A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and imaging.

Early-onset epileptic encephalopathies include various diseases such as early-infantile epileptic encephalopathy with suppression burst. We experimentally investigated the unique clinicopathological features of a 28-month-old girl with early-onset epileptic encephalopathy. Her initial symptom was intractable epilepsy with a suppression-burst pattern of electroencephalography (EEG) from 7 days of age. The suppression-burst pattern was novel, appearing during sleep, but disappearing upon waking and after becoming 2 months old. The EEG showed multifocal spikes and altered with age. Her seizures demonstrated various clinical features and continued until death. She did not show any developmental features, including no social smiling or head control. Head MRI revealed progressive atrophy of the cerebral cortex and white matter after 1 month of age. (123)IMZ-SPECT demonstrated hypo-perfusion of the cerebral cortex, but normo-perfusion of the diencephalon and cerebellum. Such imaging information indicated GABA-A receptor dysfunction of the cerebral cortex. The genetic analyses of major neonatal epilepsies showed no mutation. The neuropathology revealed atrophy and severe edema of the cerebral cortex and white matter. GAD-immunohistochemistry exhibited imbalanced distribution of GABAergic interneurons between the striatum and cerebral cortex. The results were similar to those of focal cortical dysplasia with transmantle sign and X-linked lissencephaly with ARX mutation. We performed various metabolic examinations, detailed pathological investigations and genetic analyses, but could not identify the cause. To our knowledge, her clinical and pathological courses have never been described in the literature.

Magnetoencephalography in the detection of focal lesions in West syndrome.

BACKGROUND: According to the international classification of epilepsy syndromes, West syndrome (WS) is a form of generalized epilepsy. However, it is known that localized lesions can induce WS and that patients with WS often subsequently develop focal seizures. We evaluated such patients using magnetoencephalography (MEG). METHOD: Fourteen patients of 3 months to 6 years of age who had or who had previously had WS were examined. MEGs were recorded using a laying-type whole-cortex MEG system with a 160-channel first-order gradiometer. Twelve-channel electroencephalography (EEG) and one-channel electrocardiography (ECG) were simultaneously recorded. Equivalent current dipoles were estimated at the point of spikes on the EEG. RESULTS: Patients were classified by magnetic resonance imaging (MRI) findings into a focal lesion group (group F, n=7) and a non-focal lesion group (group N, n=7). The dipoles estimated from the MEG were classified into three groups: W, with the dipoles distributed over a wide brain area (n=7); WC, dipoles distributed over a wide area along with a dense dipole distribution in a specific cortical area (n=3); and C, closed dipole distribution in a unilateral cerebral focal area (n=4). Patients were also classified by the stage of the disease during which the MEG was recorded, and by the type of seizure they experienced. Those with hypsarrhythmia examined early in the disease all had pattern W regardless of their lesion group, whereas those examined later exhibited more diverse dipole patterns that corresponded to seizure type. CONCLUSIONS: Dipoles were distributed widely over bilateral cerebral cortex when patients had infantile spasms with hypsarrhythmia whether or not they had focal lesions. The dipole distribution pattern in MEG changed according to changes in seizure type.

[Seizures associated with fever in children of congenital adrenal hyperplasia].

We investigated seizures in 22 children with congenital adrenal hyperplasia (CAH), eight of whom had seizures associated with fever. The follow-up period was 5-18 years. The onset of seizures ranged from 1 to 4 years of age, and the total number of seizures was one to three in all cases. Four cases had seizures twice within 24 hours. None had seizures after 5 years of age. In two of the eight cases, the seizures may have caused by hypoglycemia or hyponatremia, in the remaining six they were considered to be febrile seizures. Three of them had first-degree relatives with febrile seizures. Electroencephalogram was recorded in five cases, with normal results in all of them. One case with febrile status developed localization-related epilepsy later. None showed developmental delay during follow-up. Although seizures in CAH have been ascribed to hypoglycemia and/or metabolic disorders (hyponatremia), our findings implicate unknown factors in the pathogenesis such as excess secretion of corticotropin releasing factor (CRF) under stress, prolonged elevation of CRF during fetus life and linkage between CAH and febrile seizures on the chromosome 6.

[Efficacy of zonisamide in West syndrome].

The efficacy of zonisamide (ZNS) was studied in 16 patients (11 males, 5 females) with West syndrome (WS), symptomatic in 13 and cryptogenic in 3. They did not respond to pyridoxal phosphate (12 cases) or valproate (16 cases). The mean age of onset of WS was 4.4 (2-9) months. ZNS was administered from 3 to 9 months of age (mean 6.1). Four cases (2 cryptogenic and 2 symptomatic) became seizure free. Two had more than 50% seizure reduction. Ten infants remained unchanged or showed less than 50% seizure reduction. In the 4 responders, the effective dose was 4-8 mg/kg (mean 5.8), and the serum ZNS concentration was 10-21 micrograms/ml (mean 13.8). One had relapse of WS after 4 months. Three with normalized EEG remained seizure-free during the follow-up period (12-26 months). One case developed a transient drowsiness, but no serious side effects were observed. These data suggest ZNS may be regarded as a therapy of choice before synthesized ACTH therapy in the management of WS.

