ABSTRACT
N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) can contribute to neurological relapse after herpes simplex virus encephalitis (HSE). We describe a child with NMDAR-Ab encephalitis after HSE, which was recognized and treated early. We discuss the case in the context of existing reports, and we propose a modified immunotherapy strategy to minimize risk of viral reactivation.
Subject(s)
Acyclovir/therapeutic use , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy , Encephalitis, Herpes Simplex/complications , Encephalitis, Herpes Simplex/therapy , Immunosuppression Therapy/methods , Receptors, N-Methyl-D-Aspartate/immunology , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/rehabilitation , Antiviral Agents/therapeutic use , Autoantibodies/immunology , Clonidine/therapeutic use , Diazepam/therapeutic use , Encephalitis, Herpes Simplex/diagnostic imaging , Encephalitis, Herpes Simplex/rehabilitation , Encephalomalacia/diagnostic imaging , Encephalomalacia/etiology , Female , Fever/etiology , Humans , Immunocompromised Host/drug effects , Immunocompromised Host/immunology , Infant , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/etiology , Movement Disorders/etiology , Neurological Rehabilitation , Pakistan , Paresis/etiology , Phenobarbital/therapeutic use , Phenytoin/therapeutic use , Plasmapheresis , Seizures/etiology , Trihexyphenidyl/therapeutic use , United Kingdom , Valproic Acid/therapeutic useABSTRACT
OBJECTIVE: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. METHOD: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody-positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. RESULTS: THREE DISTINCT CLINICORADIOLOGIC PHENOTYPES WERE RECOGNIZED: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. CONCLUSION: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease.
