical indicators of respiratory muscle fatigue include tachypnea, diaphoresis, and asynchronous movements of the abdomen and chest;¹⁰ other symptoms relevant to respiratory or oropharyngeal weakness include slurred speech, dyspnea (with or without exertion), difficulty swallowing, and inability to cough.^2,10 Serial respiratory function testing is advisable to detect patients at risk for respiratory failure.³⁰

Diagnosis
Guillain-Barré is a syndrome diagnosed by a collection of symptoms (see Table 2^2,21,31), including subacute developing paralysis, symmetrical bilateral weakness beginning at onset, and diminishing to absent reflexes.^21,31 Other causes for rapidly developing weaknesses should be ruled out (see Table 3^10,21,26,31). Lumbar puncture typically shows increased protein levels with a normal white cell count; however, neither this test nor electrophysiologic evaluation offers significant value for diagnosis of GBS.^21,26,31

During the acute phase of GBS (within three weeks of onset), there is found an elevation of CSF protein (> 550 mg/L) without an elevation in white blood cells. This phenomenon, called albuminocytologic dissociation, reflects inflammation of the nerve roots and is considered the hallmark of GBS.²

MRI can also facilitate the diagnosis of GBS; it demonstrates anterior and posterior intrathecal spinal nerve roots and cauda equina.³² In patients with GBS, evidence supporting breakdown of the blood–nerve barrier can be seen in abnormal gadolinium enhancement of the intrathecal nerve roots on MRI.³³

When electrophysiologic studies are performed, they typically reveal slowing nerve conduction, prolonged distal latencies, and partial motor conduction block.³⁴ The characteristic finding of early demyelination is conduction block, a reduction in the amplitude of the muscle action potential after stimulation of the distal, as opposed to the proximal, nerve.²⁸ Nerve conduction studies may help in the diagnosis and classification of GBS—and, to a limited extent, formulation of a prognosis. Such alternative diagnoses as myositis and myasthenia gravis may be excluded by neurophysiology.²⁶ Early in GBS, neurophysiologic abnormalities may be very mild or occasionally normal; test results may not correlate with clinical disability.^35,36

The clinician cannot depend on clinical features alone to predict respiratory decline.³¹ Frequent evaluations of respiratory effort, by measurement of maximal inspiratory pressures and vital capacity, should be performed at the bedside to monitor diaphragmatic strength. Respiratory ventilation should be initiated if the patient becomes hypoxic or experiences a rapid decline in vital capacity (ie, below 60% of predicted value).¹⁰ Mechanical ventilation is more likely to be required in patients with a negative inspiratory force of less than 30 cm H2O.³¹

Treatment
Guillain-Barré syndrome has an acute onset and progression. Patients quickly become nonambulatory and may require total ventilation due to paralysis. Therapeutic options are IVIG or plasmapheresis (plasma exchange).^37-40 Corticosteroids do not appear to benefit patients with GBS.^41,42

Several mechanisms appear to contribute to the effectiveness of immunoglobulin.^38,39 Infused IVIG interferes with antigen presentation, inhibits antibody production, neutralizes pathologic autoantibodies, and modulates other immunologic events involved in the pathogenesis of autoimmune neuromuscular diseases, including GBS.⁴³ Adverse reactions, which are usually minor, include headache, fever, chills, myalgia, and malaise. In rare instances, anaphylaxis or renal failure may occur.^15,44

In plasmapheresis, blood is removed from the body and dialyzed, with circulating antibodies and immunoglobulins removed from the plasma; fresh frozen plasma, albumin, or saline is administered. This treatment, performed via central venous catheter, should be initiated as soon as possible after onset of symptoms but can be implemented as late as 30 days after GBS onset. Plasmapheresis requires personnel trained in dialysis, which may not be performed in all hospitals. Possible adverse events include infection and hemorrhage. Laboratory values must be monitored for hypokalemia and hypocalcemia.^45,46

Supportive Care
Patients with GBS require intensive care and very close monitoring for complications of respiratory difficulty and autonomic dysfunction. Individualized programs should be initiated for patients in the acute phase of GBS, aimed at the prevention of contractures and skin breakdown.¹⁰ Exercise programs, as conducted with the case patient, should also help relieve the fatigue syndromes that accompany GBS.

Immobilization associated with bed rest incurs a risk for pulmonary emboli and DVT; this has been found true during the first 12 weeks after symptom onset in patients with GBS who remain immobile.⁴⁷ The use of antiembolic hose and sequential compression devices can help reduce the risk for thrombotic events.¹⁰ Use of enoxaparin or heparin is recommended for nonambulating patients until they are able to walk, with Gaber et al⁴⁷ specifying the use of low-molecular-weight heparin to reduce, but not eliminate, the risk for DVT.

The pain associated with GBS can be severe. Narcotic analgesics may be administered with careful monitoring of autonomic denervation. Long-term management of neuropathic pain may require adjuvant therapy, such as tricyclic antidepressants, gabapentin, or tramadol hydrochloride.¹⁰ According to Pandey et al,⁴⁸ gabapentin alone may suffice for pain control in GBS, with minimal adverse effects. In certain rehabilitation facilities, tricyclic antidepressants, capsaicin, and transcutaneous nerve stimulation have been reported effective; during the early stages of treatment, until these treatments reach their full effect, pain medications such as tramadol or narcotics can provide temporary relief.²⁹

More than one-half of patients with GBS in the acute phase can develop ileus. Constipation can also occur as a result of pain medication use, prolonged bed rest, and poor intake. Auscultation of bowel sounds and abdominal assessment should be performed daily to monitor for ileus. Hughes et al¹⁰ do not recommend the use of promotility drugs in patients with dysautonomia.

After hospital discharge, easy fatigability can affect work and social activities. With continued physical therapy, occupational therapy, and monitoring, however, patients with GBS can expect to return to an optimal level of functioning. Speed of recovery varies with these patients from a few months to several years, depending on such factors as age and the extent to which axonal degeneration has occurred.^6,49

The Case Patient
For several weeks after discharge, the case patient continued to experience fatigue, low back pain, and general muscle pain. With her family’s support, she continued to receive outpatient physical therapy, and within one month she had regained her ankle strength. She was soon able to resume her classes, despite some lingering fatigue.

Conclusion
Guillain-Barré syndrome is a potentially life-threatening disease whose symptoms health care providers need to recognize quickly to provide prompt treatment. Supportive care for both patient and family is of key importance for maximum rehabilitation and return to the previous lifestyle. The clinical course of GBS is highly variable and difficult to predict. The patient’s outcome depends on several factors, including age and severity of illness. GBS patients can experience long-term psychosocial effects.

References
1. Magira EE, Papaioakim M, Nachamkin I, et al. Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP. J Immunol. 2003;170(6):3074-3080.

2. Tremblay ME, Closon A, D’Anjou G, Bussières JF. Guillain-Barré syndrome following H1N1 immunization in a pediatric patient. Ann Pharmacother. 2010;44(7-8):1330-1333.

3. Mukerji S, Aloka F, Farooq MU, et al. Cardiovascular complications of the Guillain-Barré syndrome. Am J Cardiol. 2009;104(10):1452-1455.

4. McGrogan A, Madle GC, Seaman HE, de Vries CS. The epidemiology of Guillain-Barré syndrome worldwide: a systematic literature review. Neuroepidemiology. 2009;32(2):150-163.

5. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009; 32(4):309-323.

6. van Doorn PA. What’s new in Guillain-Barré syndrome in 2007-2008? J Periph Nerv Syst. 2009;14(2):72-74.

7. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7(10):939-950.

8. Chiò A, Cocito D, Leone M, et al; Piemonte and alle d’Aosta Register for Guillain-Barré Syndrome. Guillain-Barré syndrome: a prospective, population-based incidence and outcome survey. Neurology. 2003; 60(7):1146-1150.

9. Hadden RD, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barré syndrome. Neurology. 2001;56(6):758-765.

10. Hughes RA, Wijdicks EF, Benson E, et al. Supportive care for patients with Guillain-Barré syndrome. Arch Neurol. 2005;62(8):1194-1198.

11. Aluka KJ, Turner PL, Fullum TM. Guillain-Barré syndrome and postbariatric surgery polyneuropathies. JSLS. 2009;13(2):250-253.

12. Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barré syndrome. J Neurol Sci. 2003;208(1-2):39-42.

13. Lin WC, Lee PI, Lu CY, et al. Mycoplasma pneumoniae encephalitis in childhood. J Microbiol Immunol Infect. 2002;35(3):173-178.

14. Sivadon-Tardy V, Orlikowski D, Porcher R, et al. Detection of Campylobacter jejuni by culture and real-time PCR in a French cohort of patients with Guillain-Barre syndrome. J Clin Microbiol. 2010;48 (6):2278-2281.

15. van Doorn PA, Kuitwaard K, Walgaard C, et al. IVIG treatment and prognosis in Guillain-Barré syndrome. J Clin Immunol. 2010;30 suppl 1:S74-S78.

16. Kaida K, Kusunoki S. Guillan-Barré syndrome: update on immunobiology and treatment. Expert Rev Neurother. 2009;9(9):1307-1319.

17. Forsberg A, Press R, Einarsson U, et al. Disability and health-related quality of life in Guillain-Barré syndrome during the first two years after onset: a prospective study. Clin Rehabil. 2005;19(8):900-909.

18. Criteria for diagnosis of Guillain-Barré syndrome. Ann Neurol. 1978;3(6):565-566.

19. van Koningsveld R, Steyerberg EW, Hughes RA, et al. A clinical progostic scoring system for Guillain-Barré syndrome. Lancet Neurol. 2007;6(7):589-594.

20. Koeppen S, Kraywinkel K, Wessendorf TE, et al. Long-term outcome of Guillain-Barré syndrome. Neuro­crit Care. 2006;5(3)235-242.

21. Sheridan JM, Smith D. Atypical Guillain-Barré in the emergency department. West J Emerg Med. 2010;11(1):80-82.

22. Ogawara K, Kuwabara S, Koga M, et al. Anti-GM1b IgG antibody is associated with acute motor axonal neuropathy and Campylobacter jejuni infection. J Neurol Sci. 2003;210(1-2):41-45.

23. Nagashima T, Koga M, Odaka M, et al. Continuous spectrum of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. Arch Neurol. 2007;64(10):1519-1523.

24. Oh SJ, LaGanke C, Claussen GC. Sensory Guillain-Barré syndrome. Neurology. 2001;56(1):82-86.

25. Aráranyi Z, Kovács T, Sipos I, Bereczki D. Miller Fisher syndrome: brief overview and update with a focus on electrophysiological findings. Eur J Neurol. 2011 Jun 1. [Epub ahead of print]

26. Hughes RA, Cornblath, DR. Guillain-Barré syndrome. Lancet. 2005;366(9497):1653-1666.

27. Snyder LA, Rismondo V, Miller NR. The Fisher variant of Guillain-Barré syndrome (Fisher syndrome). J Neuroophthalmol. 2009;29(4):312-324.

28. Ropper AH. The Guillain-Barré syndrome. N Engl J Med.1992;326(17):1130-1136.

29. Meythaler JM. Rehabilitation of Guillain-Barré syndrome. Arch Phys Med Rehabil.1997;78(8):872-879.

30. Sharshar T, Chevret S, Bourdain F, et al; French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. Early predictors of mechanical ventilation in Guillain-Barré syndrome. Crit Care Med. 2003; 31(1):278-283.

31. McGillicuddy DC, Walker O, Shapiro NI, et al. Guillain-Barré syndrome in the emergency department. Ann Emerg Med. 2006;47(4):390-393.

32. Yikilmaz A, Doganay S, Gumus H, et al. Magnetic resonance imaging of childhood Guillain-Barré syndrome. Childs Nerv Syst. 2010;26(8):1103-1108.

33. Gonzalez-Quevedo A, Carriera RF, O’Farrill ZL, et al. An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain-Barré syndrome. Neurol India. 2009;57(3):288-294.

34. Abai S, Kim SB, Kim JP, Lim YJ. Guillan-Barré syndrome combined with acute cervical myelopathy. J Korean Neurosurg Soc. 2010;48(3):298-300.

35. Uncini A, Yuki N. Electrophysiologic and immunopathologic correlates in Guillain-Barré syndrome subtypes. Expert Rev Neurother. 2009;9(6):869-884.

36. Hadden RD, Hughes RA. Management of inflammatory neuropathies. J Neurol Neurosurg Psychiatry. 2003;74 suppl 2:ii9-ii14.

37. Raphaël JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2002;(2):CD001798.

38. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Jun 16; (6):CD002063.

39. Human immunoglobulin and the Guillain-Barré syndrome: new indication. An alternative to plasmapheresis. Prescrire Int. 2000;9(49):142-143.

40. van der Meché FG, Schmitz PI; Dutch Guillain-Barré Study Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med. 1992;327(17):1123-1129.

41. Hughes RA, Swan AV, van Doorn PA. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2010 Feb 16;(2):CD001446.

42. Hahn AF. Guillain-Barré syndrome. Lancet. 1998; 352(9128):635-641.

43. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19):2367-2375.

44. Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokenetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol. 2009;66(5):597-603.

45. Atkinson SB, Carr RL, Maybee P, Haynes D. The challenges of managing and treating Guillain-Barré syndrome during the acute phase. Dimens Crit Care Nurs. 2006;25(6):256-263.

46. van Doorn PA. Treatment of Guillain-Barré syndrome and CIDP. J Periph Nerv Syst. 2005;10(2):113-127.

47. Gaber TA, Kirker SGB, Jenner JR. Current practice of prophylactic anticoagulation in Guillain-Barré syndrome. Clin Rehabil. 2002;16(2):190-193.

48. Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in Guillain-Barré syndrome: a double-blinded, placebo-controlled, crossover study. Anesth Analg. 2002;95(6):1719-1723.

49. de Vries JM, Hagemans ML, Bussmann JB, et al. Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease. Cell Mol Life Sci. 2010;67(5):701-713.

Missed dissecting aortic aneurysm proves fatal

A 43-YEAR-OLD MAN was admitted to the hospital complaining of severe chest pain, shortness of breath, sweating, and dry mouth. After being seen by several physicians, the patient suffered an aortic dissection, which caused bleeding in the wall of the aorta, an aortic rupture, and bleeding into the pericardium. He died 2 days later.

PLAINTIFF’S CLAIM The defendants failed to order tests to rule out a dissecting aortic aneurysm and did not include aortic dissection in the differential diagnosis. They failed to provide appropriate drug therapy to decrease cardiac impulse and lower the systolic blood pressure. They did not obtain an emergency cardiac consultation or admit the patient to a cardiovascular surgical intensive care unit.

THE DEFENSE The defendants denied negligence and claimed that nothing they did or failed to do contributed to the patient’s death.

VERDICT $250,000 Michigan settlement.

COMMENT Just yesterday, a malpractice lawyer presented me with a case very similar to this one: a patient with unexplained chest pain who died of a dissecting aneurysm. Remember, not all chest pain is caused by coronary artery disease.

