Investigations in GABAA receptor antibody-associated encephalitis

GABA-A receptor; Encephalitis; AntibodiesReceptor GABA-A; Encefalitis; AnticossosReceptor GABA-A; Encefalitis; AnticuerposOBJECTIVE: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis. METHODS: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques. RESULTS: Patients' median age was 40.5 years (interquartile range 48.5 [13.75-62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical-subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures (p = 0.007) and movement disorders (p = 0.01) and less likely to have a tumor (p = 0.01). The main epitope targets were in the α1/β3 subunits of the GABAAR. CONCLUSIONS: Anti-GABAAR encephalitis is characterized by frequent seizures and distinctive multifocal cortical-subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment

Clinical Features and Inflammatory Markers in Autoimmune Encephalitis Associated With Antibodies Against Neuronal Surface in Brazilian Patients

Acute encephalitis is a debilitating neurological disorder associated with brain inflammation and rapidly progressive encephalopathy. Autoimmune encephalitis (AE) is increasingly recognized as one of the most frequent causes of encephalitis, however signs of inflammation are not always present at the onset which may delay the diagnosis. We retrospectively assessed patients with AE associated with antibodies against neuronal surface diagnosed in reference centers in Northeast of Brazil between 2014 to 2017. CNS inflammatory markers were defined as altered CSF (pleocytosis >5 cells/mm3) and/or any brain parenchymal MRI signal abnormality. Thirteen patients were evaluated, anti-NMDAR was the most common antibody found (10/13, 77%), followed by anti-LGI1 (2/13, 15%), and anti-AMPAR (1/13, 7%). Median time to diagnosis was 4 months (range 2–9 months). Among these 13 patients, 6 (46.1%) had inflammatory markers and when compared to those who did not present signs of inflammation, there were no significant differences regarding the age of onset, time to diagnosis and modified Rankin scale score at the last visit. Most of the patients presented partial or complete response to immunotherapy during follow-up. Our findings suggest that the presence of inflammatory markers may not correlate with clinical presentation or prognosis in patients with AE associated with antibodies against neuronal surface. Neurologists should be aware to recognize clinical features of AE and promptly request antibody testing even without evidence of inflammation in CSF or MRI studies

A patient with a long history of relapsing psychosis and mania presenting with anti-NMDA receptor encephalitis ten years after first episode

Anti-N-methyl- D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune disorder, in which antibodies target NMDARs in the brain, leading to their removal from synapses. Early in the disease course, patients often present with marked psychosis and mood disturbances (i.e. mania, depression), explaining why most of these patients are first seen by psychiatrists. Hence, autoimmune encephalitis is receiving growing attention from psychiatry, mainly owing to concerns over misdiagnosing immunomediated and potentially curable disorders as primary psychiatric disorders, such as schizophrenia or major depressive disorder. Although anti-NMDAR encephalitis occurs in the context of new-onset psychiatric symptoms, there is a lack of information on differential diagnosis and treatment of this disorder after a long-term diagnostic history of functional psychiatric disorders. We report a case of a patient with a long history of bipolar affective disorder evolving with anti-NMDAR encephalitis, initially misdiagnosed as non-organic psychosis

Native Valve Endocarditis due to Enterococcus hirae Presenting as a Neurological Deficit

Enterococcus hirae is a rare isolate in clinical specimens. We describe a case of native aortic valve endocarditis in a 56-year-old man. This is the third reported case of endocarditis due to this organism, the first without recurrence of endocarditis and the first presenting as a neurological deficit

A successful case of anti-NMDAR encephalitis without tumor treated with a prolonged regimen of plasmapheresis

ABSTRACT Anti-NMDA receptor encephalitis is a severe but treatable autoimmune disease of the CNS. However, the use of immunotherapy and long-term outcomes have yet to be defined for this disease. We describe a case of an 18-year-old male diagnosed with anti-NMDAR encephalitis not associated with tumor, which did not respond to initial treatment with immunoglobulin, followed by corticosteroids, cyclophosphamide and evolved with significant clinical improvement after a prolonged course of plasmapheresis. Although it is not possible to affirm the good outcome was due solely to the prolonged plasmapheresis regimen, recently published data shows that improvement may take weeks or months to occur. This case discloses another therapeutic possibility for patients with refractory disease who fail to respond to recommended first-line and second-line therapy