Biomedical subjects

Y Morimatsu

Publications and source records attributed to Y Morimatsu.

At least 19 recordsLinked to original sources

PubMed2004

Hereditary paroxysmal ataxia with mental retardation: a clinicopathological study in relation to episodic ataxia type 2.

A case of hereditary acetazolamide-responsive paroxysmal ataxia with mild mental retardation in an autopsied Japanese man is described. His ataxic attacks had occurred for approximately 65 years since the age of 6. One of his daughters had severe mental retardation and epilepsy, and the other had paroxysmal ataxic attacks and mild mental retardation. Analysis of the subject's CACNA1A gene and that in his daughter revealed neither mutations nor CAG expansion. Neuropathologically, cortical degeneration consisting of the marked loss of Purkinje and granule cells was found exclusively in the cerebellar vermis. This was consistent with findings at autopsy for cases reported as spinocerebellar ataxia 6. In addition, there were minor anomalies, such as hypoplastic cerebellum and brainstem, heterotopic Purkinje cells, and cortical microdysgenesis of the temporal lobe. It is considered that the cerebellar cortical degeneration and the minor malformations found in the brain are closely related to one another, rather than having occurred independently.

Adult↗

PubMed2001

Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease: a report of an autopsy case with a clinical course of 15 years.

This report concerns an autopsy case of atypical amyotrophic lateral sclerosis (ALS) with dementia mimicking frontal Pick's disease. The patient was a Japanese woman without hereditary burden who was 45 years old at the time of death. She developed abnormal behavior and amnesia at age 30, followed by disinhibition, aspontaneity, urinary incontinence, abulia, and rectal incontinence. Neurological signs compatible with ALS developed about 14 years after the disease onset. No respirator was used throughout the clinical course. Macroscopically, neuropathological examination showed atrophy of the frontotemporal lobes with accentuation in the convexities of the frontal lobes. Histologically, there was neuronal loss in the cerebral cortex, parahippocampal gyrus, amygdala, caudate nucleus, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to marked degeneration of the pyramidal tracts. Ubiquitin-immunoreactive neuronal inclusions were present in the frontotemporal cortical layer II neurons and motor neurons in the brain stem and spinal cord. In the hippocampal dentate granular cells, many ubiquitin-immunoreactive neurites were present without ubiquitin-immunoreactive intraneuronal inclusions. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS with dementia of long disease duration. We also note the possibility that motor neuron disease-inclusion dementia with a long clinical course may develop into ALS in the final stage of the illness.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Neurodegenerative features in developmental brain disorders.

The authors examined the occurrence of neurofibrillary tangles (NFT), senile plaques, spheroids in Goll's nucleus, grumose or foamy spheroid bodies (GFSB) in the basal ganglia, and hyaline inclusions in the brainstem nuclei in 62 patients under 40 years of age with non-progressive developmental brain disorders. Five cases had demonstrated NFT, which tended to be confined to the subcortical nuclei, whereas no senile plaques were identified in any case. Spheroids in Goll's nucleus were significantly increased in three cases of congenital brain anomalies and five cases of perinatal hypoxic ischemic encephalopathy. The GFSB-positive subjects were clinicopathologically divided into two subgroups consisting of four cases of congenital malformations, which were also associated with severe respiratory failure, and six cases of perinatal brain disorders in which the basal ganglia were severely affected. Eosinophilic intracytoplasmic inclusions, unlike the hyaline inclusions of the Lewy type, were found in the substantia nigra and/or locus ceruleus in two subjects. It is speculated that a variety of mechanisms, including accelerated aging and anoxic insults, may be involved in the increased occurrence of NFT and/or spheroids in non-progressive developmental disorders. A detailed investigation is useful to clarify the neuronal changes secondary to the brain damages early in development.

Adolescent↗

PubMed2001

Oxidative stress and disturbed glutamate transport in hereditary nucleotide repair disorders.

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each of XPA, CS, and control groups. All oxidative products, including nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE) were deposited in large amounts in the globus pallidus of CS patients compared to XPA patients. They were frequently recognized in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of HNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA patients. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They were also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may be involved in pallidal and/or cerebellar degeneration in hereditary nucleotide repair disorders.

ATP-Binding Cassette Transporters↗

PubMed2000

Cerebellar degeneration in hereditary dentatorubral-pallidoluysian atrophy and Machado-Joseph disease.

