Toshisaburo Nagai

Mitochondrial tRNAlle mutation in fatal cardiomyopathy

A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.

Divergent projections of catecholamine neurons of the locus coeruleus as revealed by fluorescent retrograde double labeling technique

Divergent projections of catecholamine (CA) neurons of the locus coeruleus have been studied by fluorescent retrograde double labeling in conjunction with monoamine histofluorescence technique. The present results indicate that the coerulo-cortical CA system is composed of two types of neurons. A predominant type possesses few divergent axons innervating a restricted region, while the other type projects widely to various areas of the cerebral cortex. The existence of divergent axonal projections of single CA neurons in the locus coeruleus to the cerebellum and the spinal cord, to the frontal cortex and the cerebellum, is also demonstrated.

Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy

Using magnetic resonance (MR) diffusion-weighted method, we examined the optic and the trigeminal nerves of jimpy and twitcher mice, considered to be animal models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe disease, demyelination disorder, respectively. In jimpy mice, diffusional anisotropy of optic nerve did not show a significant difference compared to age-matched control mice, suggesting that diffusional anisotropy does exist in absence of multiple layers of myelin sheath. In twitcher mice, diffusional anisotropy was attenuated remarkably in the optic and trigeminal nerves. Loss of axonal straightness on longitudinal section confirmed by electron microscopy appeared to be the principal explanation for it. It is further suggested that this MR diffusion-weighted imaging method enables us to differentiate hypomyelination from demyelination in vivo.

Perfusion-fixation of the human brain for immunohistochemistry: comparison with immersion-fixation.

A method of perfusion-fixation of the human brain is described and compared with immersion-fixation by immunoperoxidase staining for several substances (tyrosine hydroxylase, substance P, choline acetyltransferase, glutamate decarboxylase, Met-enkephalin, and neuron-specific enolase) in human striatum. Results from 1-cm slices fixed by immersion for 1, 2, 4 and 8 days were compared with results from slices of perfused brain postfixed for the same time periods. The fixative used in all steps was 4% paraformaldehyde at 4 degrees C. In the immersion-fixed brains, optimal immunoreaction for tyrosine hydroxylase and glutamate decarboxylase was limited to a depth of 1-2 mm from the surface of the brain slice. In contrast, staining density in perfusion-fixed brains was relatively homogeneous and of high quality. The other antigens studied displayed more uniform staining throughout the section with both perfused and immersed brains. Investigators intending to study human brain immunohistochemistry using immersion-fixation should be aware of the possibility of depth-related variations in staining intensity and would be wise to determine whether this effect is significant for the antigens they choose to study.

Manganese Deposition in the Brain During Long-Term Total Parenteral Nutrition

BACKGROUND Manganese deposition was suspected in a pediatric patient who received long-term total parenteral nutrition. T1-weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations. METHODS Whole-blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese. RESULTS The whole-blood manganese level during supplementation was 135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/L after a manganese-free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1-weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized. CONCLUSIONS It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole-blood manganese level, which was associated with the abnormal high intensity lesions on T1-weighted magnetic resonance images.

Coronary diameter in normal infants, children and patients with Kawasaki disease

Background : The coronary assessments in Kawasaki disease are mainly based on the Japanese Ministry of Health and Welfare criteria, which is simply classified according to the patient’s age, over 5 years and less than 4‐years‐old.

Microangioarchitecture of rat parietal cortex with special reference to vascular "sphincters". Scanning electron microscopic and dark field microscopic study.

Microangioarchitecture of the rat parietal cortex was studied by means of scanning electron microscopy and dark field microscopy. The richest supply of blood vessels in the parietal cortex was found in layer HI + IV and layer V, where 2 isolated plexuses of microressels were prominent. Tbe appearance of the plexuses was quite different between motor and sensory areas. In the motor area the capillary plexuses were narrow and compact, while in sensory area the plexuses were wide and diffuse. Characteristic ring formations, called ring-shaped-compressions in the present study, were frequently observed at branching sites of arterioles. The ring-shaped-compression probably corresponds to the precapillary sphincter. A similar structure was also seen in capillaries and venules and, therefore, it is likely that not only arterioles, but also capillaries and eren venules, can actively change diameter to control cerebral blood flow.

