Coexistence of multiple sclerosis and spinocerebellar ataxia type-8.

Cerebellar dysfunction is likely to cause severe and treatment-resistant disability in multiple sclerosis (MS). Certain spinocerebellar ataxia (SCA)-related alleles can increase MS susceptibility, and channel polymorphisms can impact disability measures. Following an index patient with the coexistence of MS and SCA Type-8 (SCA8) in the MS clinic, an institutional engine search for MS and hereditary ataxia coexistence was conducted but did not reveal any other cases. This extremely rare coexistence of MS and SCA8 in our index patient may be incidental; however, a yet-to-be-identified contribution of coexistent hereditary ataxia(s) to the susceptibility of a prominent progressive ataxia MS phenotype cannot be ruled out.

Spinal cord and brain corticospinal tract lesions are associated with motor progression in tumefactive multiple sclerosis.

BACKGROUND: Spinal cord lesions have been associated with progressive disease in individuals with typical relapsing remitting MS (RRMS). OBJECTIVE: In the current study, we aimed to determine if progressive disease is associated with spinal cord lesions in those with tumefactive multiple sclerosis (MS). METHODS: Retrospective chart review of individuals presenting to Mayo Clinic with tumefactive MS with spinal cord MRIs available (n=159). Clinical data were extracted by chart review. Brain and spinal cord MRIs were reviewed to characterize the tumefactive demyelinating lesion(s) and assess the burden of spinal cord disease. RESULTS: A total of 69 (43%) had spinal cord lesions. Progressive demyelinating disease was documented in 13 (8%); the majority (11/13) with secondary progressive disease. The method of progression was myelopathic in 8/13 (62%), cognitive in 3/13 (23%), motor from a supratentorial lesion in 2/13 (16%). EDSS at last follow-up was higher in those with progression than those without (median 6.0 (2.0-10.0) vs. 2.5 (0-10.0), p = < 0.001). Progressive demyelinating disease occurred in a minority. CONCLUSIONS: Patients with progression typically experienced progressive motor impairment, and this occurred exclusively in individuals with lesions in the corticospinal tracts of the brain and/or the spinal cord.

Progressive motor impairment from "critical" demyelinating lesions of the cervicomedullary junction.

BACKGROUND: Progressive motor impairment anatomically associated with a "critical" lesion has been described in primary demyelinating disease. Most "critical" lesions occur within the spinal cord. OBJECTIVE: To describe the clinical and radiological features of "critical" lesions of the cervicomedullary junction (CMJ). METHODS: Observational study on people presenting with a CMJ lesion associated with primary demyelinating disease-related progressive motor impairment. Clinical data were extracted by chart review. Brain and spinal cord magnetic resonance images were reviewed to characterize the CMJ lesion and determine additional demyelination burden. RESULTS: Forty-one people were included: 29 (71%) had progression from onset and 12 (29%) had a relapse onset (secondary progressive) course. Most had progressive hemiparesis (21 (51%)) or progressive quadriparesis (15 (37%)) with a median Expanded Disability Status Scale (EDSS) of 5.5 (2.0-8.5) at last follow-up. No "critical" CMJ lesion enhanced; most were bilateral (25 (61%)). Brain magnetic resonance images were otherwise normal in 16 (39%) or with a restricted demyelination burden in 15 (37%). Cervical and thoracic cord MRIs were without additional lesions in 25 (61%) and 22/37 (59%), respectively. CONCLUSION: CMJ "critical" lesions can correlate with progressive motor impairment even with few or no additional magnetic resonance imaging (MRI) lesions. Lesion location is an important determinant of progressive motor impairment in demyelinating disease.

Diagnosis of coexistent neurodegenerative dementias in multiple sclerosis.

Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. The use of biomarkers such as PET and CSF proteins may facilitate this distinction. The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aß1-42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P = 0.006), had longer disease duration [median (range) 20 years (3-59) versus 9 (1-32), P = 0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1-38) versus 31 (9-34) P = 0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most biomarker-cohort patients had informative results evaluating coexistent neurogenerative disease. Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment.

Cerebrospinal fluid evaluation in patients with progressive motor impairment due to critical central nervous system demyelinating lesions.