[Home mechanical ventilation with nasal intermittent positive pressure ventilation for a boy with congenital central hypoventilation syndrome].

We report a 4-year-old boy with congenital central hypoventilation syndrome (CCHS) successfully treated with home mechanical ventilation with nasal intermittent positive pressure ventilation (NIPPV) during sleep hours. He had had frequent severe apneic attacks from the neonatal period. At 8 months, he was treated with positive pressure ventilation following a tracheostomy. At 4 year and 2 months, NIPPV was attempted because of recurrent respiratory tract infections and cor pulmonale. The tracheostomy was successfully abandoned 6 months later. Adequate ventilation has been maintained for more than 3 years without troubles. NIPPV is an effective and non-invasive treatment of CCHS that it significantly improves the quality of life during daytime.

Screening for PIT1 abnormality by PCR direct sequencing method.

PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene, which encodes a pituitary specific transcription factor Pit-1/GHF-1.PIT1 abnormality has been reported in several patients displaying either complete or incomplete deficiency of thyrotropin (TSH), growth hormone (GH), and prolactin (PRL) in either familial or sporadic cases. To see if there are abnormalities in the PIT1 gene in patients with incomplete TSH, GH, and PRL deficiency, we utilized a PCR direct sequencing method to determine the Pit-1/GHF-1 coding sequence. A total of 15 patients, 1 patient from a family with TSH and GH deficiency, 3 patients with TSH, GH, and PRL deficiency, and 11 patients treated with both human GH (hGH) and thyroid hormone were studied. In one patient of combined pituitary hormone deficiency, the Arg-271-Trp mutation was detected. Since both of the parents did not harbor this mutation, it is a de novo germ line mutation. No mutation was detected in the other patients, showing that PIT1 abnormality is not a frequent cause of GH deficiency.

Amygdala kindling and associated changes of entorhinal responses in suckling rats.

Entorhinal field potential with amygdala stimulation in suckling (16-18 days old) and adult rats was recorded with a tungsten wire electrode (tip diameter 2-5 microns) to study the developmental changes in behavioral seizures and long-term potentiation (LTP) in the responses to amygdala kindling stimulations. Stimulating (twisted enamel-coated wires) and recording electrodes were implanted in anesthetized rats 2-3 days before kindling. The mean amplitude of the responses to test pulses (600 microA, 0.3 Hz) in the sucklings (0.58 mV) was smaller than in the adults (1.32 mV), and latency was about 3.3 ms longer. Kindling stimulations consisted of 0.5-ms monophasic rectangular pulses of 10 Hz with a 10-s train duration; the intensity was the afterdischarge (AD) threshold. Kindling stimulation in the sucklings usually increased the amplitude of the test responses evoked 10 min or 1 h after the kindling stimulation. The increased amplitude persisted for at least 24 h, showing LTP in the synaptic transmission. The LTP was especially prominent in the first kindling stimulation, and the LTP gradually increased with successive stimulations, with gradual progression of AD and the behavioral seizure stage as well. The mean number of kindling stimulations to cause generalized seizures in the suckling rats (10.5) was less than that for adults (12.5), and the continued evolution of LTP over the course of kindling was more or less easier in the sucklings than in the adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of kan-baku-taiso-to (TJ-72) on breath-holding spells in children.

When Kan-baku-taiso-to (TJ-72) (0.1-0.25 g/kg/day) was given to 12 children with breath-holding spells (BHS) of the cyanotic type, the attacks were lessened starting in the second week of administration. There were no side effects even when administration was continued for more than one year. We think that the drug should be given primarily for BHS when the frequency of severe attacks is high and also to patients who did not respond to other medication.

Serial magnetic resonance imaging in subacute sclerosing panencephalitis.

Magnetic resonance (MR) imaging of a 17-year-old girl with subacute sclerosing panencephalitis (SSPE) was done several times to monitor the morphological changes and clinical course of the disease by comparison with computed tomographic (CT) scans. The MR image showed lesions that corresponded to the clinical symptoms in the early stages where no abnormalities appeared on the CT scans. The MR images delineated the extent of abnormal areas more clearly than the CT scans. However, the course of neurological manifestations did not always correspond to the MR findings. Serial MR imaging was useful in the detection and observation of the stages and clinical progress of SSPE.