Too-late cancer Dx blamed on neglected x-ray findings

A LONG-TERM CIGARETTE SMOKER IN HER 50s saw a physician in 2001 for symptoms of pneumonia. The doctor prescribed antibiotics and referred her to another facility for a chest radiograph.

Five days later, she returned to the physician’s office, where she was seen by another internist in the practice. The internist noted that the chest radiograph showed parenchymal densities in the right lung. Parenchymal densities had also showed up on 2 previous chest radiographs, but were more prevalent on the latest film. The internist advised the patient to finish her antibiotic regimen; he did not prescribe further tests or treatment.

Over the following 40 months, doctors in the patient’s medical group examined her 8 times. Each time she complained of impaired respiration. The internist believed that the symptoms were caused by asthma.

In 2004, the patient was diagnosed with stage IV cancer of the right lung, which had spread to her bones and was untreatable. She died several weeks later.

PLAINTIFF’S CLAIM A proper diagnosis in 2001 would have allowed the cancer to be cured. A computed tomography scan should have been performed and a pulmonologist consulted at that time.

THE DEFENSE Findings from the radiograph from 2001 did not necessitate further action. Because the patient’s cancer had metastasized before that radiograph, treatment then (or later) would not have changed the outcome.

VERDICT $850,000 New York verdict.

COMMENT Careful follow-up and diagnosis of chest radiograph abnormalities is paramount.

Yes, it was a stroke

WEAKNESS, NUMBNESS, AND TINGLING IN HIS RIGHT ARM prompted a 56-year-old man to visit his primary care physician. The physician sent the patient to the emergency department (ED) for testing because he believed the man was experiencing stroke-like symptoms. As the patient and his wife drove to the hospital, the physician faxed the patient’s medical records to the ED.

When the patient’s wife tried to give ED employees the physician’s orders for tests and tell them of the doctor’s concern about a stroke, they told her that all the beds were full and she should sit down and wait.

The patient was eventually evaluated as a low-priority patient with numbness in his right hand. The examining doctor ordered radiographs of the right wrist and discharged the patient with a diagnosis of carpal tunnel syndrome.

Twenty minutes later, a nurse left a message telling the patient to return to the hospital for the stroke-related tests that had been ordered by his primary care physician. An ED physician other than the one who first examined the patient performed the tests—except for a test of blood flow to the brain. The physician diagnosed stroke-like symptoms and requested a consultation with another physician, which never happened. The patient was discharged about 6 hours after his first discharge.

About 16 hours later, the patient suffered a stroke. Subsequent testing revealed an obstruction in the left carotid artery. The stroke resulted in permanent neurologic injury.

PLAINTIFF’S CLAIM No information about the plaintiff’s claim is available.

THE DEFENSE The defendants denied negligence and disputed the extent of the patient’s injuries.

VERDICT $1.123 million Maryland verdict.

COMMENT Coordination of care remains critical, particularly between our outpatient offices and the busy ED.

Missed dissecting aortic aneurysm proves fatal

A 43-YEAR-OLD MAN was admitted to the hospital complaining of severe chest pain, shortness of breath, sweating, and dry mouth. After being seen by several physicians, the patient suffered an aortic dissection, which caused bleeding in the wall of the aorta, an aortic rupture, and bleeding into the pericardium. He died 2 days later.

PLAINTIFF’S CLAIM The defendants failed to order tests to rule out a dissecting aortic aneurysm and did not include aortic dissection in the differential diagnosis. They failed to provide appropriate drug therapy to decrease cardiac impulse and lower the systolic blood pressure. They did not obtain an emergency cardiac consultation or admit the patient to a cardiovascular surgical intensive care unit.

THE DEFENSE The defendants denied negligence and claimed that nothing they did or failed to do contributed to the patient’s death.

VERDICT $250,000 Michigan settlement.

COMMENT Just yesterday, a malpractice lawyer presented me with a case very similar to this one: a patient with unexplained chest pain who died of a dissecting aneurysm. Remember, not all chest pain is caused by coronary artery disease.

Too-late cancer Dx blamed on neglected x-ray findings

A LONG-TERM CIGARETTE SMOKER IN HER 50s saw a physician in 2001 for symptoms of pneumonia. The doctor prescribed antibiotics and referred her to another facility for a chest radiograph.

Five days later, she returned to the physician’s office, where she was seen by another internist in the practice. The internist noted that the chest radiograph showed parenchymal densities in the right lung. Parenchymal densities had also showed up on 2 previous chest radiographs, but were more prevalent on the latest film. The internist advised the patient to finish her antibiotic regimen; he did not prescribe further tests or treatment.

Over the following 40 months, doctors in the patient’s medical group examined her 8 times. Each time she complained of impaired respiration. The internist believed that the symptoms were caused by asthma.

In 2004, the patient was diagnosed with stage IV cancer of the right lung, which had spread to her bones and was untreatable. She died several weeks later.

PLAINTIFF’S CLAIM A proper diagnosis in 2001 would have allowed the cancer to be cured. A computed tomography scan should have been performed and a pulmonologist consulted at that time.

THE DEFENSE Findings from the radiograph from 2001 did not necessitate further action. Because the patient’s cancer had metastasized before that radiograph, treatment then (or later) would not have changed the outcome.

VERDICT $850,000 New York verdict.

COMMENT Careful follow-up and diagnosis of chest radiograph abnormalities is paramount.

Yes, it was a stroke

WEAKNESS, NUMBNESS, AND TINGLING IN HIS RIGHT ARM prompted a 56-year-old man to visit his primary care physician. The physician sent the patient to the emergency department (ED) for testing because he believed the man was experiencing stroke-like symptoms. As the patient and his wife drove to the hospital, the physician faxed the patient’s medical records to the ED.

When the patient’s wife tried to give ED employees the physician’s orders for tests and tell them of the doctor’s concern about a stroke, they told her that all the beds were full and she should sit down and wait.

The patient was eventually evaluated as a low-priority patient with numbness in his right hand. The examining doctor ordered radiographs of the right wrist and discharged the patient with a diagnosis of carpal tunnel syndrome.

Twenty minutes later, a nurse left a message telling the patient to return to the hospital for the stroke-related tests that had been ordered by his primary care physician. An ED physician other than the one who first examined the patient performed the tests—except for a test of blood flow to the brain. The physician diagnosed stroke-like symptoms and requested a consultation with another physician, which never happened. The patient was discharged about 6 hours after his first discharge.

About 16 hours later, the patient suffered a stroke. Subsequent testing revealed an obstruction in the left carotid artery. The stroke resulted in permanent neurologic injury.

PLAINTIFF’S CLAIM No information about the plaintiff’s claim is available.

THE DEFENSE The defendants denied negligence and disputed the extent of the patient’s injuries.

VERDICT $1.123 million Maryland verdict.

COMMENT Coordination of care remains critical, particularly between our outpatient offices and the busy ED.

Missed dissecting aortic aneurysm proves fatal

A 43-YEAR-OLD MAN was admitted to the hospital complaining of severe chest pain, shortness of breath, sweating, and dry mouth. After being seen by several physicians, the patient suffered an aortic dissection, which caused bleeding in the wall of the aorta, an aortic rupture, and bleeding into the pericardium. He died 2 days later.

PLAINTIFF’S CLAIM The defendants failed to order tests to rule out a dissecting aortic aneurysm and did not include aortic dissection in the differential diagnosis. They failed to provide appropriate drug therapy to decrease cardiac impulse and lower the systolic blood pressure. They did not obtain an emergency cardiac consultation or admit the patient to a cardiovascular surgical intensive care unit.

THE DEFENSE The defendants denied negligence and claimed that nothing they did or failed to do contributed to the patient’s death.

VERDICT $250,000 Michigan settlement.

COMMENT Just yesterday, a malpractice lawyer presented me with a case very similar to this one: a patient with unexplained chest pain who died of a dissecting aneurysm. Remember, not all chest pain is caused by coronary artery disease.

Too-late cancer Dx blamed on neglected x-ray findings

A LONG-TERM CIGARETTE SMOKER IN HER 50s saw a physician in 2001 for symptoms of pneumonia. The doctor prescribed antibiotics and referred her to another facility for a chest radiograph.

Five days later, she returned to the physician’s office, where she was seen by another internist in the practice. The internist noted that the chest radiograph showed parenchymal densities in the right lung. Parenchymal densities had also showed up on 2 previous chest radiographs, but were more prevalent on the latest film. The internist advised the patient to finish her antibiotic regimen; he did not prescribe further tests or treatment.

Over the following 40 months, doctors in the patient’s medical group examined her 8 times. Each time she complained of impaired respiration. The internist believed that the symptoms were caused by asthma.

In 2004, the patient was diagnosed with stage IV cancer of the right lung, which had spread to her bones and was untreatable. She died several weeks later.

PLAINTIFF’S CLAIM A proper diagnosis in 2001 would have allowed the cancer to be cured. A computed tomography scan should have been performed and a pulmonologist consulted at that time.

THE DEFENSE Findings from the radiograph from 2001 did not necessitate further action. Because the patient’s cancer had metastasized before that radiograph, treatment then (or later) would not have changed the outcome.

VERDICT $850,000 New York verdict.

COMMENT Careful follow-up and diagnosis of chest radiograph abnormalities is paramount.

Yes, it was a stroke

WEAKNESS, NUMBNESS, AND TINGLING IN HIS RIGHT ARM prompted a 56-year-old man to visit his primary care physician. The physician sent the patient to the emergency department (ED) for testing because he believed the man was experiencing stroke-like symptoms. As the patient and his wife drove to the hospital, the physician faxed the patient’s medical records to the ED.

When the patient’s wife tried to give ED employees the physician’s orders for tests and tell them of the doctor’s concern about a stroke, they told her that all the beds were full and she should sit down and wait.

The patient was eventually evaluated as a low-priority patient with numbness in his right hand. The examining doctor ordered radiographs of the right wrist and discharged the patient with a diagnosis of carpal tunnel syndrome.

Twenty minutes later, a nurse left a message telling the patient to return to the hospital for the stroke-related tests that had been ordered by his primary care physician. An ED physician other than the one who first examined the patient performed the tests—except for a test of blood flow to the brain. The physician diagnosed stroke-like symptoms and requested a consultation with another physician, which never happened. The patient was discharged about 6 hours after his first discharge.

About 16 hours later, the patient suffered a stroke. Subsequent testing revealed an obstruction in the left carotid artery. The stroke resulted in permanent neurologic injury.

PLAINTIFF’S CLAIM No information about the plaintiff’s claim is available.

THE DEFENSE The defendants denied negligence and disputed the extent of the patient’s injuries.

VERDICT $1.123 million Maryland verdict.

COMMENT Coordination of care remains critical, particularly between our outpatient offices and the busy ED.

Nearly 3 out of 4 (71.9%) US women (and 72.6% of men) ages 60 to 79 years have cardiovascular disease (CVD)—the leading cause of death despite marked improvement in mortality rates in the last 4 decades. In that same age group, the prevalence of cerebral vascular disease is 8.2% in women and 7.2% in men.¹

The age-adjusted death rate for all adults is 135.1 in 100,000 for coronary heart disease (CHD) and 44.1 in 100,000 for cerebral vascular disease. In 2007, CVD caused 34.5% of deaths in women and 32.7% of deaths in men.¹

Evidence that CVD frequently manifests differently in women than in men led the American Heart Association (AHA) to issue recommendations for the prevention of CVD in women in 1999, and to follow with guidelines in 2004 and an update in 2007.^2-4 However, the recommended interventions were, with a few exceptions, the same as the recommendations for men. But that’s changed.

The latest update of the guidelines, published earlier this year, focuses more on sex-based differences, with the addition of pregnancy complications as a major risk factor, for example. (See “AHA’s 2011 CVD guideline update: What’s new?”.) Highlights of the guidelines,⁵ including the recommended interventions for all women (TABLE 1) and a comparison of its recommendations with those of the US Preventive Services Task Force (USPSTF)⁶ (TABLE 2)—are detailed here.

TABLE 1
AHA recommends these interventions for all women⁵

TABLE 2
CVD prevention in women: Comparing AHA¹and USPSTF recommendations^5,6

The AHA’s assessment of risk

The new guideline update recommends assessing each woman’s CVD risk and placing her into one of 3 risk groups—high risk, at risk, and ideal cardiovascular health (TABLE 3)—then using an algorithm to determine which preventive interventions to recommend based on her risk level.

This classification approach is challenging, for several reasons. It lumps women with markedly different risk profiles into the “at risk” group, a category that will likely apply to a high proportion of women. It also appears to encourage the use of diagnostic tests for subclinical vascular disease, for which there is no evidence of effectiveness. In addition, some of the terms used in the at-risk criteria, such as ”physical inactivity” and “poor diet,” are vague.

TABLE 3
Cardiovascular disease: How the AHA classifies women’s risk⁵

Some recommendations apply to all women, regardless of risk
The AHA recommendations for all women (TABLE 1) include smoking prevention or cessation, maintenance of optimal weight, regular physical activity, and a diet aimed at preventing CVD. The guidelines also emphasize that major CVD risks should be controlled, with either lifestyle and diet modifications (preferably) or pharmacotherapy. The aggressiveness of control targets depends on the level of risk and the presence of other risk factors.

The guidelines recommend against some interventions that are often used for CVD prevention, based on a high level of evidence that they are ineffective. These include estrogen or selective estrogen receptor modulators, antioxidant vitamins (vitamins E and C, and beta-carotene), folic acid with or without vitamins B6 and B12, and aspirin (for CHD prevention) for healthy women <65 years old.

The AHA does not take a position for or against several diagnostic and risk classification tools because of a lack of evidence of usefulness. These include CVD risk biomarkers such as high sensitivity C-reactive protein and imaging technologies such as coronary calcium scoring assessment.

AHA and USPSTF diverge, but not by much

Screening for conditions that increase CVD risk is not explicitly addressed in the AHA guidelines. Screening is implied by the proposed classification scheme, which includes the presence or absence of smoking, obesity, diabetes, hypertension, and dyslipidemia, but there is no guidance on when to start or stop screening for these conditions. The AHA and the USPSTF diverge on screening women for dyslipidemia, with the USPSTF recommending screening for lipid disorders only in women at increased risk for CHD.

The recommendations for optimal weight and activity levels in the AHA guidelines do not include advice on how to achieve them, nor do they call for an assessment of the effectiveness of behavioral counseling in the clinical setting. Because the USPSTF includes an assessment of, and recommendations for, asymptomatic patients in primary care settings, its recommendations do not address women with conditions such as established CVD, heart failure, or atrial fibrillation—which the AHA guidelines do.

Overall, the AHA and USPSTF agree more than they disagree, and each covers some areas that the other does not (TABLE 2). Family physicians can use the information provided by both entities to ensure that their female patients receive high-quality preventive care that will minimize their risk for CVD.

