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.

Autopsy case of pure akinesia showing pallidonigro-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 pallidonigro-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 beta-amyloid were distributed in the thalamus.

[Autopsy findings of meningitis associated with multiple brain infarctions in two adult patients].

Cerebrovascular complications of meningitis have been extensively documented in the literature. It is little known, however, that paroxysmal, devastating, and potentially fatal complications can occur when the early signs of infection are subtle and missed. We describe the clinical course and neuropathological findings of the occurrence of brain infarctions during two atypical clinical courses of meningitis. In one patient, it was due to Serratia marcescens detected only by an autopsy specimen, and in the other, it was due to Aspergillus detected by a surgical biopsy. Death followed multiple, extensive, and progressively multiplicative infarctions in the basal ganglia, brainstem, and cerebral cortices. Autopsies revealed that the infarctions were caused by severe inflammatory change in the vascular walls, mainly of the arteries of the skull base, including the basilar and carotid arteries. Thrombus formation was also recognized in the lumen of several arteries. A number of characteristic Aspergillus hyphae were recognized in the arterial wall of one patient. Meningitis, which may be associated with severe vasculitis and lead to cerebral infarction, should be considered in the differential diagnosis of these conditions. Early diagnosis and initiation of vigorous therapy should be stressed for therapeutic success.

Immunohistochemical distribution of cation-dependent mannose 6-phosphate receptors in the mouse central nervous system: comparison with that of cation-independent mannose 6-phophate receptors.

Most mammalian cells express two types of mannose 6-phosphate (M6P) receptors (MPRs), which are involved in the sorting of lysosomal enzymes within the cells. They are referred to as cation-dependent (CD-) MPR and cation-independent (CI-) MPR/insulin-like growth factor II receptor (IGF-IIR), based on their divalent cation requirements and the ability to bind IGF-II. The complementary actions of these two related but distinct MPRs in the sorting function suggest that they have different immunohistochemical distributions. To address this issue, we investigated the cellular distribution of CD-MPR immunoreactivity in the adult mouse central nervous system (CNS), and compared it with that of CI-MPR/IGF-IIR immunoreactivity, which we had previously investigated. These two immunoreactivities were localized in neurons of the CNS, with more intense labeling in the medial septal nucleus, the nucleus of the Broca's diagonal band, layers IV-VI of the cerebral neocortex, layers II-III of the entorhinal cortex, the habenular nucleus, the median eminence, several nuclei and structures of the brainstem, the Purkinje cell layer of the cerebellum, and in the ventral horn of the spinal cord. Although intense immunoreactivities of both MPRs were observed in the same groups of neurons in the same regions, the spatial differences in immunoreactive intensity for CI-MPR/IGF-IIR were greater, particularly in the telencephalon such as the basal forebrain and cerebral cortex, than those for CD-MPR. These findings suggest that CD-MPR is ubiquitously necessary for the general function of neurons, whereas CI-MPR/IGF-IIR is selectively necessary for certain region- and neurotransmitter-specific functions of neurons.

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.

Primary squamous cell carcinoma of the brain. A rare autopsy case.

In the present study, a rare autopsy case of primary squamous cell carcinoma of the brain is described. The patient was a 49-year-old man who showed brainstem symptoms and signs. These included oculomotor, abducens and facial palsies, dysphagia, dysarthria, and long tract signs such as quadriplegia with Babinski's signs during the 3-year and 6-month course of his illness. Neuropathologically, poorly differentiated squamous cell carcinoma was seen in the pons, medulla oblongata, part of the midbrain and spinal cord, the base of the cerebellum, the hypothalamus, the optic chiasm, and the left parahippocampal gyrus. The base of the pons and medulla oblongata were extensively destroyed by tumor cells. The relevant literature regarding primary squamous cell carcinomas of the brain was reviewed, and the characteristic features of this rare condition were discussed.

[A case of chronic pure motor neuropathy associated with anti-GalNAc-GD1a-IgM antibody].

The patient was a 34-year-old male with chronic pure motor neuropathy with such acute onset as seen in Guillain-Barré syndrome. Neurological symptoms were gradually progressive for 4 weeks, and predominantly noted in the left side. Deep reflexes were normal and the distribution of muscle weakness was uneven. Plasma exchange reduced neurological symptoms. Four weeks later, right drop foot was relapsed. High dose intravenous immunoglobulin was effective. Serial electrophysiological studies indicated the asymmetric reduction of CMAP. Repeated assays of anti-GalNAc-GD1a IgM antibody were positive. This is the first report of chronic pure motor neuropathy as multiple mononeuritric type associated with anti-GalNAc-GD1a IgM antibody. This case adds to our knowledge better understanding of the pathogenetic role of anti-GalNAc-GD1a IgM antibody in inflammatory neuropathies.

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 Alzheimer's disease. The findings in our case suggested that aluminum alone might not develop Alzheimer's disease.

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 Sjögren's 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.

[A patient with muscular torticollis caused by nodular fasciitis in the sternocleidomastoid muscle (SCM)].

Nodular fasciitis is a benign pseudosarcomatous proliferative lesion which is frequently misdiagnosed as malignant tumor clinically and microscopically. It usually occurs as a rapidly enlarging subcutaneous mass on the upper extremities, especially on the forearm. Here we report a patient showing muscular torticollis caused by nodular fasciitis in the sternocleidomastoid muscle (SCM). A 17-year-old woman was hospitalized because of rapidly progressive torticollis. The right SCM was markedly enlarged and firm on palpation. Muscle biopsy taken from the right SCM revealed massive proliferation of spindle shaped fibroblasts infiltrating into the endomysium. These findings coincided with the intramuscular nodular fasciitis. However, different from typical nodular fasciitis, no apparent nodule formation was found in this patient. Instead, diffuse proliferative lesion extended widely into the neck soft tissue. To our knowledge, this is the first report of muscular torticollis caused by nodular fasciitis involving the SCM.

The reaction of glial progenitor cells in remyelination following ethidium bromide-induced demyelination in the mouse spinal cord.

The present study investigated how glial progenitor cells participated in the process of remyelination following ethidium bromide (EBr)-induced demyelination in the adult mouse spinal cord. In situ hybridization techniques for detecting mRNA for platelet-derived growth factor alpha receptor (PDGFalphaR) and proteolipid protein (PLP) were employed to identify glial progenitor cells and mature oligodendrocytes, respectively. During the demyelination stage and early stage of remyelination, large cells strongly expressing PDGFalphaR mRNA were observed in the border of the demyelinating lesion, and with immunohistochemistry they exhibited positive labeling of the astrocytic marker glial fibrillary acidic protein (GFAP). Other glial progenitor cells expressing PDGFalphaR mRNA proliferated around the lesion during the demyelination stage. During the remyelination stage, some PDGFalphaR mRNA-positive cells partly expressed mRNA for PLP in the periphery of the demyelinating lesion. These results suggest that PDGFalphaR mRNA-positive glial progenitor cells may give rise to both astrocytes and oligodendrocytes, which participate in remyelination following demyelination.