Zonisamide Monotherapy in Newly Diagnosed Infantile Spasms

Summary: Purpose: We determined the short‐term efficacy of zonisamide (ZNS) monotherapy in newly diagnosed patients with infantile spasms (IS).

Distribution of nitric oxide synthase in the central nervous system of Macaca fuscata : subcortical regions

The distribution of nitric oxide synthase-immunoreactive neurons was studied in the Macaca fuscata by immunohistochemistry using antiserum against nitric oxide synthase. In the macaque lower brainstem, many nitric oxide synthase-containing cell bodies were found in the gigantocellular and parvocellular reticular nuclei, the nucleus of the spinal tract of trigeminal nerve, the cochlear nucleus, the prepositus hypoglossi and the nucleus of the solitary tract. Many nitric oxide synthase-immunoreactive perikarya were observed in the laterodorsal-pedunculopontine tegmental nucleus complex of the macaque pontine and midbrain tegmentum. In addition, there were many highly immunoreactive cell bodies in the superficial layers of the inferior and superior colliculi. In the forebrain, numerous cell bodies were observed in the caudate nucleus, putamen, nucleus accumbens, nucleus of the diagonal band, anterior perforated substance and amygdaloid complex. Whereas most of these neurons were labeled highly intense for nitric oxide synthase, there were also many lightly labeled nitric oxide synthase-immunoreactive neurons in the substantia innominata, globus pallidus, ansa peduncularis and lateral hypothalamic nucleus. The present observation indicated some species difference in the distribution of central nitric oxide synthase-containing neurons. Furthermore, the present neuroanatomical evidence that nitric oxide synthase is distributed in a variety of specific neuronal systems, with some differences in the patterns of cytoplasmic localization, further indicates the neural messenger role of nitric oxide in the central nervous system.

Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome) – A nationwide questionnaire survey in Japan

UNLABELLED The aim of this study was to establish strategies for prophylaxis against status epilepticus (SE) associated with high fever and for management of ongoing SE in children with severe myoclonic epilepsy in infancy (SMEI). METHODS The investigation was performed retrospectively using a questionnaire, asking about medications, which was distributed to epilepsy specialists throughout Japan. All respondents were members of the Japan Epilepsy Society (JES) and/or the Japanese Society of Child Neurology (JSCN). Data from 109 SMEI patients (51 males and 58 females), 1-37 (M+/-SD, 10.7+/-6.53) years old, were used for this study. Of these 109 patients, 10 were excluded because they had not experienced SE, such that data from 99 patients were analyzed. RESULTS Among the anti-epileptic drugs (AEDs) used daily, excellent efficacy against SE evolution was obtained with the following: potassium bromide (KBr) (41.7%), zonisamide (ZNS) (13.5%), clobazam (CLB) (10.0%), valproate (VPA) (8.0%), phenobarbital (PB) (6.7%), and phenytoin (PHT) (2.6%). Excellent efficacy was not obtained with either clonazepam (CZP) or carbamazepine (CBZ). The diazepam (DZP) suppository was the most frequently given drug for prophylaxis against SE triggered by fever, but only 2 (2.4%) cases showed excellent results. Excellent efficacy in terminating ongoing SE was obtained with the following medications; intravenous barbiturates (75-100%), intravenous midazolam (MDZ) (68.8%), intravenous DZP (54.3%), intravenous lidocaine (Lid) (21.4%), and intravenous PHT (15.4%). CONCLUSIONS Daily KBr was most efficacious for controlling seizures in SMEI patients. Early use of intravenous barbiturates is the most effective strategy in stopping SE in a subset of patients. Reliable efficacy in SE was not obtained with prophylactic DZP, intravenous benzodiazepines (BZPs), PHT and Lid.