Neurology

Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

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Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Decreased time in deep, dreamless sleep is associated with increasing Alzheimer’s disease pathology. Also today, physician groups are pushing back on Part B of the drug reimbursement proposal, dabigatran matches aspirin for second stroke prevention, and reassurance for pregnancy in atopic dermatitis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.

Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.

“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.

Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.

The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.

The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.

Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).

Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.

Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.

Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.

“Developmentally, [children] may be unable to verbally express the side effects they are feeling and may therefore be subject to a drug to treat a drug side effect, especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.

This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.

“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.

They reported having no disclosures.

[email protected]

SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.

Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?

►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.

►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?

►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.¹ In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.

►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1). 

Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?

►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.

►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.

Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?

►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.²

►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?

►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.

►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2). 

Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?

►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.^3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.

►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer. 

Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?

►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.⁵ The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.⁶

►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?

►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.⁷

►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.

This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.

Acknowledgments

We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.

Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?

►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.

►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?

►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.¹ In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.

►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1). 

Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?

►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.

►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.

Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?

►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.²

►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?

►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.

►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2). 

Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?

►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.^3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.

►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer. 

Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?

►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.⁵ The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.⁶

►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?

►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.⁷

►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.

This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.

Acknowledgments

We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.

Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?

►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.

►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?

►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.¹ In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.

►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1). 

Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?

►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.

►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.

Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?

►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.²

►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?

►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.

►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2). 

Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?

►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.^3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.

►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer. 

Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?

►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.⁵ The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.⁶

►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?

►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.⁷

►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.

This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.

Acknowledgments

We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.

NEW ORLEANS – The onset of pediatric refractory status epilepticus follows a circadian pattern, according to research presented at the annual meeting of the American Epilepsy Society. The number of episodes is greatest between 10 a.m. and 11 a.m. and smallest between 10 p.m. and 11 p.m.

“Our findings may inform the increase in preventive monitoring, such as video monitoring or seizure-tracking devices for patients,” said Justice Clark, MPH, a program coordinator at Boston Children’s Hospital. “They may also inform chronotherapeutic strategies.”

Research suggests that various types of seizures cluster at different times of the day. Data about the circadian distribution of status epilepticus, however, are limited.

Ms. Clark and colleagues conducted a prospective observational study at 25 hospitals in the United States and Canada from June 2011 to January 2018. Eligible participants were between ages 1 month and 21 years, had focal or generalized convulsive status epilepticus, and had failed to respond to one benzodiazepine and one nonbenzodiazepine antiseizure medication. For patients with more than one episode of refractory status epilepticus during the study, the researchers included only the first episode.

The investigators examined whether the temporal distribution of pediatric refractory status epilepticus onset followed a circadian pattern using a cosinor analysis with a 12-hour cycle. They used the midline-estimating statistic of rhythm (MESOR) technique to estimate the mean number of refractory status epilepticus episodes per hour if onset was evenly distributed. The amplitude in this analysis was the difference in number of episodes per hour between the MESOR and the peak or the MESOR and the trough.

Ms. Clark and her colleagues included 300 patients in their analysis, each of whom had one episode. Approximately 45% of participants were female. The population’s median age was 4.2 years, and the median duration of status epilepticus was 120 minutes.

The MESOR was 12.5 episodes per hour, and the amplitude was 2.4 episodes per hour, indicating that the distribution was not even over 24 hours. The peak number of onsets was between 10 a.m. and 11 a.m., and the trough was between 10 p.m. and 11 p.m.

A secondary analysis examined the circadian distribution of time to treatment with rescue medications. The distribution of time to treatment with the first benzodiazepine did not differ significantly from a uniform distribution. The time to treatment with the first nonbenzodiazepine antiseizure medication, however, was not uniformly distributed. The longest time to treatment occurred between 3 a.m. and 4 a.m., and the shortest time was between 3 p.m. and 4 p.m. “Although fewer refractory status epilepticus episodes occurred at night, the time to antiseizure medication administration was the longest [during that period]. Thus, nighttime refractory status epilepticus episodes may be at higher risk for delayed treatment,” said Ms. Clark. A limitation of this analysis is that it was influenced by outliers, she added.

The Pediatric Epilepsy Research Foundation and the Epilepsy Research Fund supported the study.

[email protected]

SOURCE: Clark J et al. AES 2018. Abstract 3.426.

NEW ORLEANS – The onset of pediatric refractory status epilepticus follows a circadian pattern, according to research presented at the annual meeting of the American Epilepsy Society. The number of episodes is greatest between 10 a.m. and 11 a.m. and smallest between 10 p.m. and 11 p.m.

“Our findings may inform the increase in preventive monitoring, such as video monitoring or seizure-tracking devices for patients,” said Justice Clark, MPH, a program coordinator at Boston Children’s Hospital. “They may also inform chronotherapeutic strategies.”

Research suggests that various types of seizures cluster at different times of the day. Data about the circadian distribution of status epilepticus, however, are limited.

Ms. Clark and colleagues conducted a prospective observational study at 25 hospitals in the United States and Canada from June 2011 to January 2018. Eligible participants were between ages 1 month and 21 years, had focal or generalized convulsive status epilepticus, and had failed to respond to one benzodiazepine and one nonbenzodiazepine antiseizure medication. For patients with more than one episode of refractory status epilepticus during the study, the researchers included only the first episode.

The investigators examined whether the temporal distribution of pediatric refractory status epilepticus onset followed a circadian pattern using a cosinor analysis with a 12-hour cycle. They used the midline-estimating statistic of rhythm (MESOR) technique to estimate the mean number of refractory status epilepticus episodes per hour if onset was evenly distributed. The amplitude in this analysis was the difference in number of episodes per hour between the MESOR and the peak or the MESOR and the trough.

