Sumiyoshi Yokoyama

Thyroid Function in Children with Long-Term Anticonvulsant Treatment

Thyroid functions were studied in 287 children given long-term treatment with anticonvulsants. Of these 287 patients, 26 were treated with carbamazepine (CBZ) alone, 63 with phenobarbital (PB) alone, 66 with sodium valproate (VPA) alone and 132 with combination therapy. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were decreased after more than 3 years of treatment with CBZ. The regression line of serum T4 concentrations against serum CBZ concentrations indicated a negative correlation. Serum T3 and T4 concentrations were decreased after more than 6 years of treatment with PB, although there was no statistical significance in the relationship between serum T4 and PB concentrations. There was no significant decrease in serum T3 or T4 concentration in patients treated with VPA. Serum-free T4 and thyroxine-binding globulin were decreased and serum thyrotropic hormone concentration was increased in patients with low serum T4 concentrations. We conclude that thyroid functions should be examined in children given long-term treatment with anticonvulsants.

Vascular involvement in benign infantile mitochondrial myopathy caused by reversible cytochrome c oxidase deficiency

A 1-month-old Japanese girl had profound generalized weakness, hypotonia, and severe lactic acidosis. The infant improved gradually: she held her head at 9 months, learned to walk by 15 months. At the first muscle biopsy at 11 weeks of age, the specimen was characterized by numerous ragged-red fibers and decreased enzyme activity on cytochrome c oxidase (COX) staining. Electron microscopic findings were characterized by the presence of excessive abnormal mitochondria not only in skeletal muscle fibers but also in blood vessels. Vascular abnormalities consisted of an increased number of enlarged mitochondria in endothelial and smooth muscle cells of small arteries. Biochemical analysis showed an isolated defect of COX activity, which was only 16% of the mean control level. At the second biopsy at 44 months of age, the COX activity had increased to normal in the entire specimen. On electron microscopy, the abnormal mitochondria present on the first biopsy specimen had disappeared both in muscle fibers and blood vessels; nearly all mitochondria were morphologically normal at the second biopsy. Now at 5 years of age she can run and does not show muscle weakness. We report reversibility of abnormal mitochondria with age not only in skeletal muscle fibers but also in blood vessels in a patient, who had reversible COX deficiency with a benign clinical course.

A simple method to diagnose adrenoleukodystrophy using a dried blood spot on filter paper

A new, simple method for the diagnosis of adrenoleukodystrophy (ALD) using a dried blood spot sample, is described. Fatty acid from the dried blood spot was extracted and methylated simultaneously with HCl-methanol. Fatty acid methyl esters were analyzed by gas chromatography-mass spectrometry. Fatty acid compositions of the blood spot from four patients with ALD and five healthy controls were determined from the mass chromatograms of the m/z 143 ion, [(CH2)6 COOCH3]+. The ratios of tetracosanoic acid to docosanoic acid (C24:0/C22:0) and hexacosanoic acid to docosanoic acid (C26:0/C22:0) were significantly greater in ALD patients than in the controls. The fatty acid composition of the dried blood spot did not change at room temperature within a week. Since the specimens can be sent by mail, this method could be applied to the screening of ALD.

Adrenoleukodystrophy without adrenal insufficiency and its magnetic resonance imaging

SummaryFatty acids of plasma and erythrocyte membrane sphingomyelin were determined by gas chromatography-mass spectrometry in adrenoleukodystrophy (ALD) without adrenal insufficiency. Mass chromatogram tracing with the ion at m/z 143 [(CH2)6 COOH3]+ showed increases of saturated very long chain fatty acids in plasma and erythrocyte membrane sphingomyelin in ALD. The C26:0/C22:0 ratios in plasma were 0.121, 0.057 and 0.007 in cases 1 and 2, and a control subject, respectively. The C26:0/C22:0 ratios in erythrocyte membrane sphingomyelin were 0.386, 0.211 and 0.093 in cases 1 and 2 and the control subject, respectively. The demyelinating process of ALD was clearly observed in both the inversion recovery 2100/500 and spin echo 2100/80 scans on magnetic resonance imaging. The magnetic resonance image in case 1 revealed widespread demyelinated lesions, involving almost the entire cerebrum and cerebellum, at 4 years after the onset, while that in case 2 revealed demyelinated lesions mainly limited to parieto-occipital areas at 1 year after the onset.