BACKGROUND: Elevated intrathecal immunoglobulin G (IgG; oligoclonal bands (OCBs)) or IgG in people with progressive motor impairment due to "critical" demyelinating lesions are of uncertain significance. OBJECTIVE: Compare clinical/radiological features of people with "critical" demyelinating lesion-induced progressive motor impairment with/without elevated intrathecal IgG synthesis. METHODS: A total of 133 people with progressive motor impairment attributable to "critical" demyelinating lesions (corticospinal tract location, consistent with the progressive motor deficit) were compared regarding clinical and radiological presentation with and without ≥2 unique cerebrospinal fluid (CSF) OCB and/or IgG index ≥0.85. RESULTS: Ninety-eight (74%) had CSF-elevated OCB and/or IgG index, higher with increased magnetic resonance imaging-lesion burden. No differences were found with/without CSF abnormalities in sex (46 of 98 female (47%) vs. 22 of 35 (63%), p = 0.11), onset-age (median 49 vs. 50 years, p = 0.5), progression from onset (62 of 98 (63%) vs. 25 of 35 (71%)), progression post-relapse (36 of 98 (37%) vs. 10 of 35 (29%), p = 0.4), and duration between demyelinating disease onset and CSF examination (30 (0-359) vs. 48 (0-323) months p = 0.7). "Critical" lesions were radiologically similar, most commonly cervical spine located (72 of 98 (74%) vs. 19 of 35 (54%), p = 0.18) both with/without CSF abnormalities. CONCLUSIONS: People with "critical" demyelinating lesion-induced progressive motor impairment typically have elevated intrathecal IgG (OCB and/or IgG) and similar clinical and radiological presentation regardless of CSF findings, therefore representing valid presentations of progressive demyelinating disease.

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders.

BACKGROUND AND OBJECTIVE: There are few studies comparing lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2 lesion evolution in myelin oligodendrocyte glycoprotein immunoglobulin G (IgG)-associated disorder (MOGAD), aquaporin 4 IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS). METHODS: In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and (1) brain or myelitis attack; (2) available attack MRI within 6 weeks; and (3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2 lesion for each patient (index lesion). MRIs were then independently reviewed by 2 neuroradiologists blinded to diagnosis to determine resolution of T2 lesions by consensus. The index T2 lesion area was manually outlined acutely and at follow-up to assess variation in size. RESULTS: We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]), and MS (37 [16-61]) (p < 0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2 lesion was more frequent in MOGAD (brain, 13/18 [72%]; spine, 22/28 [79%]) than AQP4-IgG-NMOSD (brain, 3/21 [14%]; spine, 0/34 [0%]) and MS (brain, 7/42 [17%]; spine, 0/29 [0%]) (p < 0.001). Resolution of all T2 lesions occurred most often in MOGAD (brain, 7/18 [39%]; spine, 22/28 [79%]) than AQP4-IgG-NMOSD (brain, 2/21 [10%]; spine, 0/34 [0%]) and MS (brain, 2/42 [5%]; spine, 0/29 [0%]) (p < 0.01). There was a larger median (range) reduction in T2 lesion area in mm2 on follow-up axial brain MRI with MOGAD (213 [55-873]) than AQP4-IgG-NMOSD (104 [0.7-597]) (p = 0.02) and MS (36 [0-506]) (p < 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262 [0-888]) and AQP4-IgG-NMOSD (309 [0-1885]) were similar (p = 0.4) and greater than in MS (23 [0-152]) (p < 0.001). DISCUSSION: The MRI T2 lesions in MOGAD resolve completely more often than in AQP4-IgG-NMOSD and MS. This has implications for diagnosis, monitoring disease activity, and clinical trial design, while also providing insight into pathogenesis of CNS demyelinating diseases.

Onset of progressive motor impairment in patients with critical central nervous system demyelinating lesions.

OBJECTIVE: To compare progressive motor impairment onset attributable to a "critical" central nervous system (CNS) demyelinating lesion in patients with highly restricted versus unlimited magnetic resonance imaging (MRI) lesion burden. METHODS: We identified 135 patients with progressive motor impairment for ⩾1 year attributable to a "critical" demyelinating lesion with: MRI burden of 1 lesion ("progressive solitary sclerosis"), 2-5 lesions ("progressive paucisclerosis"), or unrestricted (>5) lesions and "progressive unilateral hemiparesis." Neuroradiology review of brain and spinal cord MRI documented unequivocally demyelinating lesions. RESULTS: A total of 33 (24.4%) patients had progressive solitary sclerosis; 56 (41.5%) patients had progressive paucisclerosis; and 46 (34.1%) patients had progressive unilateral hemiparesis. Median age at onset of progressive motor impairment was younger in progressive solitary sclerosis (49 years; range 24-73) and progressive paucisclerosis (50 years; range 30-64) than in progressive unilateral hemiparesis (54 years; range 39-77; p = 0.02 and p = 0.003, respectively). Within progressive unilateral hemiparesis, motor-progression onset was similar between those with 4-10, 11-20, or >20 brain lesions (55, 54, 53 years of age, respectively; p = 0.44). CONCLUSION: Motor-progression age is similar, but paradoxically earlier, in cohorts with highly restricted CNS lesion burden than in those with unrestricted lesion burden with progressive unilateral hemiparetic MS. The "critical" demyelinating lesion rather than total brain MRI lesion burden is the major contributor to motor-progression onset in these cohorts.

