Citations

ABSTRACTCavin‐4 was identified as a potential autoantigen for immune‐mediated rippling muscle disease (iRMD). To validate this, we developed and tested various immunoassays, including a cell‐based assay (CBA), cavin‐4 recombinant protein ELISA, and multi‐peptide ELISA. Among 19 iRMD patients, all exhibited muscle rippling, and 13 had percussion‐induced mounding. All immunoassays demonstrated clinical and analytical specificities greater than 95%. The protein ELISA had the highest sensitivity (94.7%) and specificity (99.9%), outperforming CBA (sensitivity 89.5%, specificity 99.6%) and the multi‐peptide ELISA (sensitivity 79.0%, specificity 97.2%). Our results suggest that the cavin‐4 protein ELISA is a promising tool for high‐throughput clinical testing in iRMD.

AbstractCases of myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) co‐occurring with neoplasms have been reported. In this international, retrospective cohort study in South Korea and the USA, 16 of 445 (3.6%) patients with MOGAD had concurrent neoplasm within 2 years of MOGAD onset, resulting in a standardized incidence ratio for neoplasm of 3.10 (95% confidence interval [CI], 1.77–4.81; P < 0.001) when compared to the age‐ and country‐adjusted incidence of neoplasm in the general population. However, none of the nine tumor tissues obtained demonstrated MOG immunostaining. The slightly increased frequency without immunohistopathological evidence suggest with true paraneoplastic MOGAD is extremely rare.

Abstract Objective To assess the real‐world performance of a live (LCBA) versus a fixed (FCBA) cell‐based assay for the detection of serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG‐IgG) and aquaporin‐4 (AQP4‐IgG). Methods This was a retrospective study of patients evaluated at a single tertiary academic referral center, with serum testing performed clinically for AQP4‐IgG and/or MOG‐IgG by FCBA and LCBA on the same day. Additionally, frozen banked sera from the same day for patients tested only by one assay were retrieved and tested by the other assay. FCBA was performed by the Johns Hopkins Immunology Laboratory using Euroimmun kits with detection by indirect immunofluorescence (FCBA‐IF), whereas LCBA was performed by the Mayo Clinic Neuroimmunology Laboratory with detection by flow cytometry (LCBA‐FACS). Results Of 594 specimens with paired MOG‐IgG testing, 500 were negative by both assays, 33 were positive by both assays, 56 were positive exclusively by LCBA‐FACS, and 5 were only positive by FCBA‐IF. Overall, MOG‐IgG LCBA‐FACS exhibited 95.1% sensitivity and 97.7% specificity, whereas MOG‐IgG FCBA‐IF had 45.7% sensitivity and 99.8% specificity. Of 577 specimens with paired AQP4‐IgG testing, 503 were negative by both assays, 51 were positive by both assays, 21 were positive exclusively by LCBA‐FACS, and 2 were only positive by FCBA‐IF. Overall, AQP4‐IgG LCBA‐FACS exhibited 97.3% sensitivity and 100% specificity, whereas AQP4‐IgG FCBA‐IF had 71.6% sensitivity and 100% specificity. Interpretation LCBA‐FACS for both MOG‐IgG and AQP4‐IgG had markedly better sensitivity than FCBA‐IF, with similar specificity. The use of FCBA‐IF may result in underrecognition of both MOG antibody‐associated disease (MOGAD) and AQP4‐IgG seropositive neuromyelitis optica spectrum disorder (NMOSD).

AbstractDefining the CSF cytokine/chemokine and injury biomarker signature of glial fibrillary acidic protein (GFAP) autoimmunity can inform immunopathogenesis. CSF GFAP‐IgG‐positive samples (N = 98) were tested for 17 cytokines/chemokines, neurofilament light chain (NfL), and GFAP (ELLA, Bio‐Techne). Controls included non‐inflammatory (N = 42), AQP4‐IgG‐positive (N = 83), CNS infections (N = 13), and neurosarcoidosis (N = 32). IL5, IL6, IL10, IL8/CXCL8, CXCL9, CXCL10, CXCL13, BAFF, GM‐CSF, IFN‐gamma, and TNF‐alpha concentrations were higher compared to non‐inflammatory controls (P < 0.01). GFAP concentrations were similar to those of AQP4‐IgG‐positive patients; NfL was higher (P < 0.001) and correlated with MRI changes and outcomes. CSF cytokine/chemokine findings in GFAP autoimmunity correlate with histopathology; GFAP and NfL hold promise as disease biomarkers.

Background Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited. Methods This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed. Results Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)). Conclusion While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.

AbstractObjectiveWe describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis.MethodsMedical records of neural‐IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed.ResultsNinety‐eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months‐85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL‐11 (26 patients), GAD65 (high titer, 12), ANNA‐1 (anti‐Hu, 8), ANNA‐2 (anti‐Ri, 8), Ma2 (7), IgLON‐5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA‐1 (anti‐Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA‐R (2), AGNA‐1 (SOX‐1, 1), ANNA‐3 (DACH1, 1), amphiphysin (1), CRMP‐5 (1), ITPR‐1 (1), PCA‐Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra‐testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow‐up was 3 (range, 0–6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan–Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed.InterpretationAutoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF‐IgG index associate with poor outcome.