Nearly 3 out of 4 (71.9%) US women (and 72.6% of men) ages 60 to 79 years have cardiovascular disease (CVD)—the leading cause of death despite marked improvement in mortality rates in the last 4 decades. In that same age group, the prevalence of cerebral vascular disease is 8.2% in women and 7.2% in men.¹

The age-adjusted death rate for all adults is 135.1 in 100,000 for coronary heart disease (CHD) and 44.1 in 100,000 for cerebral vascular disease. In 2007, CVD caused 34.5% of deaths in women and 32.7% of deaths in men.¹

Evidence that CVD frequently manifests differently in women than in men led the American Heart Association (AHA) to issue recommendations for the prevention of CVD in women in 1999, and to follow with guidelines in 2004 and an update in 2007.^2-4 However, the recommended interventions were, with a few exceptions, the same as the recommendations for men. But that’s changed.

The latest update of the guidelines, published earlier this year, focuses more on sex-based differences, with the addition of pregnancy complications as a major risk factor, for example. (See “AHA’s 2011 CVD guideline update: What’s new?”.) Highlights of the guidelines,⁵ including the recommended interventions for all women (TABLE 1) and a comparison of its recommendations with those of the US Preventive Services Task Force (USPSTF)⁶ (TABLE 2)—are detailed here.

TABLE 1
AHA recommends these interventions for all women⁵

TABLE 2
CVD prevention in women: Comparing AHA¹and USPSTF recommendations^5,6

The AHA’s assessment of risk

The new guideline update recommends assessing each woman’s CVD risk and placing her into one of 3 risk groups—high risk, at risk, and ideal cardiovascular health (TABLE 3)—then using an algorithm to determine which preventive interventions to recommend based on her risk level.

This classification approach is challenging, for several reasons. It lumps women with markedly different risk profiles into the “at risk” group, a category that will likely apply to a high proportion of women. It also appears to encourage the use of diagnostic tests for subclinical vascular disease, for which there is no evidence of effectiveness. In addition, some of the terms used in the at-risk criteria, such as ”physical inactivity” and “poor diet,” are vague.

TABLE 3
Cardiovascular disease: How the AHA classifies women’s risk⁵

Some recommendations apply to all women, regardless of risk
The AHA recommendations for all women (TABLE 1) include smoking prevention or cessation, maintenance of optimal weight, regular physical activity, and a diet aimed at preventing CVD. The guidelines also emphasize that major CVD risks should be controlled, with either lifestyle and diet modifications (preferably) or pharmacotherapy. The aggressiveness of control targets depends on the level of risk and the presence of other risk factors.

The guidelines recommend against some interventions that are often used for CVD prevention, based on a high level of evidence that they are ineffective. These include estrogen or selective estrogen receptor modulators, antioxidant vitamins (vitamins E and C, and beta-carotene), folic acid with or without vitamins B6 and B12, and aspirin (for CHD prevention) for healthy women <65 years old.

The AHA does not take a position for or against several diagnostic and risk classification tools because of a lack of evidence of usefulness. These include CVD risk biomarkers such as high sensitivity C-reactive protein and imaging technologies such as coronary calcium scoring assessment.

AHA and USPSTF diverge, but not by much

Screening for conditions that increase CVD risk is not explicitly addressed in the AHA guidelines. Screening is implied by the proposed classification scheme, which includes the presence or absence of smoking, obesity, diabetes, hypertension, and dyslipidemia, but there is no guidance on when to start or stop screening for these conditions. The AHA and the USPSTF diverge on screening women for dyslipidemia, with the USPSTF recommending screening for lipid disorders only in women at increased risk for CHD.

The recommendations for optimal weight and activity levels in the AHA guidelines do not include advice on how to achieve them, nor do they call for an assessment of the effectiveness of behavioral counseling in the clinical setting. Because the USPSTF includes an assessment of, and recommendations for, asymptomatic patients in primary care settings, its recommendations do not address women with conditions such as established CVD, heart failure, or atrial fibrillation—which the AHA guidelines do.

Overall, the AHA and USPSTF agree more than they disagree, and each covers some areas that the other does not (TABLE 2). Family physicians can use the information provided by both entities to ensure that their female patients receive high-quality preventive care that will minimize their risk for CVD.

Nearly 3 out of 4 (71.9%) US women (and 72.6% of men) ages 60 to 79 years have cardiovascular disease (CVD)—the leading cause of death despite marked improvement in mortality rates in the last 4 decades. In that same age group, the prevalence of cerebral vascular disease is 8.2% in women and 7.2% in men.¹

The age-adjusted death rate for all adults is 135.1 in 100,000 for coronary heart disease (CHD) and 44.1 in 100,000 for cerebral vascular disease. In 2007, CVD caused 34.5% of deaths in women and 32.7% of deaths in men.¹

Evidence that CVD frequently manifests differently in women than in men led the American Heart Association (AHA) to issue recommendations for the prevention of CVD in women in 1999, and to follow with guidelines in 2004 and an update in 2007.^2-4 However, the recommended interventions were, with a few exceptions, the same as the recommendations for men. But that’s changed.

The latest update of the guidelines, published earlier this year, focuses more on sex-based differences, with the addition of pregnancy complications as a major risk factor, for example. (See “AHA’s 2011 CVD guideline update: What’s new?”.) Highlights of the guidelines,⁵ including the recommended interventions for all women (TABLE 1) and a comparison of its recommendations with those of the US Preventive Services Task Force (USPSTF)⁶ (TABLE 2)—are detailed here.

TABLE 1
AHA recommends these interventions for all women⁵

TABLE 2
CVD prevention in women: Comparing AHA¹and USPSTF recommendations^5,6

The AHA’s assessment of risk

The new guideline update recommends assessing each woman’s CVD risk and placing her into one of 3 risk groups—high risk, at risk, and ideal cardiovascular health (TABLE 3)—then using an algorithm to determine which preventive interventions to recommend based on her risk level.

This classification approach is challenging, for several reasons. It lumps women with markedly different risk profiles into the “at risk” group, a category that will likely apply to a high proportion of women. It also appears to encourage the use of diagnostic tests for subclinical vascular disease, for which there is no evidence of effectiveness. In addition, some of the terms used in the at-risk criteria, such as ”physical inactivity” and “poor diet,” are vague.

TABLE 3
Cardiovascular disease: How the AHA classifies women’s risk⁵

Some recommendations apply to all women, regardless of risk
The AHA recommendations for all women (TABLE 1) include smoking prevention or cessation, maintenance of optimal weight, regular physical activity, and a diet aimed at preventing CVD. The guidelines also emphasize that major CVD risks should be controlled, with either lifestyle and diet modifications (preferably) or pharmacotherapy. The aggressiveness of control targets depends on the level of risk and the presence of other risk factors.

The guidelines recommend against some interventions that are often used for CVD prevention, based on a high level of evidence that they are ineffective. These include estrogen or selective estrogen receptor modulators, antioxidant vitamins (vitamins E and C, and beta-carotene), folic acid with or without vitamins B6 and B12, and aspirin (for CHD prevention) for healthy women <65 years old.

The AHA does not take a position for or against several diagnostic and risk classification tools because of a lack of evidence of usefulness. These include CVD risk biomarkers such as high sensitivity C-reactive protein and imaging technologies such as coronary calcium scoring assessment.

AHA and USPSTF diverge, but not by much

Screening for conditions that increase CVD risk is not explicitly addressed in the AHA guidelines. Screening is implied by the proposed classification scheme, which includes the presence or absence of smoking, obesity, diabetes, hypertension, and dyslipidemia, but there is no guidance on when to start or stop screening for these conditions. The AHA and the USPSTF diverge on screening women for dyslipidemia, with the USPSTF recommending screening for lipid disorders only in women at increased risk for CHD.

The recommendations for optimal weight and activity levels in the AHA guidelines do not include advice on how to achieve them, nor do they call for an assessment of the effectiveness of behavioral counseling in the clinical setting. Because the USPSTF includes an assessment of, and recommendations for, asymptomatic patients in primary care settings, its recommendations do not address women with conditions such as established CVD, heart failure, or atrial fibrillation—which the AHA guidelines do.

Overall, the AHA and USPSTF agree more than they disagree, and each covers some areas that the other does not (TABLE 2). Family physicians can use the information provided by both entities to ensure that their female patients receive high-quality preventive care that will minimize their risk for CVD.

Evidence summary

NRT. A Cochrane review of 111 randomized controlled trials (RCTs) with a total of >40,000 subjects evaluated abstinence rates after 6 months of NRT and placebo or no treatment.¹ All forms of NRT increased abstinence vs placebo or no treatment, independent of setting, duration of treatment, and intensity of nonpharmacologic therapies. Overlapping confidence intervals suggested that no one form of NRT was superior. (The TABLE summarizes all the studies discussed here.)

Bupropion. A Cochrane review of 36 RCTs (N=11,140) showed higher abstinence rates with bupropion than placebo after ≥6 months of follow-up (average quit rate 17% vs 9%). Duration (6 vs 12 months) and intensity (150 vs 300 mg) of therapy didn’t influence the results.² Six separate RCTs comparing bupropion plus NRT with NRT alone showed significant heterogeneity, but found no significant differences using a mixed-effects model.²

Nortriptyline. A Cochrane review that pooled results from 6 RCTs (N=975) showed superior 6-month abstinence rates for nortriptyline compared with placebo.² Adding nicotine patches in other RCTs (N=1219) didn’t change abstinence rates.² No long-term studies have examined other tricyclic antidepressants.

Clonidine. A pooled analysis of 6 RCTs found clonidine superior to placebo after ≥12 weeks of follow-up.³ Results were heavily influenced by one trial limited to heavy smokers and poor tolerability due to adverse effects of therapy, especially sedation and dry mouth.

Nicotine receptor partial agonists and antagonists. Standard dose varenicline was more than twice as likely as placebo to produce abstinence at 6 months in a Cochrane review of 10 RCTs.⁴ Lower doses were slightly less effective, but had fewer side effects. Adverse effects included mild to moderate nausea and sleep disorders; causation has not been established between varenicline and rare postmarketing reports of severe psychiatric disturbances.^4,5

The pooled results of 3 RCTs suggested that varenicline was superior to bupropion, but different abstinence rates for bupropion users in other placebo-controlled trials necessitate caution in interpreting these results.⁴ Varenicline was not superior to NRT.⁴

One RCT (N=48) comparing nicotine patches plus the nicotine antagonist mecamylamine with patches plus placebo found improved abstinence rates at 6 and 12 months; a larger RCT didn’t support these findings.⁶

Table
How effective are smoking cessation interventions?

These interventions are not supported
A review of placebo-controlled RCTs found no evidence of improved abstinence at 6 to 12 months with fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, or monoamine oxidase inhibitors, alone or as adjuncts to NRT.²

No good evidence supports using anxiolytics, silver acetate, Nicobrevin (a nicotine-free smoking cessation aid), lobeline, or naltrexone for smoking cessation.^7-9

Simple advice and quit lines help
A Cochrane review of 17 RCTs found that simple advice improved quit rates and maintenance of abstinence at 12 months.^10-13

A review of 9 RCTs (N>24,000). found that telephone quit lines increased abstinence, particularly after more than 2 sessions.¹⁴

No high-quality studies demonstrate the effectiveness of acupuncture, hypnotherapy, or acupressure for smoking cessation.^15,16

Recommendations

The Agency for Health Care Research and Quality recommends counseling (including individual, group, and telephone sessions and brief physician advice) in addition to sustained-release bupropion, NRT, and varenicline as first-line agents. It considers clonidine and nortriptyline second-line therapies.¹⁷

Evidence summary

NRT. A Cochrane review of 111 randomized controlled trials (RCTs) with a total of >40,000 subjects evaluated abstinence rates after 6 months of NRT and placebo or no treatment.¹ All forms of NRT increased abstinence vs placebo or no treatment, independent of setting, duration of treatment, and intensity of nonpharmacologic therapies. Overlapping confidence intervals suggested that no one form of NRT was superior. (The TABLE summarizes all the studies discussed here.)

Bupropion. A Cochrane review of 36 RCTs (N=11,140) showed higher abstinence rates with bupropion than placebo after ≥6 months of follow-up (average quit rate 17% vs 9%). Duration (6 vs 12 months) and intensity (150 vs 300 mg) of therapy didn’t influence the results.² Six separate RCTs comparing bupropion plus NRT with NRT alone showed significant heterogeneity, but found no significant differences using a mixed-effects model.²

Nortriptyline. A Cochrane review that pooled results from 6 RCTs (N=975) showed superior 6-month abstinence rates for nortriptyline compared with placebo.² Adding nicotine patches in other RCTs (N=1219) didn’t change abstinence rates.² No long-term studies have examined other tricyclic antidepressants.

Clonidine. A pooled analysis of 6 RCTs found clonidine superior to placebo after ≥12 weeks of follow-up.³ Results were heavily influenced by one trial limited to heavy smokers and poor tolerability due to adverse effects of therapy, especially sedation and dry mouth.

Nicotine receptor partial agonists and antagonists. Standard dose varenicline was more than twice as likely as placebo to produce abstinence at 6 months in a Cochrane review of 10 RCTs.⁴ Lower doses were slightly less effective, but had fewer side effects. Adverse effects included mild to moderate nausea and sleep disorders; causation has not been established between varenicline and rare postmarketing reports of severe psychiatric disturbances.^4,5

The pooled results of 3 RCTs suggested that varenicline was superior to bupropion, but different abstinence rates for bupropion users in other placebo-controlled trials necessitate caution in interpreting these results.⁴ Varenicline was not superior to NRT.⁴

One RCT (N=48) comparing nicotine patches plus the nicotine antagonist mecamylamine with patches plus placebo found improved abstinence rates at 6 and 12 months; a larger RCT didn’t support these findings.⁶

Table
How effective are smoking cessation interventions?

These interventions are not supported
A review of placebo-controlled RCTs found no evidence of improved abstinence at 6 to 12 months with fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, or monoamine oxidase inhibitors, alone or as adjuncts to NRT.²

No good evidence supports using anxiolytics, silver acetate, Nicobrevin (a nicotine-free smoking cessation aid), lobeline, or naltrexone for smoking cessation.^7-9

Simple advice and quit lines help
A Cochrane review of 17 RCTs found that simple advice improved quit rates and maintenance of abstinence at 12 months.^10-13

A review of 9 RCTs (N>24,000). found that telephone quit lines increased abstinence, particularly after more than 2 sessions.¹⁴

No high-quality studies demonstrate the effectiveness of acupuncture, hypnotherapy, or acupressure for smoking cessation.^15,16

Recommendations

The Agency for Health Care Research and Quality recommends counseling (including individual, group, and telephone sessions and brief physician advice) in addition to sustained-release bupropion, NRT, and varenicline as first-line agents. It considers clonidine and nortriptyline second-line therapies.¹⁷

Evidence summary

NRT. A Cochrane review of 111 randomized controlled trials (RCTs) with a total of >40,000 subjects evaluated abstinence rates after 6 months of NRT and placebo or no treatment.¹ All forms of NRT increased abstinence vs placebo or no treatment, independent of setting, duration of treatment, and intensity of nonpharmacologic therapies. Overlapping confidence intervals suggested that no one form of NRT was superior. (The TABLE summarizes all the studies discussed here.)