Childhood form of adrenoleukodystrophy in the sucking infant

The childhood form of adrenoleukodystrophy (ALD) in a sucking infant was discovered before the appearance of clinical symptoms. C24:0/C22:0 and C26:0/C22:0 ratios in umbilical cord plasma were significantly higher so that very long-chain saturated fatty acid-restricted milk was given. Ultrastructural study on biopsied rectal mucosa revealed rectilinear and/or curved electron-lucent clefts in the histiocytes at 3 months of age, which were also recognized in the elder brother and another boy with symptoms of ALD. However, magnetic resonance imaging and T1 and T2 values were within the normal range in cerebral gray matter, cerebral white matter, caudate nucleus, internal capsule, and thalamus.

MRI Findings in Early Infantile Epileptic Encephalopathy with Suppression‐Burst

Since early infantile epileptic encephalopathy with suppression-burst (EIEE) , which was characterized by an early onset, frequent tonic spasms, suppression-burst on EEG, poor responses to various treatments and a grave outcome, was first described by Ohtahara in 1976, there have been several reports on its etiology and clinical features. In the past three years, we have found four patients with EIEE in whom the definite etiology was unknown. This study deals with a follow-up study on magnetic resonance imaging (MRI) findings in the four patients with EIEE to clarify the developmental process in the EIEE brain. Patients and Methods

Effect of Long‐Term Treatment with Anticonvulsants on Thyroid Functions in Children

A total of 287 patients who received various anticonvulsants was studied. The ages ranged from one to 29 (mean % SD, 11.4 4 5.4). Of the 287 patients, 26 were treated with carbamazepine (CBZ) alone, 63 with phenobarbital (PB) alone, 66 with sodium valproate (VPA) alone and 132 with combination therapy. All the patients were classified into four groups according to the duration of treatment with anticonvulsants. Group A; 1-2 years, €3; 3-5 years, C; 6-9 years, and D; more than 10 years. Twentysix euthyroid epileptic children who had not received any anticonvulsants were used as controls. The serum triiodothyronine (T3) and thyroxine (T4) concentrations and triiodothyronine resin uptake values ( T3U) were measured. The thyroid functions of these four groups were compared with those of the controls. Then, the serum thyrotropic hormone (TSH), free TS, free T, and thyroxine-binding globulin (TBG) concentrations, antithyroid antibodies and basal metabolic rates (BMR) were measured in the patients whose serum T, concentrations were below 2.5 SD of the mean for the controls (below 5.3 pg/dl).

A study on anticonvulsant-induced rickets and treatment.

当科で3年以上抗てんかん剤を服用している患児92例につき血清Ca, P, Al-p, 25-OH-D値を測定した。更に92例中82例にMD法によりΣGS/D値を求めた。1) Caは21例 (22.8%), 25-OH-D値は17例 (18.5%) が異常を示し, 両者共に服薬年数が長い程異常を示す比率が高かった。2) ΣGS/D値は82例中11例 (13.4%) が異常を示しその殆どが7年以上の長期多剤服用者であった。3) ΣGS/D値の異常と25-OH-D値の異常とは有意の相関を示した (P<0.01)。次に25-OH-D値またはΣGS/D値が異常を示した症例のうち16例に対して1α-OH-D3製剤を18ヵ月にわたり投与し経時的に治療効果を検討した。4) 1α-OH-D3の投与により血清Ca値は3ヵ月で有意に上昇し, 25-OH-D値は6カ月で正常に復した。5) ΣGS/D値は健常人の回帰直線を上回る改善を示した。以上の結果より, くる病発症の要因として多剤の抗てんかん剤を長期に服用することが考えられ, 早期発見には血清Ca, 25-OH-DとともにΣGS/D値の検索が有用であり早期治療として1α-OH-D3は有効であると思われた。

Computed Tomography (CT) in Childhood Epilepsy

The subjects for this study consisted of 200 children, who were diagnosed as epilepsy, and they have been treated at the Department of Pediatrics of Kobe University. Of our 200 patients studied, 65 had a generalized tonic-chic seizure without the focal onset, 24 had infantile spasms, 36 had the Lennox syndrome, and 75 had other seizure disorders. An EM1 1010 scanner was used in our study. The CT findings were classified according to the location (diffuse, focal, hemisphere) and the kind of lesions. The EEG findings were also classified in the same manner as the CT findings.