Etsuo Ohtaki

Acute disseminated encephalomyelitis after Japanese B encephalitis vaccination

A 6-year-old girl (Patient 1) and a 5-year-old boy (Patient 2) with acute disseminated encephalomyelitis after Japanese B encephalitis vaccination are reported. Drowsiness, paresthesias, and gait disturbance were observed at 14 days (Patient 1) and 17 days (Patient 2) after the vaccination; however, transient impairment of visual acuity was only found in Patient 1. Laboratory examinations revealed slow theta waves on electroencephalography and elevated myelin basic protein in the cerebrospinal fluid in both patients. The most striking feature on magnetic resonance imaging was the combination of white matter lesions and abnormal intensity signals of the thalamus. The administration of oral prednisolone (2 mg/kg/day) markedly improved the clinical findings and abnormal magnetic resonance imaging findings. A similar magnetic resonance imaging finding of abnormal intensity of the thalamus with deep white matter lesions has been reported in patients with Japanese B encephalitis; therefore, thalamic lesions may be related to the naturally occurring encephalitis.

Focal cytochrome c oxidase deficiency in various neuromuscular diseases

To determine whether focal cytochrome c oxidase (CCO) deficiency characterized by scattered fibers with absent CCO activity among normal fibers was a specific finding for mitochondrial myopathies, we studied 389 muscle biopsies from various neuromuscular diseases other than mitochondrial myopathies. Focal CCO deficiency was found in 14 biopsies: 5 of 26 patients with myotonic dystrophy, 3 of 19 with nemaline myopathy, 1 of 7 with distal myopathy with rimmed vacuole formation, 3 of 22 with limb-girdle muscular dystrophy, 1 of 9 with amyotrophic lateral sclerosis, one of 79 with Duchenne muscular dystrophy. Focal CCO deficiency is known to be a crucial finding for chronic progressive external ophthalmoplegia, but it can also be seen in a variety of other neuromuscular disorders, probably as a secondarily induced phenomenon.

CSF β-Endorphin Levels in Patients with Infantile Autism

We measured CSF levels of β-endorphin, an opioid hormone, in 19 patients with infantile autism and in 3 patients with Rett syndrome, and compared them with control values. In infantile autism, CSF levels of β-endorphin did not differ significantly from those of age-matched controls. There was no significant correlation between CSF levels and clinical symptoms, including self-injurious behavior, pain insensitivity, and stereotyped movement. However, CSF levels of β-endorphin were significantly higher in the patients with Rett syndrome than in the control (p < .05). Data suggest that neurons containing β-endorphin may not be involved in patients with infantile autism. Thus, there is no relationship between dysfunction of brain opioid and autism.

Tissue specificity in cytochrome c oxidase deficient myopathy.

Biopsied muscles were treated in 2 ways to demonstrate cytochrome c oxidase (CCO) activity on electron microscopy: (1) one to several muscle fibers were teased off the biopsy in buffer solution after glutaraldehyde fixation, (2) 20-30-microns thick cryostat sections were placed on precooled glass slides and fixed in glutaraldehyde solution at room temperature. After rinsing in buffer, the teased fibers and cryostat sections were stained with cytochrome c oxidase. In both procedures, almost all mitochondria in control muscle fibers stained positively. In CCO deficiency, the enzyme activity differed from tissue to tissue indicating marked tissue specificity. In the fatal infantile form enzyme activity in muscle fibers was absent, but present in fibroblasts, endothelial cells and smooth muscle arterial cells. The enzyme activity in other forms differed from cell to cell, but individual mitochondria in a given cell examined in cross-section showed uniform CCO activity, indicating that there was no intracellular mosaicism of enzyme positive and negative mitochondria.

Decreased cerebrospinal fluid levels of β-phenylethylamine in patients with Rett syndrome

To clarify the mechanism of brain impairment in Rett syndrome, we measured the cerebrospinal fluid levels of β‐phenylethylamine (PEA) in 17 patients with Rett syndrome. Findings were compared with those obtained in age‐matched controls and diseased controls. The cerebrospinal fluid level of PEA was significantly lower in patients with Rett syndrome than in the controls (31% of control values). The alteration in the cerebrospinal fluid level of PEA may reflect dopamine system impairment in Rett syndrome. Ann Neurol 2000;47:801–803

The rett syndrome and CSF lactic acid patterns

We investigated both blood and cerebrospinal fluid (CSF) lactate and pyruvate levels in seven girls with the Rett syndrome (RS) and evaluated the relationship between CSF lactate and pyruvate levels and the clinical manifestations, particularly seizures, anticonvulsant medication, and breathing dysfunction including breath holding, apnea and hyperventilation. Elevated lactate and pyruvate levels in CSF with normal serum lactate were found in two RS patients. Elevated CSF lactate correlated significantly with the clinical occurrence of hyperventilation (P0 = 0.048, Fisher exact probability). We measured native and dichloroacetate (DCA)-activated pyruvate dehydrogenase (PDH) complex activities in two patients (#1 and 2) using cultured lymphoblastoid cell lines which were transformed by EB virus and the results were normal. We also analyzed CSF citric acid intermediates from 7 RS patients including citric acid, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate. These concentrations were not significantly different from those control patients (N = 21). An elevated lactate level may be a clue to clarify the etiology of RS.

