Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

OBJECTIVE: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. METHODS: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month (8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI (within 1 week in eight patients). CONCLUSION: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats.

Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain after hypoxic-ischemic (HI) insult. Caspase inhibitors have been developed as antiapoptotic agents. Hippocampal damage after HI insult is strongly related to tissue temperature, and systemic hypothermia has been introduced clinically for brain protection. In this study, we examined the effects of a caspase inhibitor and systemic hypothermia on neuronal protection in the developing rat brain. Postnatal d 7 rat pups were subjected to the Rice model of hypoxia for 1 h. Systemic hypothermia was induced with a water bath at 29 degrees C. Before HI insult, a pan-caspase inhibitor, boc-aspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the cerebral ventricle. The ipsilateral hippocampus was subjected to caspase assays and histologic assessment. The HI group at 37 degrees C (HI-37 degrees C) showed a peak of caspase-3 activity 16 h after insult. This activity was significantly reduced in the presence of BAF or hypothermia (HI-29 degrees C group, p < 0.05) or by the combination of HI-29 degrees C + BAF (p < 0.01 versus HI-37 degrees C). The number of neuronal cells in the ipsilateral hippocampal CA1 region in the HI-37 degrees C group was significantly decreased (62.9% versus control). The number of neuronal cells was maintained in the HI-37 degrees C + BAF group (82.7%), the HI-29 degrees C group (78.7%), and the combination group (95.2%) (p < 0.05 versus HI-37 degrees C). A combination of systemic hypothermia and BAF produced a strong protective effect against neuronal damage in the developing rat brain, along with a reduction in caspase-3 activity.

Expression of protective protein in human tissue.

The authors investigated by immunohistochemistry the distribution of protective protein in human tissues. Immunoreactivity was observed in the cytoplasm, revealing a granular pattern and cell type specificity. The most intense staining was observed in the large neurons of brain, distal and collecting tubular cells of kidney, epithelial cells of bronchus, and Leydig cells of testis. In a patient with galactosialidosis type IIa, all these stains were absent. The neurons that were most strongly stained in the control group, such as the Betz cells, neurons in the basal forebrain, motor neurons in the cranial nerve nuclei, and ventral horn cells of the spinal cord, were markedly ballooned in the patient with galactosialidosis.

Peroxisomal bifunctional enzyme deficiency: serial neurophysiological examinations of a case.

We report on a case of 21-month-old girl with peroxisomal bifunctional enzyme deficiency, which was diagnosed by means of complementation analysis. Serial neurophysiological examinations were also carried out. The motor and sensory nerve conduction velocities of the median nerve showed lower borderline values at 3 months of age and were within range at 11 months of age. Later, those velocities gradually decreased. The electrically elicited blink reflex at 3 months of age showed the prolongation of latencies of R1, R2 and R2' and the interpeak latencies of R1-R2 and R1-R2'. Furthermore, R1, R2 and R2' showed prolonged latencies at 11 months of age and were absent at 15 months of age. The auditory brainstem response (ABR) showed, bilaterally, normal latency of wave I, prolonged interpeak latencies of waves I-V. At 11 months of age, waves III and IV-V of ABR were detected, but their amplitude was very low. At the age of 15 months ABR was absent. These results and the following report are valuable for understanding the pathogenesis of neurological symptoms.

Immunochemical and immunohistochemical localization of Bcl-x protein in the rat central nervous system.

To explore the role of bcl-x in the regulation of cell death in the nervous system, we produced monoclonal antibodies against rat Bcl-xL protein, the major product of the rat bcl-x gene that inhibits apoptosis, and defined its distribution in rat neural tissues by immunochemical and immunohistochemical means. Western blotting of tissue homogenates identified the Bcl-x protein as two bands with molecular weights of about 29 and 31 kDa. The level of Bcl-x expression in the nervous system was high, being comparable to that in the hematolymphoid system, and higher in the fetal than in the adult brain. Subcellular fractionation studies localized Bcl-x to various subcellular compartments. In tissue culture, Bcl-x was produced by all the cell types examined, including neurons, astrocytes, oligodendrocytes and microglial cells. Immunohistochemistry revealed that Bcl-x immunoreactivity was more intense in the gray than in the white matter. In the fetal cerebral cortex, labeling was mostly confined to the neuronal perikarya, whereas in the more mature brain, the neuropil of the gray matter, as well as the glial cells in the white matter, was also stained.

