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Diagnosing & Treating Neuromyelitis Optica Spectrum Disorder
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