Cerebrospinal fluid biopterin and biogenic amine metabolites during oral R-THBP therapy for infantile autism

Treatment with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) has been suggested to improve autistic behavior. Cerebrospinal fluid (CSF) levels of total biopterin, oxidized and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were measured in 14 autistic children and 18 controls to clarify the mechanism of action of R-THBP. The 14 autistic children received R- THBP orally at 1 mg/kg per day; 7 children showed clinical improvement (responders) and the other 7 patients did not (nonresponders). There were no significant differences between responders, nonresponders, and controls in the CSF levels of the metabolites before R- THBP administration. When lumbar puncture was repeated in 6 autistic children in the 24th week of R-THBP therapy, there was no significant change in the CSF levels of any metabolites.

Serial magnetic resonance images in a patient with congenital sensory neuropathy with anhidrosis and complications resembling heat stroke

We report the results of serial computerized tomography (CT) and magnetic resonance imaging (MRI) in a 9-month-old Japanese girl with the rare disorder, congenital sensory neuropathy with anhidrosis (CSNA). She developed a prolonged high fever, anorexia, and weight loss with laboratory findings of hemoconcentration and elevated levels of GOT, LDH and creatine phosphokinase (CK) in May 1995, and was hospitalized. The cerebrospinal fluid (CSF) was normal on admission. Elevation of CSF myelin basic protein on the 16th hospital day suggested a destruction of the myelin sheath. The first MRI performed on the 16th hospital day revealed no marked abnormalities when the patient exhibited a high fever, generalized tonic-clonic convulsions, and impaired consciousness. The patient had a persistent high fever, and developed a second generalized tonic clonic convulsion and became comatose. A second MRI on the 20th hospital day showed a bilateral symmetrical paracentral hypo-intensity of the white matter with occipital hypo-intensity on T2-weighted images. MRI findings were considered to represent the complications of the high fever with a loss of water from the cerebral cortices and deep white matter. MRI and CSF findings indicated the presence of brain damage due to the high fever.

Turner Syndrome and Occlusion of the Internal Carotid Artery

A 2-year-old girl with Turner syndrome was admitted with left hemiplegia and left facial palsy. Serial cranial computed tomographic scan demonstrated multiple cerebral infarctions in the right putamen and right medial cortical areas. Single photon emission computed tomographic scan revealed hypoperfusion from the right frontal to the right temporal area. Right carotid angiography showed narrowing and occlusion of the right internal carotid artery at the sphenoidal portion. Collateral circulation was not detected between the external and internal carotid arteries. Left carotid angiography revealed that the left anterior artery was narrow, and that the left internal carotid artery provided blood to the right internal carotid artery through the anterior communicating artery. These findings suggested that the cerebrovascular abnormality might be due to congenital hypoplasia of arteries in this patient. The unusual combination of cerebral infarction and Turner syndrome was reported. (J Child Neurol 1993;8:412-415).

Case of von Recklinghausen Disease Associated With Cerebral Infarction

References 1. Brown GK, Brown RM, Scholdem RD, et al: The clinical and biochemical spectrum of human pyruvate dehydrogenase complex deficiency. Ann N YAcad Sci 1989;573:360-368. 2. Robinson BH: Lactic acidemia, in Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic Basis of Inherited Disease, 6th ed. New York, McGraw-Hill, 1989, pp 869-888. 3. Duran M, Wadman SK: Thiamine-responsive inborn errors of metabolism. J Inherited Metab Dis 1985;8(Suppl 1):70-75. 4. Naito E, Ito M, Takeda E, et al: Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia. Pediatr Res 1994;36:340-346. 5. Naito E, Ito M, Yokota I, et al: Molecular analysis of abnormal pyruvate dehydrogenase in two patients with thiamine-responsive congenital lactic acidemia. Muscle Nerve 1994;17(Suppl 1):128. 6. Robinson BH, MacMillan H, Petrova-Benedict R, et al: Variable clinical presentation in patients with defective E 1 component of pyruvate dehydrogenase complex. J Pediatr 1987;111:525-533. 7. Evans OB: Pyruvate decarboxylase deficiency in subacute necrotizing encephalomyelopathy. Arch Neurol 1981;38:515-519. 8. Federico A, Dotti MT, Fabrizi GM, et al: Congenital lactic acidosis due to a defect of pyruvate dehydrogenase complex (El). Eur Neurol 1990;30:123-127.