Teruo Shirabe

Mitochondrial encephalomyopathy (MELAS): pathological study and successful therapy with coenzyme Q10 and idebenone.

Two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS) in one family are reported. Pathological examination of case 1 showed ragged-red fibers, with 7% of the fibers being unstained by cytochrome c oxidase stain, peripheral nerve damage, multiple areas of softening in the cerebrum and midbrain, and spongy changes in the cerebrum, optic nerve and pons. Electron microscopic examination revealed abnormal accumulations of mitochondria in the skeletal muscle, smooth muscle and cardiac muscle. The activity of cytochrome c oxidase in the brain and liver showed a tendency to decrease. In case 2 (maternal aunt of case 1), muscular weakness and peripheral nerve damage improved by treatment with coenzyme Q10. By adding idebenone to the coenzyme Q10 therapy, the EEG and Wechslers Adult Intelligence Scale (WAIS) improved. Furthermore, in the cerebral spinal fluid (CSF), the protein, lactate, and pyruvate decreased, and the monoamines and monoamine metabolites increased.

Epstein-Barr virus-associated post-transplant primary smooth muscle tumor of the liver: report of an autopsy case.

Epstein‐Barr (EB) virus‐associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus‐associated smooth muscle cell tumor in a 21 year old female who received immunosuppres‐sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α‐smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus‐encoded RNA 1 (EBER‐1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo‐grafts, but also in those with renal allografts.

Autopsy case of aluminum encephalopathy.

We report the case of a 59‐year‐old female aluminum encephalopathy patient who had chronic renal failure and took 3.0 g hydroxy‐aluminum gel per day for the control of serum phosphorus level during a 15‐year period. Nine months before her death she developed disorientation, memory disturbance, emotional incontinence, general convulsions and consciousness disturbance. Neuropathologically, the brain showed nerve cell atrophy and mild loss with stromal spongiosis, proliferation of astrocytes and microglia in the cerebral cortex, basal ganglia and thalamus. Some nerve cells were stained immunohistochemically by phosphorylated neurofilament, but apparent neurofibrillary tangles were not observed. Aluminum was detected in the nerve cells of the cerebral cortex by X‐ray microanalysis. Despite the long‐term intake of aluminum, there were no neuropathological findings of Alzheimers disease. The findings in our case suggested that aluminum alone might not develop Alzheimers disease.

Peripheral myelin protein 22 is expressed in human central nervous system.

We studied the expression of peripheral myelin protein 22 (PMP22) gene in the human central nervous system (CNS). Northern blot analysis was performed with polyA+ RNA blots containing several parts of the human brain and the spinal cord using human PMP22 cDNA as a probe. As two alternative PMP22 transcripts have been reported and since exon 1A-containing transcripts are associated with myelin formation, the exon 1A fragment was also used to examine this transcript. Total PMP22 mRNA was significantly detected in most parts of brain and spinal cord, while exon 1A-containing transcripts were detected in the medulla, spinal cord and corpus callosum. PMP22-like immunoreactivity was identified in motor neurons and preganglionic sympathetic neurons in the spinal cord. PMP22 was also detected in pia mater of the spinal cord. These results suggest that PMP22 might play an important role in human CNS.

An autopsy case of amebic meningoencephalitis. The first Japanese case caused by Balamuthia mandrillaris

We report here the first case of amebic meningoencephalitis caused by Balamuthia mandrillaris in a 78‐year‐old Japanese woman with Sjögrens syndrome. Fourteen days before her death, she presented with high fever and lost consciousness and later developed neck stiffness and abducens palsy. Computed tomography scans of the brain demonstrated multiple low‐density areas throughout the brain. Neuropathologically, hemorrhagic and necrotic lesions with many amebic trophozoites were scattered in the brain and spinal cord. Granulomatous lesions were only rarely found. The amebas were identified as Balamuthia mandrillaris based on immunofluorescence assay. Clinicopathologically, our case was thought to be an intermediate between primary amebic meningoencephalitis due to Negleria fowleri and granulomatous amebic encephalitis due to Acanthameba species. Essentially, the case was one of an elderly person with suspected immunodeficiency with fulminant necrotic meningoencephalitis and scanty granulomatous lesions of 14 days course.