Critical spinal cord lesions associate with secondary progressive motor impairment in long-standing MS: A population-based case-control study.

BACKGROUND: Progressive motor impairment anatomically attributable to prominent, focally atrophic lateral column spinal cord lesions ("critical lesions") can be seen in multiple sclerosis (MS), for example, progressive hemiparetic MS. OBJECTIVE: The aim of this study was to investigate whether similar spinal cord lesions are more frequent in long-standing MS patients with secondary progressive motor impairment (secondary progressive MS (SPMS)) versus those maintaining a relapsing-remitting course (relapsing-remitting MS (RRMS)). METHODS: We retrospectively identified Olmsted County (MN, USA) residents on 31 December 2011 with (1) RRMS or SPMS for ⩾25 years, and (2) available brain and spine magnetic resonance imaging (MRI). A blinded neuroradiologist determined demyelinating lesion burden and presence of potential critical lesions (prominent focally atrophic spinal cord lateral column lesions). RESULTS: In total, 32 patients were included: RRMS, 18; SPMS, 14. Median (range) disease duration (34 (27-53) vs. 39 (29-47) years) and relapse number (4 (1-10) vs. 3 (1-15)) were similar. In comparison to RRMS, SPMS patients more commonly showed potential critical spinal cord lesions (8/18 (44%) vs. 14/14 (100%)), higher spinal cord (median (range) 4 (1-7) vs. 7.5 (3-12)), and brain infratentorial (median (range) 1 (0-12) vs. 2.5 (1-13)) lesion number; p < 0.05. By multivariate analysis, only the presence of potential critical lesions independently associated with motor progression (p = 0.02). CONCLUSION: Critical spinal cord lesions may be important contributors to motor progression in MS.

Inflammatory activity following motor progression due to critical CNS demyelinating lesions.

BACKGROUND: New inflammatory activity is of unclear frequency and clinical significance in progressive multiple sclerosis (MS); it is uncertain in patient cohorts with motor progression due to critical demyelinating lesions. OBJECTIVES: The aim of this study is to determine the likelihood of central nervous system (CNS) inflammatory activity, assessed by new clinical relapses or active magnetic resonance imaging (MRI) lesions, following onset of motor progression due to critical demyelinating lesions. METHODS: Patients with progressive upper motor neuron impairment for ⩾1 year attributable to critical demyelinating lesions with single CNS lesion (progressive solitary sclerosis (PSS)), 2 to 5 total CNS demyelinating lesions (progressive "pauci-sclerosis" (PPS)), or >5 CNS demyelinating lesions and progressive exclusively unilateral monoparesis or hemiparesis (PUHMS) were identified. Clinical data were reviewed for acute MS relapses, and subsequent MRI was reviewed for active T1-gadolinium-enhancing or T2-demyelinating lesions. RESULTS: None of the 91 patients (22 PSS, 40 PPS, 29 PUHMS) identified experienced clinical relapses over a median clinical follow-up of 93 months (range: 12-518 months). Nine patients (10%) developed active lesions over median 84 months radiologic follow-up (range: 12-518 months). Active lesions occurred in 24% PUHMS, 5% PSS, and 3% PPS cohorts. CONCLUSION: New inflammatory activity, defined by active lesions and clinical relapses following motor progression in patients with critical demyelinating lesions, is low. Disease-modifying therapies that reduce demyelinating relapses and active MRI lesions are of uncertain benefit in these cohorts.

Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events.

Importance: Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood. Objective: To evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events. Design, Setting, and Participants: A nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex. Exposures: TNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure. Main Outcomes and Measures: The main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis). Results: A total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005). Conclusions and Relevance: This study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.

Spinal cord infarction in a patient with multiple sclerosis.

We describe a 49 year old woman with relapsing-remitting multiple sclerosis (MS) with a suspected severe recurrent attack of myelitis that was ultimately diagnosed as a spinal cord infarction (SCI). This case of SCI in a patient with an established diagnosis of MS highlights the clinical, laboratory, and radiographic characteristics that help distinguish SCI from inflammatory myelitis due to MS.