Bupropion. A Cochrane review of 36 RCTs (N=11,140) showed higher abstinence rates with bupropion than placebo after ≥6 months of follow-up (average quit rate 17% vs 9%). Duration (6 vs 12 months) and intensity (150 vs 300 mg) of therapy didn’t influence the results.² Six separate RCTs comparing bupropion plus NRT with NRT alone showed significant heterogeneity, but found no significant differences using a mixed-effects model.²

Nortriptyline. A Cochrane review that pooled results from 6 RCTs (N=975) showed superior 6-month abstinence rates for nortriptyline compared with placebo.² Adding nicotine patches in other RCTs (N=1219) didn’t change abstinence rates.² No long-term studies have examined other tricyclic antidepressants.

Clonidine. A pooled analysis of 6 RCTs found clonidine superior to placebo after ≥12 weeks of follow-up.³ Results were heavily influenced by one trial limited to heavy smokers and poor tolerability due to adverse effects of therapy, especially sedation and dry mouth.

Nicotine receptor partial agonists and antagonists. Standard dose varenicline was more than twice as likely as placebo to produce abstinence at 6 months in a Cochrane review of 10 RCTs.⁴ Lower doses were slightly less effective, but had fewer side effects. Adverse effects included mild to moderate nausea and sleep disorders; causation has not been established between varenicline and rare postmarketing reports of severe psychiatric disturbances.^4,5

The pooled results of 3 RCTs suggested that varenicline was superior to bupropion, but different abstinence rates for bupropion users in other placebo-controlled trials necessitate caution in interpreting these results.⁴ Varenicline was not superior to NRT.⁴

One RCT (N=48) comparing nicotine patches plus the nicotine antagonist mecamylamine with patches plus placebo found improved abstinence rates at 6 and 12 months; a larger RCT didn’t support these findings.⁶

Table
How effective are smoking cessation interventions?

These interventions are not supported
A review of placebo-controlled RCTs found no evidence of improved abstinence at 6 to 12 months with fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, or monoamine oxidase inhibitors, alone or as adjuncts to NRT.²

No good evidence supports using anxiolytics, silver acetate, Nicobrevin (a nicotine-free smoking cessation aid), lobeline, or naltrexone for smoking cessation.^7-9

Simple advice and quit lines help
A Cochrane review of 17 RCTs found that simple advice improved quit rates and maintenance of abstinence at 12 months.^10-13

A review of 9 RCTs (N>24,000). found that telephone quit lines increased abstinence, particularly after more than 2 sessions.¹⁴

No high-quality studies demonstrate the effectiveness of acupuncture, hypnotherapy, or acupressure for smoking cessation.^15,16

Recommendations

The Agency for Health Care Research and Quality recommends counseling (including individual, group, and telephone sessions and brief physician advice) in addition to sustained-release bupropion, NRT, and varenicline as first-line agents. It considers clonidine and nortriptyline second-line therapies.¹⁷

This article is an expansion of a poster session presented at the 12th annual Northeastern Ohio Universities College of Medicine Department of Surgery Resident Research Day in May 2009 and at the American College of Preventive Medicine Annual Meeting in February 2010.

The release of the Wii—Nintendo’s 4th generation gaming console—in 2006 revolutionized the video game industry. By March 31, 2010, more than 70 million units had been sold worldwide, earning Wii the title of “fastest-selling game console of all time.”^1-3

Today, there are several game consoles that, like Wii, allow the user not only to push buttons or move levers, but to control the game using physical movements (TABLE 1). And the devices and the many sports they simulate—once popular primarily among adolescents—are in widespread use by people of all ages, including the young and fit, out-of-shape “arm chair” athletes, and elderly people in senior housing, rehabilitation centers, and long-term care facilities alike.⁴

Not surprisingly, simulated sports play has spawned an array of repetitive motion and overuse injuries. To identify and treat them, ask all patients who present with musculoskeletal injuries whether they engage in game console sports activities; if so, identify the type of game and how much time they spend playing it each day. Although injuries associated with specific video games are often given names like “Wii-itis,”⁵ “Nintendinitis,”⁶ and “Playstation thumb,”⁷ the types of injuries caused by playing simulated sports are generally the same as (or similar to) injuries sustained by those engaging in the sport itself.

TABLE 1
Popular motion-controlled games: A partial list

Video game pathology is well established

In 1987, Osterman et al published the first report of a musculoskeletal disorder associated with electronic games—a case of volar flexor tenosynovitis (“joystick digit”) trigger finger.⁸ Several years later, a physician coined the term “Nintendinitis” to describe video game-related overuse syndrome⁶—acute tendinopathy of the extensor pollicis longus tendon after prolonged play with early versions of the thumb-activated game controller.^9,10 In 2002, a child using a vibrating Sony Playstation for up to 7 hours a day received a diagnosis of vibratory syndrome of the hand.¹¹ A few years later, a report of “Playstation thumb,” an overuse syndrome associated with later generations of game consoles, followed.⁷

Several other reports of game-related injury patterns can be found in medical journals, including pressure ulcer formation (“ulcerative Nintendinitis”),¹² the “How!” sign of central palmar blistering,¹³ “mouse elbow” secondary to epicondylitis,¹⁴ and other tendinopathies associated with various gaming consoles.^10,15,16 All the reports clearly describe the relationship between video game use and the pathology, and clinical improvement after cessation of the activity.

Many manifestations of Wii-itis
An epidemiologic review of the National Electronic Injury Surveillance System (http://www.cpsc.gov/library/neiss.html) found that in the Wii’s first year, 67% of the musculoskeletal injuries reported (29% were defined as sprains and strains and 38% as overuse injuries) involved the use of the Wii to play simulated sports.¹⁷ Overuse syndrome associated with Wii was initially called “acute Wii-itis,”⁵ a description of acute tendinopathy of the infraspinatus.¹⁸ (Infraspinatus tendinopathy is most commonly associated with games involving intense arm activity, including Wii baseball, bowling, and boxing (TABLE 2).⁵ However, Wii-itis is now widely used to describe any acute inflammatory syndrome associated with use of this popular game console.

Wii knee, for example, refers to an acute patellar dislocation associated with simulated bowling.¹⁹ Multiple cases of patellar injury, including associated osteochondral fracture, have been reported in association with a variety of game titles, including Raymond Raving Rabbids and Brunswick Pro Bowling.¹⁹ In a review of self-reported Wii injuries, patellar dislocation was the fourth most common injury (hand lacerations were first, followed by periorbital hematoma [“black eye”], and forehead lacerations/ecchymoses).²⁰

Wii shoulder, another variant of Wii-itis, is an acute inflammation of the upper extremity musculature after repetitive motion. This injury is most often associated with games that require swinging of the controller, such as Wii tennis or bowling. Upper extremity magnetic resonance imaging (MRI) of one Wii enthusiast revealed inflammatory swelling of the shoulder joint that extended to the suprascapular region, corresponding to a diagnosis of delayed–onset muscle soreness (DOMS).⁹

DOMS, which is often associated with acute injury patterns, is a well-accepted diagnosis among patients who play physically interactive sports and, by extension, video games.¹⁷ Usually lacking frank deformity on plain radiographs, DOMS is a disorder of the soft tissue that can best be visualized with MRI delineation of tissue planes and musculature compartments. Clinical signs and symptoms of DOMS can include edema of the affected extremity, rubor, and tenderness to palpation during active range of motion. Treatment for DOMS, like all RMIs, includes cessation of the offending activity.

Another recently reported variant of Wii-itis is the acute onset of carpal tunnel syndrome²¹ after playing Wii bowling for long periods of time. The case involved a 19-year-old woman who presented with swelling over the volar wrist and had positive Tinel and Phalen signs. She received conservative treatment with etodolac, a nightly volar splint, cold compresses, and rest.

Achilles Wii-itis refers to a partial or complete rupture of the Achilles tendon during simulated sports activity.²² This injury has been reported in people using the Wii Fit exercise pad for virtual running and stretching, and is diagnosed clinically with a positive Thompson sign (failure to plantar flex the foot while compressing the gastrocnemius). Complete Achilles rupture requires surgical repair, but less severe cases can be treated conservatively, with cold compresses, lifestyle modification, and nonsteroidal anti-inflammatory drugs (NSAIDs).

TABLE 2
Repetitive motion injuries (and possible causes)*^30,36

Categorizing Wii-type injuries

Game-related injuries typically fall into 4 broad categories: tendinopathy, bursitis, enthesitis, and epicondylitis. (See TABLE 2 for a list of games with the potential to cause particular types of injuries.)

Tendinopathy. Overuse tendon injuries, or tendinopathies, account for up to 50% of all sports-related injuries.²³ By extrapolation, physically interactive game systems that simulate actual sports can be expected to increase tendon overuse injuries.

Most major tendons are vulnerable to overuse injury, including the Achilles (FIGURE), as noted earlier; and the patellar, rotator cuff, and forearm extensor tendons, among others. Repetitive motion, or strain, injuries to these tendons are often thought to be cumulative, with hypoperfusion, local inflammation, and neuropathy contributing to the degree of tendinopathy. Other risk factors for tendon injury include age and sex (men have a higher relative risk than women; older people, in their fourth and fifth decades of life, also face an increased risk), postmenopausal status, obesity, use of fluoroquinolone antibiotics or corticosteroids, and playing on nonpadded surfaces.^24-29

Conservative therapy, with cessation of the offending activity and rest of the affected extremity, is the initial treatment of choice for tendinopathy. Severe cases of compound injuries or tendon reinjury can also be treated with splinting, taping, cryotherapy, electrotherapy, deep tissue tendon massage, pharmaceuticals (NSAIDs and corticosteroid injections), and early rehabilitation.^15,30 Surgery may eventually be required to remove fibrotic tissue, modify the vascularity, or reconstruct the tendon.¹⁵

Bursitis. Bursitis is characterized by inflammation of the subacromial, olecranon, trochanteric, prepatellar, suprapatellar, infrapatellar, pes anserine, or iliotibial bursa—synovial-lined cavities overlying bony prominences that minimize the friction of movement.³¹ Patellar and olecranon bursitis are most frequently associated with sports, particularly soccer and golf.

Clinically characterized by pain on flexion, bursitis can also present with localized tenderness, stiffness, and swelling of the affected joint. Bursitis generally responds to RICE (rest, ice, compression, elevation) therapy, but can potentially advance to a chronic disease state if the activity that caused the inflammation continues.³¹

Enthesitis. Characterized by inflammation of the bony insertions of a tendon or ligament, enthesitis is generally linked to an autoimmune disease such as ankylosing spondylitis or rheumatoid arthritis. But it can also be an acquired condition associated with repetitive motion. Sports-related activity is the most common cause of acquired enthesitis,³² with injury most likely to occur at the Achilles tendon, the insertion point of the tibial tuberosity, or the iliac crest.³³ Like most RMIs, acquired enthesitis can usually be treated simply by stopping the offending activity. If not properly recognized or treated, however, permanent injury can occur. ³⁴

Epicondylitis. This RMI results in pain or ipsilateral weakness of the upper extremity due to repetitive strain at the musculotendinous junction and its origin at the epicondyle. Neuropraxia is often associated with epicondylitis due to posterior interosseous nerve, median nerve, or ulnar nerve involvement at either the medial or lateral epicondyles.³⁵

Commonly affecting computer users who perform repetitive motion via mouse manipulation, the term “mouse elbow” was first described in 1992.¹⁴ Golfer’s elbow (with involvement of the medial epicondyle), and tennis elbow (involving the lateral epicondyle) are also common, and individuals who frequently play simulated golf or tennis games are at risk.

FIGURE
Achilles tendon injury

Tell patients how to prevent injury

Older patients and deconditioned “arm chair” athletes who are unaccustomed to prolonged physical activity face an increased risk for injuries related to video game sports. You can help by pointing out that because simulated activities require a fraction of the strength and endurance required to play the actual sport, people who might normally tire easily are apt to overdo it.

In fact, Nintendo has a dedicated safety page regarding the use of game consoles on its Web site (http://www.nintendo.com/consumer/wiisafety.jsp). The company advises Wii users to take a 10- to 15-minute break every hour, even if they don’t think they need it, to prevent repetitive motion and eyestrain injuries, and to stop playing for several hours if they experience tingling, numbness, burning, or stiffness. Some software titles, including Wii Fit, are programmed to remind users to take a break after they’ve been playing nonstop for 45 minutes to an hour. You can help by reminding patients of all ages that warm-up exercises, moderation, and hydration are crucial, whether the sports they’re engaging in are virtual or real.

Acknowledgement

The authors would like to thank Dan Dunlany for his invaluable research assistance.

CORRESPONDENCE
Lisa M. Coughlin, MD, Department of Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614; [email protected]

This article is an expansion of a poster session presented at the 12th annual Northeastern Ohio Universities College of Medicine Department of Surgery Resident Research Day in May 2009 and at the American College of Preventive Medicine Annual Meeting in February 2010.

The release of the Wii—Nintendo’s 4th generation gaming console—in 2006 revolutionized the video game industry. By March 31, 2010, more than 70 million units had been sold worldwide, earning Wii the title of “fastest-selling game console of all time.”^1-3

Today, there are several game consoles that, like Wii, allow the user not only to push buttons or move levers, but to control the game using physical movements (TABLE 1). And the devices and the many sports they simulate—once popular primarily among adolescents—are in widespread use by people of all ages, including the young and fit, out-of-shape “arm chair” athletes, and elderly people in senior housing, rehabilitation centers, and long-term care facilities alike.⁴

Not surprisingly, simulated sports play has spawned an array of repetitive motion and overuse injuries. To identify and treat them, ask all patients who present with musculoskeletal injuries whether they engage in game console sports activities; if so, identify the type of game and how much time they spend playing it each day. Although injuries associated with specific video games are often given names like “Wii-itis,”⁵ “Nintendinitis,”⁶ and “Playstation thumb,”⁷ the types of injuries caused by playing simulated sports are generally the same as (or similar to) injuries sustained by those engaging in the sport itself.

TABLE 1
Popular motion-controlled games: A partial list

Video game pathology is well established

In 1987, Osterman et al published the first report of a musculoskeletal disorder associated with electronic games—a case of volar flexor tenosynovitis (“joystick digit”) trigger finger.⁸ Several years later, a physician coined the term “Nintendinitis” to describe video game-related overuse syndrome⁶—acute tendinopathy of the extensor pollicis longus tendon after prolonged play with early versions of the thumb-activated game controller.^9,10 In 2002, a child using a vibrating Sony Playstation for up to 7 hours a day received a diagnosis of vibratory syndrome of the hand.¹¹ A few years later, a report of “Playstation thumb,” an overuse syndrome associated with later generations of game consoles, followed.⁷

Several other reports of game-related injury patterns can be found in medical journals, including pressure ulcer formation (“ulcerative Nintendinitis”),¹² the “How!” sign of central palmar blistering,¹³ “mouse elbow” secondary to epicondylitis,¹⁴ and other tendinopathies associated with various gaming consoles.^10,15,16 All the reports clearly describe the relationship between video game use and the pathology, and clinical improvement after cessation of the activity.

