Sechi, Elia

Background: Acute disseminated encephalomyelitis (ADEM) is a demyelinating syndrome observed in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) but there are limited data on application of this definition to its cerebral attacks or in adults with this disease. Methods: We analyzed patients from the Mayo Clinic MOGAD cohort ( n = 263) with cerebral attacks. We assessed whether children (<18 years-old) and adults (⩾18 years-old) fulfilled the 2013 ADEM definition. Results: We identified 89 patients (children, 34; adults, 55) and 55/89 (62%) were of female sex. Acute magnetic resonance imaging (MRI) abnormalities included: poorly demarcated T2 lesions (white matter, 85 (96%); deep gray matter, 41 (46%); T1-hypointense lesions (42 (47%)). Forty-two patients did not fulfill the ADEM definition due to: monofocal syndrome, 9; or no encephalopathy, 33. The remaining 47 patients (53%: children, 27/34 (79%); adults, 20/55 (36%)) fulfilled the ADEM definition, and 14 had preceding attacks, and 34 had subsequent attacks relative to ADEM episode. The features in children and adults with ADEM were broadly comparable. Conclusion: Applying the ADEM definition to MOGAD cerebral attacks highlighted that an update of the 2013 ADEM definition would be beneficial and could explicitly state its application to both adults and children and allow it to be applied to attacks at any time during the disease course.

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) have both overlapping and distinct MRI lesion features, which vary with imaging timing. This study identified distinguishing MRI characteristics using paired MRIs at clinical attack and remission. Methods We retrospectively identified Mayo Clinic patients with MOGAD and MS that: (1) fulfilled respective diagnostic criteria; (2) had paired attack (≤30 days) and remission MRI scans (≥12 months) without interval attacks. MRIs were compared between groups for key features. Results We included 43 patients with MOGAD (median age 31 years (range, 3–67); 63% female) and 49 patients with MS (median age 39 years (range, 17–65); 65% female). Resolution of at least one T2-lesion differentiated MOGAD from MS (sensitivity, (95% CI 77% to 100%), specificity, (95% CI 86% to 99%); Youden’s index (YI)=0.90). Resolution of at least two T2-lesions indicated MOGAD (sensitivity 62% (95% CI 41% to 79%); specificity, 100% (95% CI 94% to 100%); YI=0.62). MOGAD patients were more likely to have normal MRI scans at follow-up compared with MS (brain 14/44 (32%) vs 0/60 (0%), p<0.001; spine 21/27 (78%) vs 7/36 (19%), p<0.001). In addition, the presence of T1-hypointense, ovoid periventricular T2, and enhancing lesions were more common in MS versus MOGAD at attack and remission and in the spine, longitudinally extensive T2 lesions were more common in MOGAD attacks (8/27 (30%)). Conclusion Paired MRI at attack and remission revealed distinctive characteristics of MOGAD and MS, with greater diagnostic value at remission driven by the discriminating power of T2-lesion resolution. In MOGAD patients with initial parenchymal involvement, a 1-year follow-up MRI may aid diagnosis and serve as a new baseline.

Background: Rapidly reversible weakness with neck flexion (McArdle sign) is common in patients with multiple sclerosis (MS). The pathophysiology is unknown. Objective: To evaluate changes in central motor conduction time (CMCT) in patients with and without McArdle sign. Methods: We measured McArdle sign with a torque cell and CMCT with neck flexed and extended in patients with MS, other causes of myelopathy, and healthy controls. Results: CMCT was prolonged with neck flexion disproportionately in those with MS-associated myelopathy (MSAM) with prominent McArdle sign compared to MS patients with lesser degrees of McArdle sign, and to controls. Conclusion: McArdle sign may result from stretch-induced slowing of conduction due to demyelination.

Abstract Background Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin‐4‐IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein‐IgG associated disease (MOGAD) represent major and well‐defined differential diagnoses, non‐demyelinating NMOSD mimics remain poorly characterized. Methods We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non‐demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified. Results A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1–78) years. Fifty‐six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune‐mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin‐4‐IgG positivity was detected in five patients by enzyme‐linked immunosorbent assay ( n = 2), cell‐based assay ( n = 2: serum, 1; CSF, 1), and non‐specified assay ( n = 1). Conclusions The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin‐4‐IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.

Background: Magnetic resonance imaging (MRI) T2-lesions resolve more often in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) than aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and multiple sclerosis (MS) in adults but few studies analyzed children. Objective: The main objective of this study is to investigate MRI T2-lesion evolution in pediatric MOGAD, AQP4 + NMOSD, and MS. Methods: Inclusion criteria were as follows: (1) first clinical attack; (2) abnormal MRI (⩽6 weeks); (3) follow-up MRI beyond 6 months without relapses in that region; and (4) age < 18 years. An index T2-lesion (symptomatic/largest) was identified, and T2-lesion resolution or persistence on follow-up MRI was determined. Results: We included 56 patients (MOGAD, 21; AQP4 + NMOSD, 8; MS, 27) with 69 attacks. Index T2-lesion resolution was more frequent in MOGAD (brain 9 of 15 [60%]; spine 8 of 12 [67%]) than AQP4 + NMOSD (brain 1 of 4 [25%]; spine 0 of 7 [0%]) and MS (brain 0 of 18 [0%]; spine 1 of 13 [8%]), p < 0.01. Resolution of all T2-lesions occurred more often in MOGAD (brain 6 of 15 [40%]; spine 7 of 12 [58%]) than AQP4 + NMOSD (brain 1 of 4 [25%]; spine 0 of 7 [0%]), and MS (brain 0 of 18 [0%]; spine 1 of 13 [8%]), p < 0.01. Reductions in median index T2-lesion area were greater in MOGAD (brain, 305 mm; spine, 23 mm) than MS (brain, 42 mm [ p<0.001]; spine, 10 mm [ p<0.001]) without differing from AQP4 + NMOSD (brain, 133 mm [ p=0.42]; spine, 19.5 mm [ p=0.69]). Conclusion: In children, MRI T2-lesions resolved more often in MOGAD than AQP4 + NMOSD and MS which is similar to adults suggesting these differences are related to pathogenesis rather than age.