Unilateral motor progression in MS: Association with a critical corticospinal tract lesion.

OBJECTIVE: Progressive motor impairment anatomically attributable to a single critical demyelinating lesion on eloquent corticospinal tract locations occurs in progressive solitary sclerosis and in some patients with multiple sclerosis (MS) with highly restricted CNS lesion burden (2-5 lesions). We determined whether a similar critical lesion is found in patients with MS with unilateral motor progression and unlimited lesion burden. METHODS: In this observational study, we retrospectively identified Mayo Clinic patients (January 1, 1996-December 31, 2017) with an MS diagnosis (2017 McDonald criteria), ≥1 year of exclusively unilateral motor progression, and >5 demyelinating lesions on MRI. A blinded neuroradiologist identified a single critical lesion (last available MRI) based on prominent size, atrophy, and eloquent corticospinal tract location (spinal cord lateral columns, medullary pyramids, cerebral peduncles, internal capsules). We then determined whether the motor impairment was anatomically attributable to the identified lesion. RESULTS: Thirty-eight patients with MS were included: 20 (53%) with primary progressive MS and 18 (47%) with secondary progressive MS. Median age at progression onset was 54 (range 39-73) years. Median Expanded Disability Status Scale score was 5 (range 2.5-7.5) at the last follow-up (median 132.5 months from symptom onset, range 23-390 months). A single critical lesion was identified in 25 of 38 cases (66%): 19 in the cervical cord and 6 in the thoracic cord. In the remaining patients, >1 potential critical lesions were present. The overall probability to detect demyelinating lesions was higher along the corticospinal tract where the motor deficit localized (38 of 38 [100%]) than on the contralateral side (15 of 38 [39%]) (p < 0.0001). CONCLUSIONS: In patients with MS with unilateral motor progression, the motor deficit may be attributable to a single critical corticospinal tract lesion.

Aquaporin-4 and MOG autoantibody discovery in idiopathic transverse myelitis epidemiology.

OBJECTIVE: Diagnostic criteria from 2002 classify transverse myelitis (TM) as idiopathic or disease associated but predate the discovery of aquaporin-4 (AQP4)-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which associate with TM. Prior incidence estimates of idiopathic TM (ITM) range from 1 to 6.2 per 1 million. We sought to determine whether the population-based incidence and prevalence of ITM were reduced by testing patients with ITM for AQP4/MOG-IgG and reclassifying seropositive cases as having disease-associated TM. METHODS: For this observational study, we retrospectively identified all cases of incident (January 1, 2003-December 31, 2016) and prevalent (December 31, 2016) ITM in Olmsted County (85% white) by using the Rochester Epidemiology Project medical records linkage system. ITM was defined by the 2002 Transverse MyelitisConsortium Working Group diagnostic criteria. Available sera were tested for AQP4-IgG and MOG-IgG. RESULTS: Twenty-four patients (incident 22, prevalent 17) initially met 2002 ITM criteria (longitudinally extensive TM [LETM] 6). Sera were tested for AQP4-IgG in 22 of 24 (92%) and MOG-IgG in 21 of 24 (88%). Three seropositive cases (AQP4-IgG 2, MOG-IgG 1) were identified and reclassified as having disease-associated TM, accounting for 14% of total incident and 12% of total prevalent cases. AQP4-IgG and MOG-IgG seropositive cases represented 50% (3 of 6) of idiopathic LETM. After reclassification of seropositive patients, the final ITM incidence was 8.6 per 1,000,000 and prevalence was 7.9 per 100,000. Three cases of ITM (14%) subsequently fulfilled multiple sclerosis criteria within the study period. CONCLUSIONS: The availability of AQP4-IgG and MOG-IgG modestly reduced ITM incidence and prevalence, which remained higher than previously reported in this predominantly white population. Incorporation of these biomarkers into future revisions of TM diagnostic criteria should be considered.

Late-onset Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes Presenting With Auditory Agnosia.