Many manifestations of Wii-itis
An epidemiologic review of the National Electronic Injury Surveillance System (http://www.cpsc.gov/library/neiss.html) found that in the Wii’s first year, 67% of the musculoskeletal injuries reported (29% were defined as sprains and strains and 38% as overuse injuries) involved the use of the Wii to play simulated sports.¹⁷ Overuse syndrome associated with Wii was initially called “acute Wii-itis,”⁵ a description of acute tendinopathy of the infraspinatus.¹⁸ (Infraspinatus tendinopathy is most commonly associated with games involving intense arm activity, including Wii baseball, bowling, and boxing (TABLE 2).⁵ However, Wii-itis is now widely used to describe any acute inflammatory syndrome associated with use of this popular game console.

Wii knee, for example, refers to an acute patellar dislocation associated with simulated bowling.¹⁹ Multiple cases of patellar injury, including associated osteochondral fracture, have been reported in association with a variety of game titles, including Raymond Raving Rabbids and Brunswick Pro Bowling.¹⁹ In a review of self-reported Wii injuries, patellar dislocation was the fourth most common injury (hand lacerations were first, followed by periorbital hematoma [“black eye”], and forehead lacerations/ecchymoses).²⁰

Wii shoulder, another variant of Wii-itis, is an acute inflammation of the upper extremity musculature after repetitive motion. This injury is most often associated with games that require swinging of the controller, such as Wii tennis or bowling. Upper extremity magnetic resonance imaging (MRI) of one Wii enthusiast revealed inflammatory swelling of the shoulder joint that extended to the suprascapular region, corresponding to a diagnosis of delayed–onset muscle soreness (DOMS).⁹

DOMS, which is often associated with acute injury patterns, is a well-accepted diagnosis among patients who play physically interactive sports and, by extension, video games.¹⁷ Usually lacking frank deformity on plain radiographs, DOMS is a disorder of the soft tissue that can best be visualized with MRI delineation of tissue planes and musculature compartments. Clinical signs and symptoms of DOMS can include edema of the affected extremity, rubor, and tenderness to palpation during active range of motion. Treatment for DOMS, like all RMIs, includes cessation of the offending activity.

Another recently reported variant of Wii-itis is the acute onset of carpal tunnel syndrome²¹ after playing Wii bowling for long periods of time. The case involved a 19-year-old woman who presented with swelling over the volar wrist and had positive Tinel and Phalen signs. She received conservative treatment with etodolac, a nightly volar splint, cold compresses, and rest.

Achilles Wii-itis refers to a partial or complete rupture of the Achilles tendon during simulated sports activity.²² This injury has been reported in people using the Wii Fit exercise pad for virtual running and stretching, and is diagnosed clinically with a positive Thompson sign (failure to plantar flex the foot while compressing the gastrocnemius). Complete Achilles rupture requires surgical repair, but less severe cases can be treated conservatively, with cold compresses, lifestyle modification, and nonsteroidal anti-inflammatory drugs (NSAIDs).

TABLE 2
Repetitive motion injuries (and possible causes)*^30,36

Categorizing Wii-type injuries

Game-related injuries typically fall into 4 broad categories: tendinopathy, bursitis, enthesitis, and epicondylitis. (See TABLE 2 for a list of games with the potential to cause particular types of injuries.)

Tendinopathy. Overuse tendon injuries, or tendinopathies, account for up to 50% of all sports-related injuries.²³ By extrapolation, physically interactive game systems that simulate actual sports can be expected to increase tendon overuse injuries.

Most major tendons are vulnerable to overuse injury, including the Achilles (FIGURE), as noted earlier; and the patellar, rotator cuff, and forearm extensor tendons, among others. Repetitive motion, or strain, injuries to these tendons are often thought to be cumulative, with hypoperfusion, local inflammation, and neuropathy contributing to the degree of tendinopathy. Other risk factors for tendon injury include age and sex (men have a higher relative risk than women; older people, in their fourth and fifth decades of life, also face an increased risk), postmenopausal status, obesity, use of fluoroquinolone antibiotics or corticosteroids, and playing on nonpadded surfaces.^24-29

Conservative therapy, with cessation of the offending activity and rest of the affected extremity, is the initial treatment of choice for tendinopathy. Severe cases of compound injuries or tendon reinjury can also be treated with splinting, taping, cryotherapy, electrotherapy, deep tissue tendon massage, pharmaceuticals (NSAIDs and corticosteroid injections), and early rehabilitation.^15,30 Surgery may eventually be required to remove fibrotic tissue, modify the vascularity, or reconstruct the tendon.¹⁵

Bursitis. Bursitis is characterized by inflammation of the subacromial, olecranon, trochanteric, prepatellar, suprapatellar, infrapatellar, pes anserine, or iliotibial bursa—synovial-lined cavities overlying bony prominences that minimize the friction of movement.³¹ Patellar and olecranon bursitis are most frequently associated with sports, particularly soccer and golf.

Clinically characterized by pain on flexion, bursitis can also present with localized tenderness, stiffness, and swelling of the affected joint. Bursitis generally responds to RICE (rest, ice, compression, elevation) therapy, but can potentially advance to a chronic disease state if the activity that caused the inflammation continues.³¹

Enthesitis. Characterized by inflammation of the bony insertions of a tendon or ligament, enthesitis is generally linked to an autoimmune disease such as ankylosing spondylitis or rheumatoid arthritis. But it can also be an acquired condition associated with repetitive motion. Sports-related activity is the most common cause of acquired enthesitis,³² with injury most likely to occur at the Achilles tendon, the insertion point of the tibial tuberosity, or the iliac crest.³³ Like most RMIs, acquired enthesitis can usually be treated simply by stopping the offending activity. If not properly recognized or treated, however, permanent injury can occur. ³⁴

Epicondylitis. This RMI results in pain or ipsilateral weakness of the upper extremity due to repetitive strain at the musculotendinous junction and its origin at the epicondyle. Neuropraxia is often associated with epicondylitis due to posterior interosseous nerve, median nerve, or ulnar nerve involvement at either the medial or lateral epicondyles.³⁵

Commonly affecting computer users who perform repetitive motion via mouse manipulation, the term “mouse elbow” was first described in 1992.¹⁴ Golfer’s elbow (with involvement of the medial epicondyle), and tennis elbow (involving the lateral epicondyle) are also common, and individuals who frequently play simulated golf or tennis games are at risk.

FIGURE
Achilles tendon injury

Tell patients how to prevent injury

Older patients and deconditioned “arm chair” athletes who are unaccustomed to prolonged physical activity face an increased risk for injuries related to video game sports. You can help by pointing out that because simulated activities require a fraction of the strength and endurance required to play the actual sport, people who might normally tire easily are apt to overdo it.

In fact, Nintendo has a dedicated safety page regarding the use of game consoles on its Web site (http://www.nintendo.com/consumer/wiisafety.jsp). The company advises Wii users to take a 10- to 15-minute break every hour, even if they don’t think they need it, to prevent repetitive motion and eyestrain injuries, and to stop playing for several hours if they experience tingling, numbness, burning, or stiffness. Some software titles, including Wii Fit, are programmed to remind users to take a break after they’ve been playing nonstop for 45 minutes to an hour. You can help by reminding patients of all ages that warm-up exercises, moderation, and hydration are crucial, whether the sports they’re engaging in are virtual or real.

Acknowledgement

The authors would like to thank Dan Dunlany for his invaluable research assistance.

CORRESPONDENCE
Lisa M. Coughlin, MD, Department of Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614; [email protected]

This article is an expansion of a poster session presented at the 12th annual Northeastern Ohio Universities College of Medicine Department of Surgery Resident Research Day in May 2009 and at the American College of Preventive Medicine Annual Meeting in February 2010.

The release of the Wii—Nintendo’s 4th generation gaming console—in 2006 revolutionized the video game industry. By March 31, 2010, more than 70 million units had been sold worldwide, earning Wii the title of “fastest-selling game console of all time.”^1-3

Today, there are several game consoles that, like Wii, allow the user not only to push buttons or move levers, but to control the game using physical movements (TABLE 1). And the devices and the many sports they simulate—once popular primarily among adolescents—are in widespread use by people of all ages, including the young and fit, out-of-shape “arm chair” athletes, and elderly people in senior housing, rehabilitation centers, and long-term care facilities alike.⁴

Not surprisingly, simulated sports play has spawned an array of repetitive motion and overuse injuries. To identify and treat them, ask all patients who present with musculoskeletal injuries whether they engage in game console sports activities; if so, identify the type of game and how much time they spend playing it each day. Although injuries associated with specific video games are often given names like “Wii-itis,”⁵ “Nintendinitis,”⁶ and “Playstation thumb,”⁷ the types of injuries caused by playing simulated sports are generally the same as (or similar to) injuries sustained by those engaging in the sport itself.

TABLE 1
Popular motion-controlled games: A partial list

Video game pathology is well established

In 1987, Osterman et al published the first report of a musculoskeletal disorder associated with electronic games—a case of volar flexor tenosynovitis (“joystick digit”) trigger finger.⁸ Several years later, a physician coined the term “Nintendinitis” to describe video game-related overuse syndrome⁶—acute tendinopathy of the extensor pollicis longus tendon after prolonged play with early versions of the thumb-activated game controller.^9,10 In 2002, a child using a vibrating Sony Playstation for up to 7 hours a day received a diagnosis of vibratory syndrome of the hand.¹¹ A few years later, a report of “Playstation thumb,” an overuse syndrome associated with later generations of game consoles, followed.⁷

Several other reports of game-related injury patterns can be found in medical journals, including pressure ulcer formation (“ulcerative Nintendinitis”),¹² the “How!” sign of central palmar blistering,¹³ “mouse elbow” secondary to epicondylitis,¹⁴ and other tendinopathies associated with various gaming consoles.^10,15,16 All the reports clearly describe the relationship between video game use and the pathology, and clinical improvement after cessation of the activity.

Many manifestations of Wii-itis
An epidemiologic review of the National Electronic Injury Surveillance System (http://www.cpsc.gov/library/neiss.html) found that in the Wii’s first year, 67% of the musculoskeletal injuries reported (29% were defined as sprains and strains and 38% as overuse injuries) involved the use of the Wii to play simulated sports.¹⁷ Overuse syndrome associated with Wii was initially called “acute Wii-itis,”⁵ a description of acute tendinopathy of the infraspinatus.¹⁸ (Infraspinatus tendinopathy is most commonly associated with games involving intense arm activity, including Wii baseball, bowling, and boxing (TABLE 2).⁵ However, Wii-itis is now widely used to describe any acute inflammatory syndrome associated with use of this popular game console.

Wii knee, for example, refers to an acute patellar dislocation associated with simulated bowling.¹⁹ Multiple cases of patellar injury, including associated osteochondral fracture, have been reported in association with a variety of game titles, including Raymond Raving Rabbids and Brunswick Pro Bowling.¹⁹ In a review of self-reported Wii injuries, patellar dislocation was the fourth most common injury (hand lacerations were first, followed by periorbital hematoma [“black eye”], and forehead lacerations/ecchymoses).²⁰

Wii shoulder, another variant of Wii-itis, is an acute inflammation of the upper extremity musculature after repetitive motion. This injury is most often associated with games that require swinging of the controller, such as Wii tennis or bowling. Upper extremity magnetic resonance imaging (MRI) of one Wii enthusiast revealed inflammatory swelling of the shoulder joint that extended to the suprascapular region, corresponding to a diagnosis of delayed–onset muscle soreness (DOMS).⁹

DOMS, which is often associated with acute injury patterns, is a well-accepted diagnosis among patients who play physically interactive sports and, by extension, video games.¹⁷ Usually lacking frank deformity on plain radiographs, DOMS is a disorder of the soft tissue that can best be visualized with MRI delineation of tissue planes and musculature compartments. Clinical signs and symptoms of DOMS can include edema of the affected extremity, rubor, and tenderness to palpation during active range of motion. Treatment for DOMS, like all RMIs, includes cessation of the offending activity.

Another recently reported variant of Wii-itis is the acute onset of carpal tunnel syndrome²¹ after playing Wii bowling for long periods of time. The case involved a 19-year-old woman who presented with swelling over the volar wrist and had positive Tinel and Phalen signs. She received conservative treatment with etodolac, a nightly volar splint, cold compresses, and rest.

Achilles Wii-itis refers to a partial or complete rupture of the Achilles tendon during simulated sports activity.²² This injury has been reported in people using the Wii Fit exercise pad for virtual running and stretching, and is diagnosed clinically with a positive Thompson sign (failure to plantar flex the foot while compressing the gastrocnemius). Complete Achilles rupture requires surgical repair, but less severe cases can be treated conservatively, with cold compresses, lifestyle modification, and nonsteroidal anti-inflammatory drugs (NSAIDs).

TABLE 2
Repetitive motion injuries (and possible causes)*^30,36

Categorizing Wii-type injuries

Game-related injuries typically fall into 4 broad categories: tendinopathy, bursitis, enthesitis, and epicondylitis. (See TABLE 2 for a list of games with the potential to cause particular types of injuries.)

Tendinopathy. Overuse tendon injuries, or tendinopathies, account for up to 50% of all sports-related injuries.²³ By extrapolation, physically interactive game systems that simulate actual sports can be expected to increase tendon overuse injuries.

Most major tendons are vulnerable to overuse injury, including the Achilles (FIGURE), as noted earlier; and the patellar, rotator cuff, and forearm extensor tendons, among others. Repetitive motion, or strain, injuries to these tendons are often thought to be cumulative, with hypoperfusion, local inflammation, and neuropathy contributing to the degree of tendinopathy. Other risk factors for tendon injury include age and sex (men have a higher relative risk than women; older people, in their fourth and fifth decades of life, also face an increased risk), postmenopausal status, obesity, use of fluoroquinolone antibiotics or corticosteroids, and playing on nonpadded surfaces.^24-29

Conservative therapy, with cessation of the offending activity and rest of the affected extremity, is the initial treatment of choice for tendinopathy. Severe cases of compound injuries or tendon reinjury can also be treated with splinting, taping, cryotherapy, electrotherapy, deep tissue tendon massage, pharmaceuticals (NSAIDs and corticosteroid injections), and early rehabilitation.^15,30 Surgery may eventually be required to remove fibrotic tissue, modify the vascularity, or reconstruct the tendon.¹⁵

Bursitis. Bursitis is characterized by inflammation of the subacromial, olecranon, trochanteric, prepatellar, suprapatellar, infrapatellar, pes anserine, or iliotibial bursa—synovial-lined cavities overlying bony prominences that minimize the friction of movement.³¹ Patellar and olecranon bursitis are most frequently associated with sports, particularly soccer and golf.

