The Anti-NMDA Receptor Encephalitis Foundation Newsletter

Objective Cognitive dysfunction is a core symptom of NMDAR encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here,…

 




Autoimmune encephalitis occurred occasionally among a cohort of patients after having had COVID-19, according to study results published in Neurology. “The frequency of autoimmune encephalitis (AE) associated with SARS-CoV-2 is unknown,” Cristina Valencia-Sanchez, MD, PhD, of the…

 




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We report a case of Anti-N-methyl-d-aspartate receptor (Anti-NMDAR) encephalitis patient with SARS-CoV-2 infection. A 30 years-old female who was hospitalized on 17th March 2020, with agitation, dysarthria and hallucinations for 3 days. On 20th March 2020 patient started with a fever (>37.5 °C) and chills. A SARS-CoV-2 RT-PCR resulted positive. She was quarantined and treated with Hydroxychloroquine and Lopinavir/Ritonavir. Electroencephalogram showed left fronto-temporal lateralized epileptiform discharges and delta brush pattern. Cerebrospinal fluid (CSF) analysis show hyperproteinorraquia (54.5 mg/dl) and lymphocytic pleocytosis (leukocytes 44/μl with 90% lymphocytes). MRI acquired on April 2020 showed subtle hyperintensity of the left hippocampus on the Fluid-attenuated inversion recovery (FLAIR) sequence (Fig. 1 ). Two days later both CSF and blood test showed presence of NMDAR antibodies. Patient was treated with methylprednisolone, antiepileptic drugs and immunotherapy. Once cardiothoracic and neurologic symptomatology was stabilized, patient was discharged from the hospital on May 2020 with Rituximab and a neurorehabilitation program. On the follow-up, on September 2020, patient who showed new-onset mnesic cognitive impairment was studied with a brain 18F-FDG PET that showed a slight asymmetry on the left anterior temporal lobe and hypometabolism defects on the postero-medial left temporal lobe and in the right cerebellar hemisphere (Fig. 2 ). The corregistered imaging with the MRI acquired previously and PET imaging showed a concordance between an increase of signal intensity on the FLAIR image and hypometabolism defect. Patient continued with Rituximab, antiepileptic drugs and neurorehabilitation. On January 2021, a new MRI was performed and an infarction was observed in the right cerebellar hemisphere. Currently patient does not present epileptic seizures and she has mild cognitive impairment. PET quantification showed an asymmetry on left temporal anterior lobe corresponding to hypometabolism asymmetry (Fig. 3 ). Anti-NMDAR encephalitis is one of the most common types of autoimmune encephalitis characterized by antibodies against the GluN1 subunit of this receptor. NMDAR antibodies have a tropism on hippocampal neurons and from this biological effect derives its main clinical features. Patients are usually young adults, predominantly women, who develop progressive symptoms including abnormal behaviour, autonomic dysfunction, and seizures.1 Recognition of Anti-NMDAR encephalitis is important because, despite its severity, most patients respond to immunotherapy.2 Recently, COVID-19 has been described as a cause of autoimmune encephalitis including Anti-NMDAR encephalitis.1 In autoimmune encephalitis, SARS-CoV-2 virus causing COVID-19 disease leads to brain damage due to the cytokine storm mediated by interleukin mostly IL-2 and IL-6 in the CSF.2 This mechanism may be the cause of hypometabolism in PET related to cortical damage.3 Early hypermetabolism has been described in the mesial temporal areas and could be a marker of active inflammatory process of limbic encephalitis. On the contrary, the hypometabolism pattern including temporal, parietal and occipital areas was observed in the follow-up.3 In addition, MRI FLAIR signal abnormity has been described in autoimmune encephalitis caused by COVID-19 in the temporal lobe and in the basal ganglia.1 The regional infarct involving the right cerebellar cortex may be associated to cerebral thrombotic microangiopathy1, 2 as a complication in our case.

 




Results: Eighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive (April-December 2020). Diagnoses were: AE, 2; post-acute sequelae of SARS CoV-2 infection [PASC], 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non-COVID-19 relatable neurological diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases which overlapped) representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n=1), probable (n=1), or possible (n=3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46-63), 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n=5], seizures [n=2], rhombencephalitis [n=1], aphasia [n=1], and ataxia [n=1]). No ADEM cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses.

 




In adult-onset NMDAR-antibody encephalitis, psychiatric features are typically the presenting complaint, with patients often needing mental health assessments before a neurology consultation. In our experience, relatively isolated psychiatric features occur in these patients only at disease onset. Subsequently, within a few days, they are rapidly accompanied by more traditional neurological abnormalities including delirium, amnesia and seizures. Nevertheless, careful consideration of the psychopathology can help in differentiating NMDAR-antibody encephalitis from primary psychiatric disease. NMDAR-antibody encephalitis often presents with a complex phenotype spanning classically distinct psychiatric diagnostic categories, including domains of mood, psychosis, behaviour and catatonia, the latter also seen with gamma aminobutyric acid A receptors (GABAAR)-antibodies.10 By contrast, early ‘transdiagnostic’ presentations are unusual in most primary psychiatric diseases. Overall, the complex psychiatric phenotype at onset combined with polysymptomatic neurological disease and a polymorphic movement disorder, discussed in detail later, creates a multifaceted presentation highly characteristic of NMDAR-antibody encephalitis. These features contrast markedly to the poorly circumscribed clinical syndrome of neuropsychiatric systemic lupus erythematosus, in which NMDAR-antibodies have also been reported. However, by contrast to antibodies which target native neuronal surface epitopes, those from patients with neuropsychiatric systemic lupus erythematosus have been found to show intrinsic ‘stickiness’, which is not NMDAR-specific, and hence have limited diagnostic value.11

 




Objective: To explore the immune characteristics and short-term prognosis of children with autoimmune encephalitis (AE), then to analyse the relationship between them. Methods: A total of 78 children with AE were identified through the clinic database a…

 




Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or…

 




Background: Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. CASPR2 antibody-associated autoimmune encephalitis is mostly reported …

 




Introduction Seizures of autoimmune etiology may occur independent of or predate syndromes of encephalitis. We report a child with “pure” autoimmune epilepsy followed up for 7 years to highlight long-term effects of this epilepsy and the importance of early initiation and appropriate escalation of…

 




Abstract Objective To determine whether the metabolites of Kynurenine pathway (KP) could serve as biomarkers for distinguishing between viral CNS infections and autoimmune neuroinflammatory disease…

 




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