INTRODUCTION: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a multisystemic mitochondrial disorder that usually presents in childhood. Patients can have a wide array of neurological symptoms when presenting with stroke-like episodes, and imaging characteristics during the episodes can overlap with different neurological disorders. CASE REPORT: A 61-year-old woman presented with communication difficulties consistent with auditory agnosia and was found to have bitemporal abnormalities on imaging that first raised the concern for herpes simplex virus encephalitis. Further work-up, in conjunction with the patient's past medical and family history, suggested a mitochondrial disorder. Mitochondrial full genome analysis revealed m.3243A>G variant in the MT-TL1 gene, with 6% heteroplasmy in blood leading to a diagnosis of MELAS. CONCLUSIONS: MELAS is a disorder with clinical variability. Neuroimaging studies during stroke-like episodes in MELAS can provide significant clues to the underlying disorder. Although patients typically present in childhood, the first stroke-like episode can occur later in life in some patients, potentially related to a lower heteroplasmy level.

Polyneuropathies and chronic inflammatory demyelinating polyradiculoneuropathy in multiple sclerosis.

BACKGROUND: Polyneuropathies co-occurring with multiple sclerosis (MS) may be underdiagnosed while causing additional disability burden. OBJECTIVE: To determine polyneuropathy presence and type in MS and compare MS with chronic inflammatory demyelinating polyradiculoneuropathy (MS-CIDP) versus MS with other non-inflammatory polyneuropathies. METHODS: Retrospective chart review of Mayo Clinic cases diagnosed with MS and polyneuropathy. Serum from MS-CIDP for pan-IgG autoantibodies to neurofascin-155 were tested when available. RESULTS: From 1980-2013, 133 co-existing MS/ polyneuropathy cases were identified. Twenty-eight MS patients had inflammatory neuropathy (11 CIDP, 5 plexopathy, 2 vasculitis, 4 monoclonal gammopathy-associated, 6 other), 15 inherited neuropathy (8 axonal, 7 demyelinating), 32 diabetic sensorimotor polyneuropathy, and 58 other. 109 had neuropathy beginning simultaneous to or after MS diagnosis (82%). Compared to MS cases with other polyneuropathy subtypes, MS-CIDP cases had absent or reduced ankle reflexes (100 vs. 70%, p = 0.04), earlier age of neuropathy recognition (52 vs. 58 years, p = 0.048), worse impairment (NIS 27 vs. 22 points, p < 0.03), and more acquired demyelinating electrophysiology features (46% vs. 9%, p < 0.003). Of MS-CIDP cases with available serum, 1-in-3 had IgG4 autoantibodies to neurofascin-155. CONCLUSION: (1) Polyneuropathies occurring in MS contribute to neurological disability. (2) Diagnosing polyneuropathies in people with MS is challenging and, likely, under-diagnosed. Recognition is important as some polyneuropathies (e.g., CIDP) are treatable. (3) The probable over-representation of inflammatory neuropathy (especially CIDP) in MS suggests a shared dysimmune pathogenesis, supported by autoantibodies to neurofascin-155.

Advanced imaging findings in progressive solitary sclerosis: a single lesion or a global disease?

BACKGROUND: Progressive solitary sclerosis is a unifocal demyelinating disease recently proposed as a possible multiple sclerosis variant. OBJECTIVE: To compare myelin content and brain metabolite ratio qualitatively in the normal-appearing white matter of progressive solitary sclerosis cases compared to multiple sclerosis and healthy control participants. METHODS: Case report. RESULTS: Progressive solitary sclerosis cases showed abnormal myelin in normal-appearing white matter tracts and global normal-appearing white matter as well as lower N-acetyl-aspartate to total creatine ratio compared to multiple sclerosis and healthy control groups. CONCLUSION: Despite a single demyelinating lesion along the corticospinal tract in progressive solitary sclerosis, we showed evidence of more extensive abnormality within the normal-appearing white matter.

Clinical, Radiologic, and Prognostic Features of Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Autoantibody.

Importance: Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective: To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4-IgG (AQP4-IgG) and multiple sclerosis (MS). Design, Setting, and Participants: We retrospectively identified 199 MOG-IgG-positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through our neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. We excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison. Main Outcomes and Measures: Outcome variables included modified Rankin score and need for gait aid. A neuroradiologist analyzed spine magnetic resonance imaging of patients with MOG-IgG and control patients blinded to diagnosis. Results: Of 54 included patients with MOG-IgG myelitis, the median age was 25 years (range, 3-73 years) and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid-elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up (median, 24 months; range, 2-120 months), 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis. Magnetic resonance imaging features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%]; P = .52) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG. Conclusions and Relevance: Myelitis is an early manifestation of MOG-IgG-related disease and may have a clinical phenotype of acute flaccid myelitis. We identified a variety of clinical and magnetic resonance imaging features that may help clinicians identify those at risk in whom MOG-IgG should be tested.