Possible autoimmune association between herpes simplex virus infection and subsequent anti-N-methyl-d-aspartate receptor encephalitis: a pediatric patient with abnormal movements.

AIM: We describe a child with severe generalized choreoathetosis and anti-N-methyl-d-aspartate receptor encephalitis after herpes simplex virus type 1 encephalitis. Recent evidence supports an autoimmune trigger for anti-N-methyl-d-aspartate receptor encephalitis following a viral infection. This is emerging as a common and potentially treatable autoimmune condition in the pediatric population. PATIENT DESCRIPTION: A 6-month-old girl presented with fever, diarrhea, and partial seizures and was subsequently treated for proven herpes simplex virus type 1 encephalitis. Shortly thereafter, she developed irritability, insomnia, dysautonomia, orolingual and facial choreodystonic movements, spontaneous vocalizations, and choreoathetoid movements of her trunk and limbs. Cerebrospinal fluid analysis confirmed anti-N-methyl-d-aspartate receptor antibodies. Management of her movements required titrated doses of clobazam, valproate, tetrabenazine, and immunotherapy. At 3 months' follow-up, her abnormal movements had completely resolved. CONCLUSIONS: Our patient adds to recent evidence linking a viral trigger for brain autoimmunity. Movement disorders appear early, leading to severe patient and family distress, and pose a serious management dilemma because of a paucity of clinical trials assessing treatments in the pediatric population. Abnormal hyperkinetic movements present early and prominently, requiring a combination of symptomatic and immune-modulating therapies for successful treatment.

Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p=0.004; cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody-positive patients also had evidence of relapsing post-HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity.

Seizures in juvenile Huntington's disease: frequency and characterization in a multicenter cohort.

Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required.

Idiopathic intracranial hypertension in two patients with Alagille syndrome.

Alagille syndrome is an autosomal dominant condition with incomplete penetrance that is associated mostly with hepatic, cardiac, and skeletal abnormalities. In addition, the association of Alagille syndrome with ocular abnormalities is well known and is considered one of the characteristic features of this condition. Most commonly, posterior embryotoxon, glaucoma, or retinopathy has been identified in these children. The authors present 2 patients with Alagille syndrome who, before the age of 3 years old, developed idiopathic intracranial hypertension with documented increased intracranial pressure by lumbar puncture and papilledema, which was responsive to acetazolamide.