Expression of insulin-like growth factors in remyelination following ethidium bromide-induced demyelination in the mouse spinal cord

Insulin‐like growth factors, IGF‐I and IGF‐II, play important roles in development and myelination in the CNS, but little is known about the response of IGF after demyelination. The present study investigated the expression of IGF and their cognitive receptors in the process of remyelination following ethidium bromide (EBr)‐induced demyelination in the adult mouse spinal cord. The present results, in a quantitative real‐time PCR, showed significant increases in the levels of the mRNA for both IGF‐I and IGF‐II during both the demyelination and remyelination stages. The levels of IGF‐I receptor (IGF‐IR) mRNA increased from 10 days to 4 weeks after the EBr injection. The levels of IGF‐II receptor (IGF‐IIR) mRNA decreased for 6 days and then increased 10 days after the EBr injection. In situ hybridization studies showed the cells expressing IGF‐I mRNA to be mainly macrophage‐like cells, while those expressing IGF‐II mRNA were predominantly Schwann cell‐like cells invading the demyelinating lesion. The immunoreactivity for the IGF‐IR and IGF‐IIR increased in various kinds of cells within and around the demyelinating lesions from 6 days to 4 weeks after the EBr injection. These results suggest that locally produced IGF could partly be involved in some mechanisms underlying remyelination processes following the EBr‐induced demyelination in the mouse spinal cord.

Subcortical vascular encephalopathy in a normotensive young adult with premature baldness and spondylitis deformans a clinicopathological study and review of the literature

Progressive subcortical vascular encephalopathy (PSVE) usually occurs in elderly individuals, suffering from hypertension. We here describe a male, born of consanguineous parents, who first showed signs of PSVE at the age of 30. Despite the absence of hypertension or known metabolic causes, the degenerative cerebral vascular disease developed progressively. Several cases, surprisingly identical to the one reported here, were traced using Japanese medical records. They are clinically characterized by: early onset of PSVE (at age 25-30), absence of persistent hypertension, diffuse alopecia since youth, spondylitis deformans with early onset, often so severe as to necessitate surgery, and the possible existence of an autosomal recessive transmission. Cases with these features appear to constitute a distinct clinical entity, possibly a new form of premature aging syndrome.

Autopsy case of pure akinesia showing pallido‐nigro‐luysian atrophy

A 60‐year‐old man developed levodopa‐resistant pure akinesia. The patient gradually became more akinetic without accompanying gaze palsies, nuchal dystonia, or other parkinsonian features such as rigidity or tremor. At the age of 71, he died of bronchopneumonia. Neuropathologically, bilateral marked neuronal loss and gliosis were restrictedly observed in the globus pallidus, substantia nigra and corpus luysii, whereas mild gliosis without neuronal loss was found in the brain stem. With Gallyas‐Braak silver stain, numerous argyrophilic fibrous structures partly surrounding glial nuclei were observed in the three major affected regions. With Bodian stain, however, they were rarely recognized. The structures were partly positive for tau protein. Rare neurofibrillary tangles were found in the three areas and brain stem. They were relatively more numerous but still sparse in the hippocampus and the parahippocampus. The present case was diagnosed as having pallido‐nigro‐luysian atrophy based on two characteristic findings: (i) the distribution of lesions showing neuronal loss with gliosis; and (ii) significant presence of tau‐positive argyrophilic fibrous structures related to glia but with the absence of neurofibrillary tangles in the major affected regions and the brain stem. As our present case uniquely showed pure akinesia for the whole clinical course, it is noteworthy to report it here with a full neuropathological evaluation. In addition, a moderate number of diffuse plaques positive for β‐amyloid were distributed in the thalamus.

X-ray microanalytical studies of lead-implanted rat brains.

SummaryVarious cytoplasmic and intranuclear inclusions found in macrophages and astrocytes of lead-implanted rat brains were studied with an energy dispersive x-ray microanalytical technique. Cytoplasmic inclusions contained large quantities of lead, calcium and phosphorus. The proportions of these elements were different within each inclusion. Intranuclear inclusions also contained small amounts of lead and, occasionally, calcium.

DISSEMINATED TRICHOSPORON BEIGELII INFECTION IN A PATIENT WITH MALIGNANT HISTIOCYTOSIS

A case of disseminated Trichosporon beigelii infection is reported. Trichosporon inhabits the soil, but may also be present in the human skin and mouth as a normal flora. Occasionally it causes superficial mycotic infection, but it is rarely invasive. A review of literature disclosed 21 reported cases of invasive Trichosporon beigelii infection, to date. Of these, two cases were from Japan. The scarcity of reports on this invasive infection may be due to a lack of awareness of the organism. Histologically, it should be carefully differentiated from Candida.