Ms. Clark and her colleagues included 300 patients in their analysis, each of whom had one episode. Approximately 45% of participants were female. The population’s median age was 4.2 years, and the median duration of status epilepticus was 120 minutes.

The MESOR was 12.5 episodes per hour, and the amplitude was 2.4 episodes per hour, indicating that the distribution was not even over 24 hours. The peak number of onsets was between 10 a.m. and 11 a.m., and the trough was between 10 p.m. and 11 p.m.

A secondary analysis examined the circadian distribution of time to treatment with rescue medications. The distribution of time to treatment with the first benzodiazepine did not differ significantly from a uniform distribution. The time to treatment with the first nonbenzodiazepine antiseizure medication, however, was not uniformly distributed. The longest time to treatment occurred between 3 a.m. and 4 a.m., and the shortest time was between 3 p.m. and 4 p.m. “Although fewer refractory status epilepticus episodes occurred at night, the time to antiseizure medication administration was the longest [during that period]. Thus, nighttime refractory status epilepticus episodes may be at higher risk for delayed treatment,” said Ms. Clark. A limitation of this analysis is that it was influenced by outliers, she added.

The Pediatric Epilepsy Research Foundation and the Epilepsy Research Fund supported the study.

[email protected]

SOURCE: Clark J et al. AES 2018. Abstract 3.426.

NEW ORLEANS – The onset of pediatric refractory status epilepticus follows a circadian pattern, according to research presented at the annual meeting of the American Epilepsy Society. The number of episodes is greatest between 10 a.m. and 11 a.m. and smallest between 10 p.m. and 11 p.m.

“Our findings may inform the increase in preventive monitoring, such as video monitoring or seizure-tracking devices for patients,” said Justice Clark, MPH, a program coordinator at Boston Children’s Hospital. “They may also inform chronotherapeutic strategies.”

Research suggests that various types of seizures cluster at different times of the day. Data about the circadian distribution of status epilepticus, however, are limited.

Ms. Clark and colleagues conducted a prospective observational study at 25 hospitals in the United States and Canada from June 2011 to January 2018. Eligible participants were between ages 1 month and 21 years, had focal or generalized convulsive status epilepticus, and had failed to respond to one benzodiazepine and one nonbenzodiazepine antiseizure medication. For patients with more than one episode of refractory status epilepticus during the study, the researchers included only the first episode.

The investigators examined whether the temporal distribution of pediatric refractory status epilepticus onset followed a circadian pattern using a cosinor analysis with a 12-hour cycle. They used the midline-estimating statistic of rhythm (MESOR) technique to estimate the mean number of refractory status epilepticus episodes per hour if onset was evenly distributed. The amplitude in this analysis was the difference in number of episodes per hour between the MESOR and the peak or the MESOR and the trough.

Ms. Clark and her colleagues included 300 patients in their analysis, each of whom had one episode. Approximately 45% of participants were female. The population’s median age was 4.2 years, and the median duration of status epilepticus was 120 minutes.

The MESOR was 12.5 episodes per hour, and the amplitude was 2.4 episodes per hour, indicating that the distribution was not even over 24 hours. The peak number of onsets was between 10 a.m. and 11 a.m., and the trough was between 10 p.m. and 11 p.m.

A secondary analysis examined the circadian distribution of time to treatment with rescue medications. The distribution of time to treatment with the first benzodiazepine did not differ significantly from a uniform distribution. The time to treatment with the first nonbenzodiazepine antiseizure medication, however, was not uniformly distributed. The longest time to treatment occurred between 3 a.m. and 4 a.m., and the shortest time was between 3 p.m. and 4 p.m. “Although fewer refractory status epilepticus episodes occurred at night, the time to antiseizure medication administration was the longest [during that period]. Thus, nighttime refractory status epilepticus episodes may be at higher risk for delayed treatment,” said Ms. Clark. A limitation of this analysis is that it was influenced by outliers, she added.

The Pediatric Epilepsy Research Foundation and the Epilepsy Research Fund supported the study.

[email protected]

SOURCE: Clark J et al. AES 2018. Abstract 3.426.

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

Alcohol consumption and psychological distress are associated with possible REM sleep behavior disorder (RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.

The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”

To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.

In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.

Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.

In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.

When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.

One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.

“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
 

[email protected]

SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.

Alcohol consumption and psychological distress are associated with possible REM sleep behavior disorder (RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.

The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”

To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.

In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.

Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.

In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.

When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.

One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.

“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
 

[email protected]

SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.

Alcohol consumption and psychological distress are associated with possible REM sleep behavior disorder (RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.

The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”

To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.

In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.

Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.

In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.

When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.

One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.

“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
 

[email protected]

SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

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Apple Podcasts
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Spotify






 

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

Amazon
Apple Podcasts
Google Podcasts
Spotify






 

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

Amazon
Apple Podcasts
Google Podcasts
Spotify






 

Children in military families face unique challenges that other children do not face. Knee pathologies predict accelerated knee osteoarthritis, patients with a poor-prognosis cancer have a higher risk of suicide in the first year, and Nuedexta is mainly being prescribed for dementia and Parkinson’s.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Children in military families face unique challenges that other children do not face. Knee pathologies predict accelerated knee osteoarthritis, patients with a poor-prognosis cancer have a higher risk of suicide in the first year, and Nuedexta is mainly being prescribed for dementia and Parkinson’s.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Children in military families face unique challenges that other children do not face. Knee pathologies predict accelerated knee osteoarthritis, patients with a poor-prognosis cancer have a higher risk of suicide in the first year, and Nuedexta is mainly being prescribed for dementia and Parkinson’s.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify