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Background: Antibody-mediated and cytotoxic T cell-mediated pathogenicity have been implicated as the autoimmune pathophysiologic mechanisms in Rasmussen's encephalitis., Methods: The authors investigated autoantibodies against the NMDA glutamate receptor (GluR) epsilon2 subunit and their epitopes in serum and CSF samples from 15 patients with chronic epilepsia partialis continua (EPC), 17 with West syndrome, 10 with Lennox-Gastaut syndrome, and 11 control subjects., Results: In 15 patients with chronic EPC, we detected NMDA-type GluR epsilon2 autoantibodies in histologically proven Rasmussen's encephalitis (3/3 patients), clinical Rasmussen's encephalitis (6/7 patients), acute encephalitis/encephalopathy (2/3 patients), and nonprogressive EPC (2/2 patients). Serum IgM autoantibodies were found in the early phase of EPC and became negative later in four patients. The autoantibodies were not detected in West syndrome, Lennox-Gastaut syndrome, or controls. Among 10 patients with histologically proven or clinical Rasmussen's encephalitis, epitope analyses showed that the autoantibodies were predominantly against C-terminal epitopes and rarely against N-terminal epitope, with inconsistency in profile during the courses of disease. Epitope recognition spectrum of autoantibodies was broader in CSF than in serum, and the serum or CSF profile showed an increase in number of epitopes as disease progressed in some patients., Conclusions: The presence of autoantibodies against NMDA GluR epsilon2 suggests autoimmune pathologic mechanisms but is not a hallmark of Rasmussen's encephalitis. Patients with Rasmussen's encephalitis may have autoantibodies against several neural molecules, and these autoantibodies may be produced in the CNS after cytotoxic T cell-mediated neuronal damage.

Objective: To determine whether frequent seizures and/or hypsarrhythmia may cause neuronal injury in West syndrome., Background: West syndrome is an age-related epileptic syndrome of infancy characterized by clusters of epileptic spasms, a peculiar interictal EEG pattern of hypsarrhythmia, and mental deterioration. Recent clinical studies demonstrated that serum and CSF neuron-specific enolase (NSE)-a marker of neuronal injury-were increased after status epilepticus., Methods: The authors examined serum and CSF NSE levels in 18 newly diagnosed infants (8.4 +/- 2.2 months) with West syndrome (3 cryptogenic, 15 symptomatic). In patients who showed complete resolution of spasms and disappearance of hypsarrhythmia (responders), additional serum NSE levels were determined several weeks after cessation of seizures. Serum NSE levels were obtained from 28 age-matched infants with normal neurologic development (control group), and 10 infants with an acute neurologic insult., Results: There were no significant differences (p > 0.05) in serum NSE levels between the group with West syndrome (12.9 +/- 3.4 ng/mL) and the control group (13.2 +/- 3.1 ng/mL). The serum NSE value in the group with an acute insult (100.3 +/- 67.4 ng/mL) was significantly higher (p < 0.0001) than that for the West syndrome and the control groups. The mean +/- SD CSF NSE level was 7.3 +/- 3.6 ng/mL, which is similar to the reported CSF NSE levels of Japanese infants without neurologic disease. Thirteen responders showed no significant (p > 0.05) change in serum NSE after cessation of epileptic spasms., Conclusion: Normal serum and CSF neuron-specific enolase levels provided no evidence that seizures and/or hypsarrhythmia induced neuronal injury in West syndrome.

Massive infantile spasms (MIS), a seizure disorder unique to infants, is considered an age-dependent response of the immature brain to various insults and stressors. The seizures improve with ACTH and glucocorticoids, both major components of the brain-adrenal axis. We hypothesized that CNS levels of these hormones are abnormal in infants with MIS and studied CSF from 14 infants with MIS and 13 age-matched controls by analysis for corticotropin-releasing hormone (CRH), ACTH, cortisol, and interleukin-1-beta. ACTH levels in CSF of patients were significantly lower than those of controls, but differences in cortisol levels between patients and controls were not statistically significant. CRH levels in both groups were similar and fluctuated diurnally. These results indicate an alteration of specific CNS components of the brain-adrenal axis in MIS.

The mean CSF GABA level in 22 children with infantile spasms was significantly lower than in 35 controls. There was no significant difference between the CSF GABA levels in untreated children and those treated with anticonvulsants, or between uncontrolled and temporarily controlled patients. After treatment with ACTH, CSF GABA levels were lower than before treatment, and seizures disappeared. Brain GABAergic neuronal function may be disturbed in children with infantile spasms, but the decreased CSF GABA level does not directly correlate with the seizures of infantile spasms.

We measured CSF levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) by high-performance liquid chromatography in seven children with infantile spasms and in a group of age- and sex-matched controls. The mean concentration of the serotonin metabolite 5-HIAA was 40% (p less than 0.01) lower in the infantile spasms group as compared with controls; HVA levels were similar in both groups. The data provide additional evidence that serotonin metabolism is abnormal in patients with infantile spasms.