Clinically characterized by pain on flexion, bursitis can also present with localized tenderness, stiffness, and swelling of the affected joint. Bursitis generally responds to RICE (rest, ice, compression, elevation) therapy, but can potentially advance to a chronic disease state if the activity that caused the inflammation continues.³¹

Enthesitis. Characterized by inflammation of the bony insertions of a tendon or ligament, enthesitis is generally linked to an autoimmune disease such as ankylosing spondylitis or rheumatoid arthritis. But it can also be an acquired condition associated with repetitive motion. Sports-related activity is the most common cause of acquired enthesitis,³² with injury most likely to occur at the Achilles tendon, the insertion point of the tibial tuberosity, or the iliac crest.³³ Like most RMIs, acquired enthesitis can usually be treated simply by stopping the offending activity. If not properly recognized or treated, however, permanent injury can occur. ³⁴

Epicondylitis. This RMI results in pain or ipsilateral weakness of the upper extremity due to repetitive strain at the musculotendinous junction and its origin at the epicondyle. Neuropraxia is often associated with epicondylitis due to posterior interosseous nerve, median nerve, or ulnar nerve involvement at either the medial or lateral epicondyles.³⁵

Commonly affecting computer users who perform repetitive motion via mouse manipulation, the term “mouse elbow” was first described in 1992.¹⁴ Golfer’s elbow (with involvement of the medial epicondyle), and tennis elbow (involving the lateral epicondyle) are also common, and individuals who frequently play simulated golf or tennis games are at risk.

FIGURE
Achilles tendon injury

Tell patients how to prevent injury

Older patients and deconditioned “arm chair” athletes who are unaccustomed to prolonged physical activity face an increased risk for injuries related to video game sports. You can help by pointing out that because simulated activities require a fraction of the strength and endurance required to play the actual sport, people who might normally tire easily are apt to overdo it.

In fact, Nintendo has a dedicated safety page regarding the use of game consoles on its Web site (http://www.nintendo.com/consumer/wiisafety.jsp). The company advises Wii users to take a 10- to 15-minute break every hour, even if they don’t think they need it, to prevent repetitive motion and eyestrain injuries, and to stop playing for several hours if they experience tingling, numbness, burning, or stiffness. Some software titles, including Wii Fit, are programmed to remind users to take a break after they’ve been playing nonstop for 45 minutes to an hour. You can help by reminding patients of all ages that warm-up exercises, moderation, and hydration are crucial, whether the sports they’re engaging in are virtual or real.

Acknowledgement

The authors would like to thank Dan Dunlany for his invaluable research assistance.

CORRESPONDENCE
Lisa M. Coughlin, MD, Department of Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614; [email protected]

CASE: Pain during intercourse, well after mesh implantation

Your patient, 61 years old, para 3, has come to your office by referral with a complaint of dyspareunia. The history includes placement of a synthetic vaginal mesh kit 14 months earlier for prolapse.

The medical record shows that the referring physician performed a “mesh excision” 1 year after the original procedure.

The woman reports that she is “very frustrated” that she is still dealing with this problem so long after the original procedure.

On examination, you note a 2.5-cm diameter area of exposed mesh in the anterior vagina, with healthy surrounding tissue and without inflammation or purulence (FIGURE 1). You are unable to reproduce her complaint of pain on vaginal examination.

What options can you offer to this woman? And will those options meet her therapeutic expectations?

FIGURE 1 Examination of your referred patient: Mesh is noticeably exposedThe recent increase in the use of mesh grafts to reconstruct pelvic anatomy has been directed mainly at improving surgical outcomes. Yet, at the same time, gynecologic surgeons find themselves facing a rise in associated complications of such surgery that they did not see previously.

Among the most troublesome and concerning of those complications are 1) exposure of mesh through the vaginal epithelium and 2) contraction or hardening of mesh (or both) that can result in dyspareunia and chronic pelvic pain. Other, rare complications include infection and fistula.

Our goal in this article is to address the management of graft-healing abnormalities in which a segment of the mesh is palpable or visible, or both, within the vaginal canal. Our focus is on simple abnormalities that can be managed by most generalist gynecologists; to be clear, more complex abnormalities, and those that provoke more serious or lasting symptoms, belong under the care of a specialist.

A recent shift in terminology is significant

Early on, this complication was called “erosion” as understanding of the mechanism of its development grew, however, terminology applied to the problem has changed.

In fact, mesh itself very rarely erodes into the vagina or an underlying viscus. Instead, the complication occurs most commonly as a result of disruption of a suture line—most likely the result of a hematoma or localized inflammation that develops postoperatively.

“Exposure” (our preference here) and “extrusion” are now the recommended terms, based on a consensus terminology document published this year jointly by the International Urogynecological Association and the International Continence Society.¹

Exposure of implanted mesh is considered a “simple” healing abnormality because it typically

• occurs along the suture line and early in the course of healing
• is not associated with infection of the graft.²

The typical physical appearance is one of visible mesh along an open suture line without granulation tissue or purulence—again, see FIGURE 1. The mesh is firmly adherent to the vaginal epithelial edges and underlying fascia.

The reported incidence of mesh exposures—in regard to currently used meshes, which are all Type-1, monofilament, macroporous polypropylene grafts—is approximately 10% but as high as 15% to 20% in some reported series.^3,4 The higher rates of exposure are usually seen in series in which some patients have had a synthetic graft implanted as an overlay to fascial midline plication. When the graft is implanted in the subfascial layer of the vaginal wall (i.e., without midline plication), however, the reported rate of exposure falls—to 5% to 10%.^5-7

Recommendations for management

Most common problem: Exposure

Initially, recommendations for “erosion” management were based on concerns about underlying mesh infection or rejection, and included a need to remove the entire graft. That recommendation still applies to multifilament, microporous grafts that present with inflammatory infiltrates, granulation tissue, and purulence. Although these kinds of grafts (known as “Type-2/3 grafts”—e.g., GoreTex, IVS) have not been marketed for pelvic reconstruction over the past 3 to 5 years, their behavior post-implantation is less predictable—and patients who have delayed healing abnormalities are, therefore, still being seen. It’s fortunate that development of an overlying biofilm prevents tissue incorporation into these types of graft, allowing them to be removed easily.

Exposures related to Type-1 mesh—currently used in pelvic reconstruction—that occur without surrounding infection do not require extensive removal. Rather, they can be managed conservatively or, when necessary, with outpatient surgery. In patients who are not sexually active, exposures are usually asymptomatic; they might only be observed by the physician on vaginal examination and are amenable to simple monitoring. In sexually active patients, exposure of Type-1 mesh usually results in dyspareunia or a complaint that the partner “can feel the mesh.” Depending on the size and the nature of symptoms and the extent of the defect, these commonly seen exposures can be managed by following a simple algorithm.

Palpable or visible mesh fibrils can be trimmed in the office; they might even respond to local estrogen alone. Consider these options if the patient displays vaginal atrophy.

Typically, vaginal estrogen is prescribed as 1 g nightly for 2 weeks and then 1 g two or three nights a week. Re-examine the patient in 3 months; if symptoms of mesh exposure persist, it’s unlikely that continued conservative therapy will be successful, and outpatient surgery is recommended.

When exposure is asymptomatic, you can simply monitor the condition for 3 to 6 months; if complaints or findings arise, consider intervention.

Small (<0.5 cm in diameter) exposures can also be managed in the office, including excision of exposed mesh and local estrogen. If the exposure is easily reachable, we recommend grasping the exposed area with pick-ups or a hemostat and with gentle traction, using Metzenbaum scissors to trim exposed mesh as close to the vaginal epithelium as possible. Local topical or injected anesthesia may be needed. Bleeding should be minimal because no dissection is necessary. Silver nitrate can be applied for any minor bleeding. Larger (0.5–4.0 cm) exposures are unlikely to heal on their own. They require outpatient excision in the operating room.

Preoperative tissue preparation with local estrogen is key to successful repair of these exposures. Vaginal estrogen increases blood flow to the epithelium; as tissue becomes well-estrogenized, risk of recurrence diminishes.

The technique we employ includes:

• circumferential infiltration of vaginal epithelium surrounding the exposed mesh with 1% lidocaine with epinephrine
• sharp circumscription of the area of exposure, using a scalpel, with a 0.5-cm margin of vaginal epithelium (FIGURE 2)
• wide dissection, with undermining and mobilization of surrounding healthy vaginal epithelium around the exposure (FIGURE 3)
• excision of the exposed mesh and attached vaginal mucosa, with careful dissection of the mesh off underlying tissues with Metzenbaum scissors—being careful to avoid injury to underlying bladder or rectum (FIGURE 4)
• reapproximation of mesh edges, using 2-0 polypropylene suture to close the resulting defect so that prolapse does not recur (FIGURE 5)
• closing of the previously mobilized vaginal epithelium with 2-0 Vicryl suture, without tension, to cover the reapproximated mesh edges—after irrigation and assurance of adequate hemostasis (FIGURE 6).

FIGURE 2 Incision of vaginal epithelium
Allow for a 0.5-cm margin.

FIGURE 3 Undermining and mobilization of epithelium
Perform wide dissection.

FIGURE 4 Dissection of mesh from underlying tissue
Keep clear of underlying bladder and rectum!

FIGURE 5 Reapproximation of edges to re-establish support
Our choice of suture is 2-0 polypropylene.

FIGURE 6 Irrigation of vaginal epithelium, followed by closure
Before you close, ensure that hemostasis is adequate.The choice of closure—vertical or horizontal—depends on the nature of the original defect.

You can watch a video of this technique that we’ve provided.

Several cautions should be taken with this technique, including:

• avoiding narrowing the vaginal canal
• minimizing trauma to healthy vaginal epithelium that will be used for closure
• maintaining hemostasis to avoid formation of hematomas.

Largest (>4 cm) exposures are likely the result of devascularized sloughing of vaginal epithelium. They are, fortunately, uncommon.

It’s unlikely that, after excision of exposed mesh, the vaginal epithelial edges can be approximated without significantly narrowing or shortening the vaginal canal. Proposed techniques for managing these large exposures include covering the defect with a biologic graft, such as small intestinal submucosa, to allow epithelium to re-grow. Regrettably, prolapse is likely to recur in the unprotected area that results.

Contraction and localized pain

Hardening and contraction typically occur along the fixation arms of the mesh. These complications might result from mesh shrinkage or from mesh being placed too tight, so to speak, at implantation. Rarely does the entire implanted mesh contract.

Severe mesh contraction can result in localized pain and de novo dyspareunia. Symptoms usually resolve after identification of the painful area and removal of the involved mesh segment.⁸

Diagnostic maneuver. In-office trigger-point injection of bupivacaine with triamcinolone is useful to accurately identify the location of pain that is causing dyspareunia. After injection, the patient is asked to return home and resume sexual intercourse; if dyspareunia diminishes significantly, surgical removal of the involved mesh segment is likely to ameliorate symptoms.

If dyspareunia persists after injection, however, the problem either 1) originates in a different location along the graft or 2) may not be related to the mesh—that is, it may be introital pain or preexisting vaginal pain.

The findings of trigger-point injection and a subsequent trial of sexual intercourse are useful for counseling the patient and developing realistic expectations that surgery will be successful.

Management note: Mesh contraction should be managed by a surgeon who is experienced in extensive deep pelvic dissection, which is necessary to remove the mesh arms.

Chronic pain

Diffuse vaginal pain after mesh implantation is unusual; typically, the patient’s report of pain has been preceded by recognition of another, underlying pelvic pain syndrome. Management of such pain is controversial, and many patients will not be satisfied until the entire graft is removed. Whether such drastic intervention actually resolves the pain is unclear; again, work with the patient to create realistic expectations before surgery—including the risk that prolapse will recur and that reoperation will be necessary.

Management note: An existing pelvic pain syndrome should be considered a relative contraindication to implantation of mesh.

Infection of the graft

Rarely, infection has been reported after implantation of Type-1 mesh—the result of either multi-microbial colonization or isolated infection by Bacteriodes melaninogenicus, Actinomyces spp, or Staphylococcus aureus. Untreated preoperative bacterial vaginitis is likely the underlying cause, and should be considered a contraindication to mesh implantation.

Typically, these patients complain of vaginal discharge and bleeding early postoperatively. Vaginal exposure of the mesh results from local inflammation and necrosis of tissue.

Management note: In these cases, it is necessary to 1) prescribe antimicrobial therapy that covers gram-negative and anaerobic bacteria and 2) undertake surgical removal of the exposed mesh, as we outlined above.⁹

Visceral erosion or fistula

Many experts believe that what is recorded as “erosion” of synthetic mesh into bladder or rectum is, in fact, a result of unrecognized visceral perforation at original implantation. This is a rare complication of mesh implantation.

Patients who experience mesh erosion into the bladder may have lower urinary-tract symptoms (LUTS) of urgency, frequency, dysuria, and hematuria. Any patient who reports de novo LUTS in the early postoperative period after a vaginal mesh procedure should receive office cystourethroscopy to ensure that no foreign body is present in the bladder or urethra.

Management note: Operative cystourethroscopy, with removal of exposed mesh, is the management of choice when mesh is found in the bladder or urethra.

Patients who have constant urinary or fecal incontinence immediately after surgery should be evaluated for vesicovaginal or rectovaginal fistula.

The presence of any of these complications necessitates removal of the involved mesh in its entirety, with concomitant repair of fistula. Typically, the procedures are performed by a specialist.

Our experience with correcting simple mesh exposures

During the past year at our tertiary referral center, 26 patients have undergone mesh revision because of exposure, using the technique we described above (FIGURE 2-6). The problem resolved in all; none had persistent dyspareunia. Many of these patients had already undergone attempts at correction of the exposure elsewhere—mostly, in the office, using techniques appropriate for that setting. Prolapse has not recurred in the 10 patients who required reapproximation of mesh edges because of a defect >2.5 cm.

CASE RESOLVED: Treatment, improvement

Under your care, the patient undergoes simplified outpatient excision of the exposed area of mesh. Mesh edges are reapproximated to support the resulting 3-cm defect.

At a 12-week postop visit, you note complete resolution of the exposure and normal vaginal caliber. The patient continues to apply estrogen cream and reports sustained improvement in sexual function.

For simple presentations, success is within reach

Simple mesh exposure can (as in the case we described) be managed by most gynecologists, utilizing the simple stepwise approach that we outlined above (for additional tips based on our experience, see “Pearls for avoiding mesh exposures”). In the case of more significant symptoms, de novo dyspareunia, visceral erosion, or fistula, however, referral to a specialist is warranted.

We want to hear from you! Tell us what you think.

CASE: Pain during intercourse, well after mesh implantation

Your patient, 61 years old, para 3, has come to your office by referral with a complaint of dyspareunia. The history includes placement of a synthetic vaginal mesh kit 14 months earlier for prolapse.

The medical record shows that the referring physician performed a “mesh excision” 1 year after the original procedure.

The woman reports that she is “very frustrated” that she is still dealing with this problem so long after the original procedure.

