Citations

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.

ImportanceAutoimmune encephalitis misdiagnosis can lead to harm.ObjectiveTo determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis.Design, Setting, and ParticipantsThis retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), Washington University in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.Main Outcomes and MeasuresData were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions.ResultsA total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (&amp;gt;3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).Conclusions and RelevanceWhen evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Cerebral cortical encephalitis (CCE) is a recently described myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) phenotype. In this observational retrospective study, we characterized 19 CCE patients (6.7% of our MOGAD cohort). Headache (n = 15, 79%), seizures (n = 13, 68%), and encephalopathy (n = 12, 63%) were frequent. Magnetic resonance imaging revealed unilateral (n = 12, 63%) or bilateral (n = 7, 37%) cortical T2 hyperintensity and leptomeningeal enhancement (n = 17, 89%). N‐Methyl‐D‐aspartate receptor autoantibodies coexisted in 2 of 15 tested (13%). CCE pathology (n = 2) showed extensive subpial cortical demyelination (n = 2), microglial reactivity (n = 2), and inflammatory infiltrates (perivascular, n = 1; meningeal, n = 1). Most received high‐dose steroids (n = 17, 89%), and all improved, but 3 had CCE relapses. This study highlights the CCE spectrum and provides insight into its pathogenesis. ANN NEUROL 2023;93:297–302