High expression of Bcl-x protein in the developing human cerebellar cortex.

The gene bcl-x, which is related to a bcl-2, regulates programmed cell death. bcl-x may function in the development of the nervous system. We raised a polyclonal antibody against human Bcl-x protein, and investigated its distribution in the developing human cerebellum. Western blotting revealed that Bcl-x expression in the cerebellum is higher in the fetal, than in the postnatal period. Immunohistochemical studies of fetal brains localized intense Bcl-x immunoreactivity in the granule cell processes at 13-22 gestational weeks and in the Purkinje cell bodies at 24-38 weeks. The immunoreactivity decreased after birth, but was retained in the Purkinje cells at a low level until adulthood. These results suggested that Bcl-x expression in the cerebellum is developmentally regulated and involved specifically in the development of neuronal subpopulations.

Difficulties of families with handicapped children after the Hanshin-Awaji earthquake.

In order to clarify the difficulties which handicapped people experienced in the Hanshin-Awaji earthquake disaster, 678 families with handicapped children were studied 1.5 months after the earthquake. All the students who were enrolled in this study were going to some type of school or training classes for handicapped children in January 1995. The study was completed between 1 and 10 March. The questionnaires which were designed for this study consisted of three parts: the difficulties which the families were faced with, their requirements for social and medical services and the symptoms and reactions of their children after the earthquake. A total of 466 answers were obtained from their parents. The kinds of difficulties differed between the families of mentally retarded children and those of the physically handicapped. While many parents with physically handicapped children desired better medical information or materials, many parents with mentally retarded children wanted better care services for their children. Physical and psychological effects of the earthquake were only temporary in most cases. However, some of the handicapped children were still suffering from such reactions as of 10 March. From the results of our study it became evident that a systematic relief program for these handicapped people should be established. The relief program should include the distribution of information regarding medical and social services. Psychological reactions such as panic, excitement and suppression of mental activity were still observed in some handicapped children on 10 March. Further observation will therefore be necessary.

Development of endothelial nitric oxide synthase in endothelial cells in the human cerebrum.

We demonstrate the distribution and development of endothelial nitric oxide synthase (eNOS) immunoreactivity in vessels of the human brain. eNOS-positive endothelial cells were recognized in small vessels in the parenchyma of the cerebrum, as well as in the large arteries and veins in the leptomeninges. By 10-13 weeks of gestation, eNOS-positive endothelial cells had already appeared in the vessels of the leptomeninges and deep white matter. Immunoreactivity for eNOS was noted in most vessels at 14-17 weeks in the intermediate white matter, at 18-21 weeks in the cortex, and at 23-26 weeks in the subcortical white matter. Such differences in regional development may be responsible in part for the topographical predilection for hemorrhagic or hypoxic-ischemic lesions in the developing brain.

Developmental immunohistochemistry of the 22 kDa peroxisomal membrane protein in the human brain.

We studied immunohistochemically the 22 kDa peroxisomal membrane protein (PMP 22). In the control brain, the immunopositive neurons for PMP 22 appeared 2-3 weeks earlier than those for peroxisomal enzymes. PMP 22-immunopositive glial cells appeared at 26-27 gestational weeks, increased with gestational age, and were rarely recognized after 1 year of age. In the patients with Zellweger syndrome, PMP 22-immunoreactivity was recognized in neurons, glias, liver and kidney cells.

The prenatal age critical for the development of the pontosubicular necrosis.

Pontosubicular neuronal necrosis is characterized by neuronal karyorrhexis, showing a peculiar distribution. In infants delivered at more than 29 gestational weeks (GW), neuronal karyorrhexis is restricted to the pons and subiculum, while in very premature infants (delivered at less than 28 GW), neurons in other brain regions, such as the inferior olivary nucleus, cerebellum, basal ganglia, thalamus and cerebral cortex, are also involved. Thus, karyorrhexis is more widely distributed in the more immature brain, implicating neuronal maturation as one of the pathogenetic factors relevant to this type of neuronal cell death.