On examination, you note a 2.5-cm diameter area of exposed mesh in the anterior vagina, with healthy surrounding tissue and without inflammation or purulence (FIGURE 1). You are unable to reproduce her complaint of pain on vaginal examination.

What options can you offer to this woman? And will those options meet her therapeutic expectations?

FIGURE 1 Examination of your referred patient: Mesh is noticeably exposedThe recent increase in the use of mesh grafts to reconstruct pelvic anatomy has been directed mainly at improving surgical outcomes. Yet, at the same time, gynecologic surgeons find themselves facing a rise in associated complications of such surgery that they did not see previously.

Among the most troublesome and concerning of those complications are 1) exposure of mesh through the vaginal epithelium and 2) contraction or hardening of mesh (or both) that can result in dyspareunia and chronic pelvic pain. Other, rare complications include infection and fistula.

Our goal in this article is to address the management of graft-healing abnormalities in which a segment of the mesh is palpable or visible, or both, within the vaginal canal. Our focus is on simple abnormalities that can be managed by most generalist gynecologists; to be clear, more complex abnormalities, and those that provoke more serious or lasting symptoms, belong under the care of a specialist.

A recent shift in terminology is significant

Early on, this complication was called “erosion” as understanding of the mechanism of its development grew, however, terminology applied to the problem has changed.

In fact, mesh itself very rarely erodes into the vagina or an underlying viscus. Instead, the complication occurs most commonly as a result of disruption of a suture line—most likely the result of a hematoma or localized inflammation that develops postoperatively.

“Exposure” (our preference here) and “extrusion” are now the recommended terms, based on a consensus terminology document published this year jointly by the International Urogynecological Association and the International Continence Society.¹

Exposure of implanted mesh is considered a “simple” healing abnormality because it typically

• occurs along the suture line and early in the course of healing
• is not associated with infection of the graft.²

The typical physical appearance is one of visible mesh along an open suture line without granulation tissue or purulence—again, see FIGURE 1. The mesh is firmly adherent to the vaginal epithelial edges and underlying fascia.

The reported incidence of mesh exposures—in regard to currently used meshes, which are all Type-1, monofilament, macroporous polypropylene grafts—is approximately 10% but as high as 15% to 20% in some reported series.^3,4 The higher rates of exposure are usually seen in series in which some patients have had a synthetic graft implanted as an overlay to fascial midline plication. When the graft is implanted in the subfascial layer of the vaginal wall (i.e., without midline plication), however, the reported rate of exposure falls—to 5% to 10%.^5-7

Recommendations for management

Most common problem: Exposure

Initially, recommendations for “erosion” management were based on concerns about underlying mesh infection or rejection, and included a need to remove the entire graft. That recommendation still applies to multifilament, microporous grafts that present with inflammatory infiltrates, granulation tissue, and purulence. Although these kinds of grafts (known as “Type-2/3 grafts”—e.g., GoreTex, IVS) have not been marketed for pelvic reconstruction over the past 3 to 5 years, their behavior post-implantation is less predictable—and patients who have delayed healing abnormalities are, therefore, still being seen. It’s fortunate that development of an overlying biofilm prevents tissue incorporation into these types of graft, allowing them to be removed easily.

Exposures related to Type-1 mesh—currently used in pelvic reconstruction—that occur without surrounding infection do not require extensive removal. Rather, they can be managed conservatively or, when necessary, with outpatient surgery. In patients who are not sexually active, exposures are usually asymptomatic; they might only be observed by the physician on vaginal examination and are amenable to simple monitoring. In sexually active patients, exposure of Type-1 mesh usually results in dyspareunia or a complaint that the partner “can feel the mesh.” Depending on the size and the nature of symptoms and the extent of the defect, these commonly seen exposures can be managed by following a simple algorithm.

Palpable or visible mesh fibrils can be trimmed in the office; they might even respond to local estrogen alone. Consider these options if the patient displays vaginal atrophy.

Typically, vaginal estrogen is prescribed as 1 g nightly for 2 weeks and then 1 g two or three nights a week. Re-examine the patient in 3 months; if symptoms of mesh exposure persist, it’s unlikely that continued conservative therapy will be successful, and outpatient surgery is recommended.

When exposure is asymptomatic, you can simply monitor the condition for 3 to 6 months; if complaints or findings arise, consider intervention.

Small (<0.5 cm in diameter) exposures can also be managed in the office, including excision of exposed mesh and local estrogen. If the exposure is easily reachable, we recommend grasping the exposed area with pick-ups or a hemostat and with gentle traction, using Metzenbaum scissors to trim exposed mesh as close to the vaginal epithelium as possible. Local topical or injected anesthesia may be needed. Bleeding should be minimal because no dissection is necessary. Silver nitrate can be applied for any minor bleeding. Larger (0.5–4.0 cm) exposures are unlikely to heal on their own. They require outpatient excision in the operating room.

Preoperative tissue preparation with local estrogen is key to successful repair of these exposures. Vaginal estrogen increases blood flow to the epithelium; as tissue becomes well-estrogenized, risk of recurrence diminishes.

The technique we employ includes:

• circumferential infiltration of vaginal epithelium surrounding the exposed mesh with 1% lidocaine with epinephrine
• sharp circumscription of the area of exposure, using a scalpel, with a 0.5-cm margin of vaginal epithelium (FIGURE 2)
• wide dissection, with undermining and mobilization of surrounding healthy vaginal epithelium around the exposure (FIGURE 3)
• excision of the exposed mesh and attached vaginal mucosa, with careful dissection of the mesh off underlying tissues with Metzenbaum scissors—being careful to avoid injury to underlying bladder or rectum (FIGURE 4)
• reapproximation of mesh edges, using 2-0 polypropylene suture to close the resulting defect so that prolapse does not recur (FIGURE 5)
• closing of the previously mobilized vaginal epithelium with 2-0 Vicryl suture, without tension, to cover the reapproximated mesh edges—after irrigation and assurance of adequate hemostasis (FIGURE 6).

FIGURE 2 Incision of vaginal epithelium
Allow for a 0.5-cm margin.

FIGURE 3 Undermining and mobilization of epithelium
Perform wide dissection.

FIGURE 4 Dissection of mesh from underlying tissue
Keep clear of underlying bladder and rectum!

FIGURE 5 Reapproximation of edges to re-establish support
Our choice of suture is 2-0 polypropylene.

FIGURE 6 Irrigation of vaginal epithelium, followed by closure
Before you close, ensure that hemostasis is adequate.The choice of closure—vertical or horizontal—depends on the nature of the original defect.

You can watch a video of this technique that we’ve provided.

Several cautions should be taken with this technique, including:

• avoiding narrowing the vaginal canal
• minimizing trauma to healthy vaginal epithelium that will be used for closure
• maintaining hemostasis to avoid formation of hematomas.

Largest (>4 cm) exposures are likely the result of devascularized sloughing of vaginal epithelium. They are, fortunately, uncommon.

It’s unlikely that, after excision of exposed mesh, the vaginal epithelial edges can be approximated without significantly narrowing or shortening the vaginal canal. Proposed techniques for managing these large exposures include covering the defect with a biologic graft, such as small intestinal submucosa, to allow epithelium to re-grow. Regrettably, prolapse is likely to recur in the unprotected area that results.

Contraction and localized pain

Hardening and contraction typically occur along the fixation arms of the mesh. These complications might result from mesh shrinkage or from mesh being placed too tight, so to speak, at implantation. Rarely does the entire implanted mesh contract.

Severe mesh contraction can result in localized pain and de novo dyspareunia. Symptoms usually resolve after identification of the painful area and removal of the involved mesh segment.⁸

Diagnostic maneuver. In-office trigger-point injection of bupivacaine with triamcinolone is useful to accurately identify the location of pain that is causing dyspareunia. After injection, the patient is asked to return home and resume sexual intercourse; if dyspareunia diminishes significantly, surgical removal of the involved mesh segment is likely to ameliorate symptoms.

If dyspareunia persists after injection, however, the problem either 1) originates in a different location along the graft or 2) may not be related to the mesh—that is, it may be introital pain or preexisting vaginal pain.

The findings of trigger-point injection and a subsequent trial of sexual intercourse are useful for counseling the patient and developing realistic expectations that surgery will be successful.

Management note: Mesh contraction should be managed by a surgeon who is experienced in extensive deep pelvic dissection, which is necessary to remove the mesh arms.

Chronic pain

Diffuse vaginal pain after mesh implantation is unusual; typically, the patient’s report of pain has been preceded by recognition of another, underlying pelvic pain syndrome. Management of such pain is controversial, and many patients will not be satisfied until the entire graft is removed. Whether such drastic intervention actually resolves the pain is unclear; again, work with the patient to create realistic expectations before surgery—including the risk that prolapse will recur and that reoperation will be necessary.

Management note: An existing pelvic pain syndrome should be considered a relative contraindication to implantation of mesh.

Infection of the graft

Rarely, infection has been reported after implantation of Type-1 mesh—the result of either multi-microbial colonization or isolated infection by Bacteriodes melaninogenicus, Actinomyces spp, or Staphylococcus aureus. Untreated preoperative bacterial vaginitis is likely the underlying cause, and should be considered a contraindication to mesh implantation.

Typically, these patients complain of vaginal discharge and bleeding early postoperatively. Vaginal exposure of the mesh results from local inflammation and necrosis of tissue.

Management note: In these cases, it is necessary to 1) prescribe antimicrobial therapy that covers gram-negative and anaerobic bacteria and 2) undertake surgical removal of the exposed mesh, as we outlined above.⁹

Visceral erosion or fistula

Many experts believe that what is recorded as “erosion” of synthetic mesh into bladder or rectum is, in fact, a result of unrecognized visceral perforation at original implantation. This is a rare complication of mesh implantation.

Patients who experience mesh erosion into the bladder may have lower urinary-tract symptoms (LUTS) of urgency, frequency, dysuria, and hematuria. Any patient who reports de novo LUTS in the early postoperative period after a vaginal mesh procedure should receive office cystourethroscopy to ensure that no foreign body is present in the bladder or urethra.

Management note: Operative cystourethroscopy, with removal of exposed mesh, is the management of choice when mesh is found in the bladder or urethra.

Patients who have constant urinary or fecal incontinence immediately after surgery should be evaluated for vesicovaginal or rectovaginal fistula.

The presence of any of these complications necessitates removal of the involved mesh in its entirety, with concomitant repair of fistula. Typically, the procedures are performed by a specialist.

Our experience with correcting simple mesh exposures

During the past year at our tertiary referral center, 26 patients have undergone mesh revision because of exposure, using the technique we described above (FIGURE 2-6). The problem resolved in all; none had persistent dyspareunia. Many of these patients had already undergone attempts at correction of the exposure elsewhere—mostly, in the office, using techniques appropriate for that setting. Prolapse has not recurred in the 10 patients who required reapproximation of mesh edges because of a defect >2.5 cm.

CASE RESOLVED: Treatment, improvement

Under your care, the patient undergoes simplified outpatient excision of the exposed area of mesh. Mesh edges are reapproximated to support the resulting 3-cm defect.

At a 12-week postop visit, you note complete resolution of the exposure and normal vaginal caliber. The patient continues to apply estrogen cream and reports sustained improvement in sexual function.

For simple presentations, success is within reach

Simple mesh exposure can (as in the case we described) be managed by most gynecologists, utilizing the simple stepwise approach that we outlined above (for additional tips based on our experience, see “Pearls for avoiding mesh exposures”). In the case of more significant symptoms, de novo dyspareunia, visceral erosion, or fistula, however, referral to a specialist is warranted.

We want to hear from you! Tell us what you think.

CASE: Pain during intercourse, well after mesh implantation

Your patient, 61 years old, para 3, has come to your office by referral with a complaint of dyspareunia. The history includes placement of a synthetic vaginal mesh kit 14 months earlier for prolapse.

The medical record shows that the referring physician performed a “mesh excision” 1 year after the original procedure.

The woman reports that she is “very frustrated” that she is still dealing with this problem so long after the original procedure.

On examination, you note a 2.5-cm diameter area of exposed mesh in the anterior vagina, with healthy surrounding tissue and without inflammation or purulence (FIGURE 1). You are unable to reproduce her complaint of pain on vaginal examination.

What options can you offer to this woman? And will those options meet her therapeutic expectations?

FIGURE 1 Examination of your referred patient: Mesh is noticeably exposedThe recent increase in the use of mesh grafts to reconstruct pelvic anatomy has been directed mainly at improving surgical outcomes. Yet, at the same time, gynecologic surgeons find themselves facing a rise in associated complications of such surgery that they did not see previously.

Among the most troublesome and concerning of those complications are 1) exposure of mesh through the vaginal epithelium and 2) contraction or hardening of mesh (or both) that can result in dyspareunia and chronic pelvic pain. Other, rare complications include infection and fistula.

Our goal in this article is to address the management of graft-healing abnormalities in which a segment of the mesh is palpable or visible, or both, within the vaginal canal. Our focus is on simple abnormalities that can be managed by most generalist gynecologists; to be clear, more complex abnormalities, and those that provoke more serious or lasting symptoms, belong under the care of a specialist.

A recent shift in terminology is significant

Early on, this complication was called “erosion” as understanding of the mechanism of its development grew, however, terminology applied to the problem has changed.

In fact, mesh itself very rarely erodes into the vagina or an underlying viscus. Instead, the complication occurs most commonly as a result of disruption of a suture line—most likely the result of a hematoma or localized inflammation that develops postoperatively.

“Exposure” (our preference here) and “extrusion” are now the recommended terms, based on a consensus terminology document published this year jointly by the International Urogynecological Association and the International Continence Society.¹

Exposure of implanted mesh is considered a “simple” healing abnormality because it typically

• occurs along the suture line and early in the course of healing
• is not associated with infection of the graft.²

The typical physical appearance is one of visible mesh along an open suture line without granulation tissue or purulence—again, see FIGURE 1. The mesh is firmly adherent to the vaginal epithelial edges and underlying fascia.

The reported incidence of mesh exposures—in regard to currently used meshes, which are all Type-1, monofilament, macroporous polypropylene grafts—is approximately 10% but as high as 15% to 20% in some reported series.^3,4 The higher rates of exposure are usually seen in series in which some patients have had a synthetic graft implanted as an overlay to fascial midline plication. When the graft is implanted in the subfascial layer of the vaginal wall (i.e., without midline plication), however, the reported rate of exposure falls—to 5% to 10%.^5-7

Recommendations for management

Most common problem: Exposure

Initially, recommendations for “erosion” management were based on concerns about underlying mesh infection or rejection, and included a need to remove the entire graft. That recommendation still applies to multifilament, microporous grafts that present with inflammatory infiltrates, granulation tissue, and purulence. Although these kinds of grafts (known as “Type-2/3 grafts”—e.g., GoreTex, IVS) have not been marketed for pelvic reconstruction over the past 3 to 5 years, their behavior post-implantation is less predictable—and patients who have delayed healing abnormalities are, therefore, still being seen. It’s fortunate that development of an overlying biofilm prevents tissue incorporation into these types of graft, allowing them to be removed easily.

