The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

It was concluded that an absence of fidgety movements that goes along with subtle dysmorphic features indicates an increased risk of maldevelopment and justifies the need to refer for genetic evaluation with the potential of facilitating earlier diagnosis.

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Summary:Purpose: To report a previously undescribed adverse effect, IgA/IgG subclass deficiency associated with zonisamide (ZNS) therapy.Methods: Serum IgA and IgG subclass levels were determined by the turbidimetric immunoassay and enzymelinked immunosorbent assay, respectively, in a 2-year-old boy with postmeningitis sequelae who was treated by ZNS.Results: Four months after initiation of ZNS, combined deficiency of IgA and IgG2 was noted. After cessation of ZNS, serum IgA level was promptly increased. IgG2 level was gradually increased, but remained subnormal after 7 months.Conclusions: This case documents, for the first time, the action of ZNS on IgG immune system as well as IgA system.If patients with ZNS therapy showed IgA deficiency and recurrent infections, it is preferable to check serum IgG subclass concentrations as well. Key Words: ZonisamideEpilepsy-IgA deficiency-IgG subclass-Phenytoin.Secondary IgA deficiency has been reported in patients treated with various drugs such as epileptic drugs (AEDs), D-penicillamine, gold, and sulfasalazine (1,2). Combined deficiency of IgA and IgG subclasses has been observed in association with phenytoin (PHT) and sulfasalazine therapies (3,4). There have been only a few reports of IgA deficiency or low IgA levels in children treated with a new benzisoxazole AED: zonisamide (ZNS) (5,6). We report a patient who developed IgA and IgG2 subclass deficiency associated with ZNS therapy. CASE REPORTAt age 17 months, an otherwise healthy boy developed bacterial meningitis. He was treated with antibiotic agents and phenobarbital (PB). At that time, serum immunoglobulin levels were normal (Table 1). Because the boy had postmeningitis sequelae, i.e., spastic quadriplegia, epilepsy, and mental retardation, he was transferred to our division for rehabilitation. After discharge, he was treated with PB (40 mg/ day; serum concentration, 12.3 pglml) and muscle relaxants. At age 2 years 3 months, ZNS (80 mg/ day) was added to his regimen because of secondarily generalized seizures and increases in epileptic discharges on EEG. Four months after initiation of ZNS therapy, a deficiency in serum IgA (<5 mg/dl) and IgG2 (21.0 mg/dl; normal range at age 2-4 years; 58.5-292.1 mg/dl) levels was noted, with decreased serum levels of total IgG (379 mg/dl) ( Table 1). Serum IgG1, IgG3, and IgG4 concentrations were within normal ranges for children of his age (7) (normal range of IgG1, 390.2-955.2 mg/dl; normal range of IgG3,11.4-98.8 mg/dl; normal range of IgG4,1.2-76.7 mg/dl). Total IgG, IgA, and IgM concentrations were measured by turbidimetric immunoassay (8). IgG subclasses were determined by enzyme-linked immunosorbent assay (ELISA) (9). Three examinations during ZNS therapy consistently showed IgA deficiency and decreased total IgG levels. Serum concentration of ZNS was not in the toxic range (15.2 pglml). Because the patient showed no susceptibility to infections, intravenous y-globulin therapy was not initiated. Three weeks after discontinuation of ZNS therapy, serum IgA levels were nor...

Using a two-site enzyme-linked immunosorbent assay, we measured nerve growth factor (NGF) levels in cerebrospinal fluid (CSF) from 40 patients with or without brain atrophy due to various neurologic disorders. White matter and cortical atrophies were assessed by frontal horn index (FHI) and subarachnoid space area/inner skull space area (SSA/ISSA) ratio, respectively. CT findings of 40 patients were classified into 4 grades: normal (< mean + 2SD), grade I (mean + 2SD < or = or < mean + 4SD), grade II (mean + 4SD < or = < mean + 8SD), and grade III (mean + 8SD < or =). NGF levels in CSF were significantly elevated in 3 of 6 patients with grade III cortical atrophy and normal in 2 with grade II atrophy, 4 with grade I atrophy and 28 without atrophy. Cortical atrophy was progressive in the 3 with NGF elevation in CSF. With respect to white matter atrophy, NGF elevation was observed in none of 3 with grade III white matter atrophy, two of 4 with grade II atrophy, none of 3 with grade I atrophy and one of 30 without atrophy. The symptoms of the two of three with NGF elevation were progressive at the time of obtaining the CSF samples, while those of other patients without NGF elevation were non-progressive. The present study suggests that NGF elevation in CSF may reflect extensive cortical degenerative change.

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