Takehiko Okuno

Cerebral atrophy following ACTH therapy.

In a study of 15 patients with infantile spasms and Lennox syndrome 4 (26.7%) showed no cerebral atrophy and 11 (73.3%) showed mild ventricular and sulcal enlargement before ACTH therapy. Ventricular and sulcal enlargement increased soon after ACTH therapy in most patients. Cerebral atrophy was reversible at over 1 month after ACTH therapy. However, in three instances, cerebral atrophy was not reversible, and one patient with infantile spasms had chronic subdural effusion, which appeared to be a complication of treatment with ACTH. Patients on ACTH therapy should be carefully monitored.

Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy.

Purpose: Genetic abnormalities of the gene encoding α1 subunit of the sodium channel (SCN1A), which can be detected by direct sequencing, are present in more than 60% of patients with severe myoclonic epilepsy in infancy (SMEI) or its borderline phenotype (SMEB). Microchromosomal deletions have been recently reported as additional causes of SMEI. This study examines whether such microdeletions are associated with SMEI as well as with SMEB.

Electroclinical Picture of Autosomal Dominant Nocturnal Frontal Lobe Epilepsy in a Japanese Family

Summary: Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first described partial epilepsy syndrome known to be due to a single gene mutation. We found a first Japanese ADNFLE family with a novel mutation of the neuronal nicotinic acetylcholine receptor (nAChR) α4 subunit (CHRNA4) gene. The aim of this report is precisely to describe the electroclinical manifestations of ADNFLE in this family and to compare these findings with those of other families reported previously in the literature.

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

We present an autopsy report on a 14‐year‐old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS), placing emphasis on the mitochondrial enzymatic histochemistry of the 3 types skeletal muscle and cardiomyocytes. Generalized muscular atrophy, cardiac hypertrophy, cerebral cortical laminar necrosis, basal ganglia calcification and liver steatosis were observed. In the skeletal muscles, modified Gomoris trichrome staining demonstrated scattered ragged red fibers, and histochemical staining for mitochondrial enzymes showed intense positivity in the subsarcolemmai zones of some muscle fibers. Some of the hypertrophic cardiomyocytes also showed a ragged red appearance with the modified Gomoris trichrome stain. Histochemical staining for mitochondrial enzymes showed patchy loss of enzymatic activity in the myocardium. Electron microscopically, extreme accumulation of enlarged mitochondria and severe loss of myofibrils was observed in both skeletal muscle fibers and cardiomyocytes. The arteriolar smooth muscle cells also showed a mild increase in mitochondria. Acta Pathol Jpn 39: 599 606, 1989.

Complex I (reduced nicotinamide-adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome

Two infants who had clinical and radiographic findings consistent with Leigh syndrome were found to have deficiency of complex I (reduced nicotinamide-adenine dinucleotide--coenzyme Q reductase) activity. Significant abnormalities were found on computed tomographic scans and magnetic resonance images of the brain. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated, and muscle biopsy specimens showed abnormal mitochondria. These data indicate that Leigh syndrome, as well as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) may result from complex I deficiency.

ACTH therapy in infantile spasms: Relationship between dose of ACTH and initial effect or long-term prognosis

The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage, provided the dose was greater than 0.015 mg (0.6 IU)/kg/day, and the outcome of seizures and electroencephalographic abnormalities; however, ACTH 0.04-0.06 mg (1.6-2.4 IU)/kg/day and a total ACTH dose of 1.1-1.5 mg (44-60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects.

Landau-Kleffner syndrome EEG topographic studies

Spectral and historical topographic mapping of EEG was done on 2 siblings with Landau-Kleffner syndrome. The clinical features of the elder sister were acquired aphasia developed at the age of 5, followed by convulsions a year later, and those of the younger brother were progressive ataxia, hemiparesis, urinary incontinence and convulsions at the age of 4 years and 10 months, followed by acquired aphasia a year later. The most prominent spectral mapping features were high spectral powers of delta, theta and alpha waves over the fronto-centro-parietal area. The power of alpha and beta wave bands, reflecting sharp or spike waves, varied spatio-temporally over the central, parietal, temporal and frontal areas. The historical mapping revealed variabilities of paroxysmal discharges in modes of propagation. These results suggested that electrophysiological dysfunction of the fronto-centro-parietal areas associated with markedly unstable paroxysmal discharges is the main feature of Landau-Kleffner syndrome.

SEQUENTIAL CT STUDIES OF 24 CHILDREN WITH INFANTILE SPASMS ON ACTH THERAPY

Sequential CT studies were performed in 24 patients with infantile spasms, before, during and after ACTH therapy, in order to analyze the relationship between the dose of ACTH and changes in CT scan findings. In six cases CT scans did not return to their original state after ACTH therapy. Two illustrative cases are reported. There was a good correlation between the total dose of ACTH and the percentage decrease of brain parenchyma. It is concluded that ‘cerebral atrophy’ on CT scans may represent an accumulative effect of ACTH and that ACTH should be given with the utmost discretion, and in as low a dose as possible.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.

Pituitary Hyperplasia Due to Hypothyroidism.

Two cases of hypothyroidism with computed tomographic evidence of enlargement of the pituitary gland are reported: in both the enlargement disappeared after treatment. These findings are in agreement with the previously reported observation that an increase of TSH production in primary hypothyroidism may lead to pituitary hyperplasia.