Exposures related to Type-1 mesh—currently used in pelvic reconstruction—that occur without surrounding infection do not require extensive removal. Rather, they can be managed conservatively or, when necessary, with outpatient surgery. In patients who are not sexually active, exposures are usually asymptomatic; they might only be observed by the physician on vaginal examination and are amenable to simple monitoring. In sexually active patients, exposure of Type-1 mesh usually results in dyspareunia or a complaint that the partner “can feel the mesh.” Depending on the size and the nature of symptoms and the extent of the defect, these commonly seen exposures can be managed by following a simple algorithm.

Palpable or visible mesh fibrils can be trimmed in the office; they might even respond to local estrogen alone. Consider these options if the patient displays vaginal atrophy.

Typically, vaginal estrogen is prescribed as 1 g nightly for 2 weeks and then 1 g two or three nights a week. Re-examine the patient in 3 months; if symptoms of mesh exposure persist, it’s unlikely that continued conservative therapy will be successful, and outpatient surgery is recommended.

When exposure is asymptomatic, you can simply monitor the condition for 3 to 6 months; if complaints or findings arise, consider intervention.

Small (<0.5 cm in diameter) exposures can also be managed in the office, including excision of exposed mesh and local estrogen. If the exposure is easily reachable, we recommend grasping the exposed area with pick-ups or a hemostat and with gentle traction, using Metzenbaum scissors to trim exposed mesh as close to the vaginal epithelium as possible. Local topical or injected anesthesia may be needed. Bleeding should be minimal because no dissection is necessary. Silver nitrate can be applied for any minor bleeding. Larger (0.5–4.0 cm) exposures are unlikely to heal on their own. They require outpatient excision in the operating room.

Preoperative tissue preparation with local estrogen is key to successful repair of these exposures. Vaginal estrogen increases blood flow to the epithelium; as tissue becomes well-estrogenized, risk of recurrence diminishes.

The technique we employ includes:

• circumferential infiltration of vaginal epithelium surrounding the exposed mesh with 1% lidocaine with epinephrine
• sharp circumscription of the area of exposure, using a scalpel, with a 0.5-cm margin of vaginal epithelium (FIGURE 2)
• wide dissection, with undermining and mobilization of surrounding healthy vaginal epithelium around the exposure (FIGURE 3)
• excision of the exposed mesh and attached vaginal mucosa, with careful dissection of the mesh off underlying tissues with Metzenbaum scissors—being careful to avoid injury to underlying bladder or rectum (FIGURE 4)
• reapproximation of mesh edges, using 2-0 polypropylene suture to close the resulting defect so that prolapse does not recur (FIGURE 5)
• closing of the previously mobilized vaginal epithelium with 2-0 Vicryl suture, without tension, to cover the reapproximated mesh edges—after irrigation and assurance of adequate hemostasis (FIGURE 6).

FIGURE 2 Incision of vaginal epithelium
Allow for a 0.5-cm margin.

FIGURE 3 Undermining and mobilization of epithelium
Perform wide dissection.

FIGURE 4 Dissection of mesh from underlying tissue
Keep clear of underlying bladder and rectum!

FIGURE 5 Reapproximation of edges to re-establish support
Our choice of suture is 2-0 polypropylene.

FIGURE 6 Irrigation of vaginal epithelium, followed by closure
Before you close, ensure that hemostasis is adequate.The choice of closure—vertical or horizontal—depends on the nature of the original defect.

You can watch a video of this technique that we’ve provided.

Several cautions should be taken with this technique, including:

• avoiding narrowing the vaginal canal
• minimizing trauma to healthy vaginal epithelium that will be used for closure
• maintaining hemostasis to avoid formation of hematomas.

Largest (>4 cm) exposures are likely the result of devascularized sloughing of vaginal epithelium. They are, fortunately, uncommon.

It’s unlikely that, after excision of exposed mesh, the vaginal epithelial edges can be approximated without significantly narrowing or shortening the vaginal canal. Proposed techniques for managing these large exposures include covering the defect with a biologic graft, such as small intestinal submucosa, to allow epithelium to re-grow. Regrettably, prolapse is likely to recur in the unprotected area that results.

Contraction and localized pain

Hardening and contraction typically occur along the fixation arms of the mesh. These complications might result from mesh shrinkage or from mesh being placed too tight, so to speak, at implantation. Rarely does the entire implanted mesh contract.

Severe mesh contraction can result in localized pain and de novo dyspareunia. Symptoms usually resolve after identification of the painful area and removal of the involved mesh segment.⁸

Diagnostic maneuver. In-office trigger-point injection of bupivacaine with triamcinolone is useful to accurately identify the location of pain that is causing dyspareunia. After injection, the patient is asked to return home and resume sexual intercourse; if dyspareunia diminishes significantly, surgical removal of the involved mesh segment is likely to ameliorate symptoms.

If dyspareunia persists after injection, however, the problem either 1) originates in a different location along the graft or 2) may not be related to the mesh—that is, it may be introital pain or preexisting vaginal pain.

The findings of trigger-point injection and a subsequent trial of sexual intercourse are useful for counseling the patient and developing realistic expectations that surgery will be successful.

Management note: Mesh contraction should be managed by a surgeon who is experienced in extensive deep pelvic dissection, which is necessary to remove the mesh arms.

Chronic pain

Diffuse vaginal pain after mesh implantation is unusual; typically, the patient’s report of pain has been preceded by recognition of another, underlying pelvic pain syndrome. Management of such pain is controversial, and many patients will not be satisfied until the entire graft is removed. Whether such drastic intervention actually resolves the pain is unclear; again, work with the patient to create realistic expectations before surgery—including the risk that prolapse will recur and that reoperation will be necessary.

Management note: An existing pelvic pain syndrome should be considered a relative contraindication to implantation of mesh.

Infection of the graft

Rarely, infection has been reported after implantation of Type-1 mesh—the result of either multi-microbial colonization or isolated infection by Bacteriodes melaninogenicus, Actinomyces spp, or Staphylococcus aureus. Untreated preoperative bacterial vaginitis is likely the underlying cause, and should be considered a contraindication to mesh implantation.

Typically, these patients complain of vaginal discharge and bleeding early postoperatively. Vaginal exposure of the mesh results from local inflammation and necrosis of tissue.

Management note: In these cases, it is necessary to 1) prescribe antimicrobial therapy that covers gram-negative and anaerobic bacteria and 2) undertake surgical removal of the exposed mesh, as we outlined above.⁹

Visceral erosion or fistula

Many experts believe that what is recorded as “erosion” of synthetic mesh into bladder or rectum is, in fact, a result of unrecognized visceral perforation at original implantation. This is a rare complication of mesh implantation.

Patients who experience mesh erosion into the bladder may have lower urinary-tract symptoms (LUTS) of urgency, frequency, dysuria, and hematuria. Any patient who reports de novo LUTS in the early postoperative period after a vaginal mesh procedure should receive office cystourethroscopy to ensure that no foreign body is present in the bladder or urethra.

Management note: Operative cystourethroscopy, with removal of exposed mesh, is the management of choice when mesh is found in the bladder or urethra.

Patients who have constant urinary or fecal incontinence immediately after surgery should be evaluated for vesicovaginal or rectovaginal fistula.

The presence of any of these complications necessitates removal of the involved mesh in its entirety, with concomitant repair of fistula. Typically, the procedures are performed by a specialist.

Our experience with correcting simple mesh exposures

During the past year at our tertiary referral center, 26 patients have undergone mesh revision because of exposure, using the technique we described above (FIGURE 2-6). The problem resolved in all; none had persistent dyspareunia. Many of these patients had already undergone attempts at correction of the exposure elsewhere—mostly, in the office, using techniques appropriate for that setting. Prolapse has not recurred in the 10 patients who required reapproximation of mesh edges because of a defect >2.5 cm.

CASE RESOLVED: Treatment, improvement

Under your care, the patient undergoes simplified outpatient excision of the exposed area of mesh. Mesh edges are reapproximated to support the resulting 3-cm defect.

At a 12-week postop visit, you note complete resolution of the exposure and normal vaginal caliber. The patient continues to apply estrogen cream and reports sustained improvement in sexual function.

For simple presentations, success is within reach

Simple mesh exposure can (as in the case we described) be managed by most gynecologists, utilizing the simple stepwise approach that we outlined above (for additional tips based on our experience, see “Pearls for avoiding mesh exposures”). In the case of more significant symptoms, de novo dyspareunia, visceral erosion, or fistula, however, referral to a specialist is warranted.

We want to hear from you! Tell us what you think.

Although eating disorders can be life-threatening,¹ many patients remain undiagnosed until late in the disease course. Early identification and treatment may reduce the risk of chronic health consequences and mortality.

Based on the DSM-IV-TR categorical approach, many clinicians think of anorexia nervosa and bulimia nervosa as the primary eating disorders. However, eating disorder not otherwise specified tends to be the most common diagnosis.² Several authors have suggested that combining categorical and dimensional approaches may be useful in diagnosing these patients.²

It is easy to suspect an eating disorder in patients of very low weight, but patients who are of normal weight or obese also may have an eating disorder. In addition to measuring body mass index, inquire about patients’ lowest and highest adult, nonpregnant weights and what they consider to be their “ideal” weight. The mnemonic ABCDE can help you remember key components of assessing patients who might have an eating disorder.

Associated health problems. Anorexia patients commonly present with emaciation, skin and hair dryness, cold intolerance, bradycardia, and orthostatic hypotension. Look for calluses on dorsum of the hands, parotid enlargement, mouth ulcers, dental caries, and edema, which may be found in bulimia patients.

Body image. Determine whether your patients’ self esteem is correlated with body weight and shape, how often they weigh themselves, and if they are satisfied with the way their body is proportioned. Ask if they fear weight gain or are driven to be thin.

Compensatory behaviors may include self-induced vomiting or excessive use of diet pills, diuretics, or laxatives. Other examples are restricting food, chewing and spitting out food, and over-exercising (especially lengthy cardiovascular workouts).

Diet. Inquire whether your patients have ever been on a diet, reduced the amount of food they consume, or used medications indicated for obesity. Patients may avoid entire categories of foods (lipids, carbohydrates), which may lead to malnutrition and vitamin deficiencies.

Eating behaviors. Patients may eat very small meals or excessive portions of certain foods. They might skip meals or eat only alone or at night. Finishing meals very slowly or very quickly, mixing food on their plate, eating with tiny bites, or drinking a lot of water with and between meals also may be clues to disordered eating. None of these behaviors by itself indicate an eating disorder if not accompanied by other symptoms.

Disclosure

The authors report no financial relationship with any manufacturer whose products are mentioned in this article or with manufacturers of competing products.

Although eating disorders can be life-threatening,¹ many patients remain undiagnosed until late in the disease course. Early identification and treatment may reduce the risk of chronic health consequences and mortality.

Based on the DSM-IV-TR categorical approach, many clinicians think of anorexia nervosa and bulimia nervosa as the primary eating disorders. However, eating disorder not otherwise specified tends to be the most common diagnosis.² Several authors have suggested that combining categorical and dimensional approaches may be useful in diagnosing these patients.²

It is easy to suspect an eating disorder in patients of very low weight, but patients who are of normal weight or obese also may have an eating disorder. In addition to measuring body mass index, inquire about patients’ lowest and highest adult, nonpregnant weights and what they consider to be their “ideal” weight. The mnemonic ABCDE can help you remember key components of assessing patients who might have an eating disorder.

Associated health problems. Anorexia patients commonly present with emaciation, skin and hair dryness, cold intolerance, bradycardia, and orthostatic hypotension. Look for calluses on dorsum of the hands, parotid enlargement, mouth ulcers, dental caries, and edema, which may be found in bulimia patients.

Body image. Determine whether your patients’ self esteem is correlated with body weight and shape, how often they weigh themselves, and if they are satisfied with the way their body is proportioned. Ask if they fear weight gain or are driven to be thin.

Compensatory behaviors may include self-induced vomiting or excessive use of diet pills, diuretics, or laxatives. Other examples are restricting food, chewing and spitting out food, and over-exercising (especially lengthy cardiovascular workouts).

Diet. Inquire whether your patients have ever been on a diet, reduced the amount of food they consume, or used medications indicated for obesity. Patients may avoid entire categories of foods (lipids, carbohydrates), which may lead to malnutrition and vitamin deficiencies.

Eating behaviors. Patients may eat very small meals or excessive portions of certain foods. They might skip meals or eat only alone or at night. Finishing meals very slowly or very quickly, mixing food on their plate, eating with tiny bites, or drinking a lot of water with and between meals also may be clues to disordered eating. None of these behaviors by itself indicate an eating disorder if not accompanied by other symptoms.

Disclosure

The authors report no financial relationship with any manufacturer whose products are mentioned in this article or with manufacturers of competing products.

Although eating disorders can be life-threatening,¹ many patients remain undiagnosed until late in the disease course. Early identification and treatment may reduce the risk of chronic health consequences and mortality.

Based on the DSM-IV-TR categorical approach, many clinicians think of anorexia nervosa and bulimia nervosa as the primary eating disorders. However, eating disorder not otherwise specified tends to be the most common diagnosis.² Several authors have suggested that combining categorical and dimensional approaches may be useful in diagnosing these patients.²

It is easy to suspect an eating disorder in patients of very low weight, but patients who are of normal weight or obese also may have an eating disorder. In addition to measuring body mass index, inquire about patients’ lowest and highest adult, nonpregnant weights and what they consider to be their “ideal” weight. The mnemonic ABCDE can help you remember key components of assessing patients who might have an eating disorder.

Associated health problems. Anorexia patients commonly present with emaciation, skin and hair dryness, cold intolerance, bradycardia, and orthostatic hypotension. Look for calluses on dorsum of the hands, parotid enlargement, mouth ulcers, dental caries, and edema, which may be found in bulimia patients.

Body image. Determine whether your patients’ self esteem is correlated with body weight and shape, how often they weigh themselves, and if they are satisfied with the way their body is proportioned. Ask if they fear weight gain or are driven to be thin.

Compensatory behaviors may include self-induced vomiting or excessive use of diet pills, diuretics, or laxatives. Other examples are restricting food, chewing and spitting out food, and over-exercising (especially lengthy cardiovascular workouts).

Diet. Inquire whether your patients have ever been on a diet, reduced the amount of food they consume, or used medications indicated for obesity. Patients may avoid entire categories of foods (lipids, carbohydrates), which may lead to malnutrition and vitamin deficiencies.

Eating behaviors. Patients may eat very small meals or excessive portions of certain foods. They might skip meals or eat only alone or at night. Finishing meals very slowly or very quickly, mixing food on their plate, eating with tiny bites, or drinking a lot of water with and between meals also may be clues to disordered eating. None of these behaviors by itself indicate an eating disorder if not accompanied by other symptoms.

Disclosure

The authors report no financial relationship with any manufacturer whose products are mentioned in this article or with manufacturers of competing products.