Background: A unique patient with MELAS syndrome, who initially masqueraded as having acute encephalitis and was eventually diagnosed with MELAS syndrome harboring a mtDNA 14453G → A mutation, is described. Case presentation: A 74-year-old Japanese man was admitted to another hospital due to acute onset of cognitive impairment and psychosis. After 7 days he was transferred to our hospital with seizures and deteriorating psychosis. The results of primary ancillary tests that included EEG, CSF findings, and brain MRI supported the diagnosis of an acute encephalitis. HSV-DNA and antibodies against neuronal surface antigens in the CSF were all negative. With the assistance of the lactate peak on the brain lesions in the magnetic resonance spectroscopy image and genetic analysis of the biopsied muscle, he was eventually diagnosed with MELAS syndrome harboring mtDNA 14453G → A mutation in the ND6 gene. Conclusions: This case provides a caveat that MELAS syndrome can manifest in the symptoms and ancillary tests masquerading as an acute encephalitis caused by infection or autoimmunity. This is the first adult patient seen to harbor the mtDNA14453G → A with a unique onset, which broadens the phenotypic spectrum of MELAS syndrome associated with ND6 gene mutation.

We report the case of a 65-year-old man with COVID-19 (coronavirus disease-2019) post-infectious encephalitis who presented with delirium as an initial manifestation. He had severe COVID-19 pneumonia and recovered with dexamethasone and tocilizumab. One week after discharge, he developed abnormal behavior and delirium without fever and respiratory symptoms. Brain magnetic resonance imaging showed no abnormalities. Cerebrospinal fluid showed pleocytosis and elevated protein concentrations and was negative for severe acute respiratory syndrome-coronavirus-2 RNA. No anti-neuronal autoantibodies against intracellular and neuronal surface proteins were detected. The cerebrospinal fluid inflammatory changes compatible with post-infectious encephalitis, and the patient recovered with intravenous methylprednisolone and intravenous immunoglobulin therapy. Delirium could be an initial symptom of post-infectious encephalitis in older adults with COVID-19, and these patients may require immunosuppressive therapy.

ObjectiveTo establish the diagnostic biomarker of electroencephalogram (EEG) to distinguish between anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) and other types of autoimmune encephalitis (other AEs).MethodsWe reviewed the clinical records of 90 patients with acute encephalitis who were treated in our institution between January 2014 and October 2020. We enrolled the patients who fulfilled the diagnostic criteria for possible AE (pAE) defined by Graus et al. (pAE criteria) and then classified into definite NMDARE and other AEs. We investigated the main syndrome and analyzed all admission EEGs using EEG power value (PV). Statistical significance was tested using the Mann–Whitney U test or Fisher’s exact test.ResultsTwenty-five patients fulfilled the pAE criteria and were classified into 9 with definite NMDARE (median age: 21 years; 8 women) and 12 with other AEs (median age: 37.5 years; 6 women). Four were eventually excluded. Speech dysfunction (9/9 vs. 4/12, p = 0.005) and movement disorders (6/9 vs. 1/12, p = 0.016) were more frequent in NMDARE than in other AEs. The PV analyses revealed the novel quantitative EEG (qEEG) index, namely, fast slow ratio (FSR) (PV of total beta/PV of total theta + delta). The median FSR (0.139 vs. 0.029, p = 0.004) was higher for NMDARE than other AEs, and the receiver operating characteristic curve area of FSR was 0.86 (95% CI 0.70–1.00). A cutoff value of 0.047 yielded a specificity of 0.75 and a sensitivity of 1.00. Focusing on patients who did not meet the “probable NMDARE criteria” in Graus 2016 (proNMDARE criteria) (n = 10), the pretest probability of NMDAR antibody test was 0.30 (3/10), which increased in patients with an FSR greater than the cutoff (n = 5) to 0.60 (3/5).ConclusionsThe NMDARE group highlighted speech dysfunction and movement disorders, and a novel qEEG index FSR accurately distinguished the NMDARE patients from other AEs. The FSR is a promising diagnostic marker for NMDARE that indicates the positive results of NMDAR antibodies in patients with AE when combined with the proNMDARE criteria.

Rationale: Neurosyphilis presenting as limbic encephalitis (LE) is an important differential diagnosis of autoimmune LE (ALE) defined by Graus in 2016. However, data on the clinical differences and similarities between neurosyphilis presenting as LE and ALE are limited. Herein, we report neurosyphilis presenting as ALE that fulfilled the main items of the Graus ALE criteria. Moreover, a literature review of neurosyphilis presenting as LE was performed. Patient concerns: A 66-year-old Japanese man developed nonconvulsive status epilepticus. He presented with progressive personality change and working memory deficits within 3 months prior to admission. A hyperintense lesion localized in the bilateral medial temporal area was observed on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging. Cerebrospinal fluid analysis showed mild pleocytosis and the presence of oligoclonal band. However, in-house assays did not detect antineuronal antibodies. Electroencephalogram showed lateralized rhythmic delta activity in the right temporal area. The serum and cerebrospinal fluid serological and antigen tests for syphilis had positive results. Diagnosis: ALE was initially suspected based on the patient’s symptoms and ancillary test findings that fulfilled the Graus ALE criteria. However, based on the positive confirmatory test results for syphilis, a diagnosis of neurosyphilis was eventually made. Intervention: The patient received intravenous midazolam, oral levetiracetam, and lacosamide to control nonconvulsive status epilepticus. In addition, he was treated with intravenous benzylpenicillin at a dose of 24 million units/day for 14 days. Outcomes: The patient’s cognitive function relatively improved after antibiotic treatment. However, he presented with persistent mild working memory deficit, which was evaluated with the Wechsler Adult Intelligence Scale, 3rd edition. Therefore, on day 103 of hospitalization, he was transferred to another hospital for rehabilitation and long-term care due to limitations in performing activities of daily living. Lessons: The present case was diagnosed with neurosyphilis presenting as ALE, but meanwhile, in most case, neurosyphilis presenting as LE developed at a slower progressive rate, and it had a broader or restricted involvement on brain MRI than ALE based on the literature review. Therefore, an appropriate differential diagnosis of LE can be obtained by identifying clinical differences between the 2 conditions.

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