The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-Daspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.
ObjectiveWe present a rare case with anti-Homer-3 antibodies positive encephalitis in the youngest patient ever identified and reviewed the literature.Case ReportA 10-year-old, Chinese boy came for evaluation of a 2-week history of cognitive impairment, irritability, dysarthria, and cautious gait. The neurological examination was consistent with the pan-cerebellar syndrome and encephalopathy. Cerebrospinal fluid (CSF) was inflammatory with increased leukocytes. Magnetic resonance imaging of the brain showed hyperintensities in both cerebellar hemispheres and vermis in Fluid-attenuated inversion recovery (FLAIR) and T2- weighted sequences. Infectious disorders were ruled out, but positivity for anti-Homer-3 antibodies was detected in the CSF, but not in the serum. Additionally, low titers of voltage-gated calcium channel (VGCC) antibodies were found in the serum. Treatment with intravenous (IV) corticosteroids did not provide meaningful clinical improvement; however, the patient achieved almost complete recovery (modified Ranking Scale score: 1) following IV immunoglobulin.ConclusionAnti-Homer-3 cerebellar ataxia with encephalopathy should be considered within the differential diagnosis of acute inflammatory cerebellar disease in children and it may coexist with VGCC antibodies.
BackgroundEncephalitis has been recognized in patients with autoimmunity related to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) antibodies; however, patients with meningoencephalitis associated with those antibodies have been rarely identified in the medical literature. We aimed to define the frequency, clinical features, response to therapy, and functional outcomes of patients with meningoencephalitis associated with GAD antibodies.MethodsWe retrospectively studied consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder from January 2018 to June 2022. The modified Rankin Scale (mRS) was used to assess the functional outcome at the last follow-up.ResultsWe evaluated 482 patients with confirmed autoimmune encephalitis during the study period. Four among the 25 patients with encephalitis related to GAD65 antibodies were identified. One patient was excluded owing to the coexistence of NMDAR antibodies. Three male patients aged 36, 24, and 16 years had an acute (n = 1) or subacute (n = 2) onset of confusion, psychosis, cognitive symptoms, seizures, or tremor. No patient had fever or clinical signs of meningeal irritation. Mild pleocytosis (<100 leukocytes/106) was identified in two patients, whereas one patient had normal CSF. Following immunotherapy with corticosteroids (n = 3) or intravenous immunoglobulin (n = 1), significant improvement was observed in all three cases, achieving a good outcome (mRS 1) in all cases.ConclusionMeningoencephalitis is an uncommon presentation of GAD65 autoimmunity. Patients present with signs of encephalitis but with meningeal enhancement and have good outcomes.
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