Citations

Abstract Hashimoto encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, has been defined by sub-acute onset encephalopathy, with elevated thyroid antibodies, and immunotherapy responsiveness, in the absence of specific neural autoantibodies. We aimed to retrospectively review 144 cases referred with suspected Hashimoto encephalopathy over a 13-year period, and to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients. One hundred and forty-four patients (all thyroid antibody positive) were included; 72% were women. Median age of symptom onset was 44.5 years (range, 10–87). After evaluation of Mayo Clinic, 39 patients (27%) were diagnosed with an autoimmune CNS disorder [autoimmune encephalopathy (36), dementia (2) or epilepsy (1)]. Three of those 39 patients had neural-IgGs detected (high glutamic acid decarboxylase-65, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-receptor and neural-restricted unclassified antibody), and 36 were seronegative. Diagnoses among the remaining 105 patients (73%) were functional neurological disorder (n = 20), neurodegenerative disorder (n = 18), subjective cognitive complaints (n = 14), chronic pain syndrome (n = 12), primary psychiatric (n = 11), sleep disorder (n = 10), genetic/developmental (n = 8), non-autoimmune seizure disorders (n = 2) and other (n = 10). More patients with autoimmune CNS disorders presented with sub-acute symptom onset (P < 0.001), seizures (P = 0.008), stroke-like episodes (P = 0.007), aphasia (P = 0.04) and ataxia (P = 0.02), and had a prior autoimmune history (P = 0.04). Abnormal brain MRI (P = 0.003), abnormal EEG (P = 0.007) and CSF inflammatory findings (P = 0.002) were also more frequent in the autoimmune CNS patients. Patients with an alternative diagnosis had more depressive symptoms (P = 0.008), anxiety (P = 0.003) and chronic pain (P = 0.002). Thyoperoxidase antibody titre was not different between the groups (median, 312.7 versus 259.4 IU/ml; P = 0.44; normal range, <9 IU/ml). None of the non-autoimmune group and all but three of the CNS autoimmune group (two with insidious dementia presentation, one with seizures only) fulfilled the autoimmune encephalopathy criteria proposed by Graus et al. (A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15: 391–404.) (sensitivity, 92%; specificity, 100%). Among patients who received an immunotherapy trial at our institution and had objective post-treatment evaluations, the 16 responders with autoimmune CNS disorders more frequently had inflammatory CSF, compared to 12 non-responders, all eventually given an alternative diagnosis (P = 0.02). In total, 73% of the patients referred with suspected Hashimoto encephalopathy had an alternative non-immune-mediated diagnosis, and more than half had no evidence of a primary neurological disorder. Thyroid antibody prevalence is high in the general population, and does not support a diagnosis of autoimmune encephalopathy in the absence of objective neurological and CNS-specific immunological abnormalities. Thyroid antibody testing is of little value in the contemporary evaluation and diagnosis of autoimmune encephalopathies.

Background: Myelitis accompanied by a negative spinal cord MRI may lead to diagnostic uncertainty. Objective and Methods: We retrospectively investigated the frequency of negative spinal cord MRI (performed <6 weeks from onset) in Mayo Clinic patients with myelin oligodendrocyte glycoprotein (MOG)-IgG-associated myelitis (2000–2019). Results: The initial spinal cord MRI was negative in 7/73 (10%) patients, despite severe acute disability (median EDSS, 7 (range, 4.5–8)); myelitis symptoms/signs were frequent (paraparesis, neurogenic bladder, sensory level, Lhermitte’s phenomenon). Myelitis lesions became overt at follow-up MRI in three patients. Conclusions: A negative spinal cord MRI should not dissuade from MOG-IgG testing in patients with acute/subacute myelitis.

ObjectiveDrug‐resistant seizures are common in patients with leucine‐rich, glioma‐inactivated 1 (LGI1)‐IgG associated and contactin‐associated protein‐like 2 (CASPR2)‐IgG associated encephalitis. We performed the first randomized double‐blind placebo‐controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency.MethodsOur enrollment goal was 30 LGI1/CASPR2‐IgG–seropositive adult patients with ≥2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume‐matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5 weeks.ResultsAfter enrollment of 17 patients (LGI1‐IgG, 14; CASPR2‐IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p = 0.044, odds ratio = 10.5, 95% confidence interval = 1.1–98.9). For the LGI1‐IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1‐IgG–seropositive patients receiving IVIG, but none receiving placebo, were seizure‐free at the end of the blinded phase. Four of the 6 patients entering the open‐label IVIG arm reported ≥50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2‐IgG1–4 subclasses.InterpretationSuperiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1‐IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313–323