We examined the mechanism of cerebellar degeneration in brains obtained at autopsy from six cases of hereditary dentatorubral-pallidoluysian atrophy (DRPLA) and six cases of Machado-Joseph disease (MJD), using terminal deoxynucleotidyltransferase-mediated in situ nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins, neurotrophin receptors and glutamate transporters. In three subjects with DRPLA, who developed dementia and cerebellar ataxia at over 50 years of age, the number of Purkinje cells was mildly reduced, TUNEL-positive cells were observed in the molecular layer of the cerebellar cortex, and immunoreactivities for calbindin D28K and excitatory amino acid transporter-1 (EAAT1) were altered in the molecular layer. In addition, all cases of DRPLA showed a reduction of immunoreactivity for EAAT1 in the dentate nucleus. In MJD, augmentation of Bcl-x expression by the Purkinje cells, and increases in Trk B- and GFAP-immunopositive glial cells in the granular layer were observed in half of the cases, whereas immunoreactivity for EAAT-1 was preserved both in the cerebellar cortex and dentate nucleus. One case of MJD showed TUNEL-positive granular cells in the cerebellar cortex. Age-matched control subjects did not show TUNEL-positive cells or immunohistochemical changes in the cerebellum. There were neither TUNEL-positive cells nor alteration of the in situ expression of apoptosis-related proteins in the dentate nucleus in either variant of hereditary spinocerebellar degeneration, although both exhibited grumose degeneration in the dentate nucleus. These findings indicate that latent degeneration in the cerebellar cortex may occur in DRPLA and MJD, in addition to the dentate change, which is the cardinal feature in the neuropathology of these two diseases. The lesion of Purkinje cells and their processes in the molecular layer associated with altered glutamate transport may be important in DRPLA, while the significance of the abnormalities observed in some MJD cases, which might be related to apoptotic mechanism, remains unclear.

ATP-Binding Cassette Transporters↗

PubMed2000

Immunohistochemical analysis of brainstem lesions in infantile spasms.

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.

Adolescent↗

PubMed1999

Immunohistochemical evaluation of the marbled state in childhood hypoxic encephalopathy.

We have immunohistochemically analyzed the marbled state in 8 cases of perinatal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic encephalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillary acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synaptophysin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. The abnormally myelinated fibers in the marbled state were stained with both Kluver-Barrera and Holzer stainings; however, they were partly immunopositive for MBP and completely immunonegative for GFAP, CaBD, MEnk, PV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities for those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or anti-NF immunostainings in the cerebral cortex and striatum but not in the thalamus. GFAP-positive astrocytes did not show any continuity with the abnormally myelinated fibers. These histological features were seen in the cerebral cortex, striatum and thalamus. Difference of the etiology did not affect the histological features with the exception of anti-PV staining, in which PV-immunopositive neurons were observed only in aged subjects with infantile hypoxic encephalopathy, and seemed to be more severely affected by hypoxic stress during the perinatal period than the early infantile period. These data suggest that the site of lesion or the length of survival period after brain injury might influence the formation of the marbled state rather than the etiology. And the direct relationship between the abnormally myelinated fiber and astrocytic process was not verified.

Adolescent↗

PubMed1999

Pathological study on sibling autopsy cases of the late infantile form of neuronal ceroid lipofuscinosis.

We report autopsy cases of two brothers with the late infantile form of neuronal ceroid lipofuscinosis (LINCL) and examine apoptotic cell death in autopsied brains. Both patients showed psychomotor developmental delay, cerebellar ataxia, convulsions, visual disturbance and myoclonus, and they became bedridden around the age of 6-7 years. Macular changes, mimicking cherry-red spots, were observed on funduscopy, but conjunctival biopsy failed to disclose storage materials. In these cases, the autopsies demonstrated severe atrophy with neuronal loss and gliosis throughout the brain and spinal cord, except the hypothalamic neurons and motor neurons in the brain-stem and spinal cord, and autofluorescent lipofuscin-like materials of two types, fine granular deposits and coarse round bodies, were stored in the remaining neurons and glial cells, and in the epithelial cells of various visceral organs. Immunostaining for mitochondrial subunit C visualized the fine granular deposits but not the coarse round bodies. The nuclei of neurons and glia cells were stained by in situ nick end labeling, which was more pronounced in the younger case, although the expression of both bcl-2 and bcl-x was not significantly altered in these cases. It is suggested that immunohistochemistry for subunit C may be useful for diagnosis of NCL, and further investigations are necessary to clarify the relationship between LINCL and apoptosis, especially in severely affected cases.

Atrophy↗

PubMed1999

Neurodegeneration in hereditary nucleotide repair disorders.

Both xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are rare autosomal disorders, have a genetic defect in the step of nucleotide repair, and involve various neurological abnormalities caused by progressive neurodegeneration. We performed comprehensive neuropathological analysis of five cases of XPA and four cases of CS. The XPA cases showed widespread neuronal loss throughout the central nervous system, in sharp contrast to the comparative preservation of neurons in the CS cases, who rather exhibited patchy demyelination in the cerebral and cerebellar white matter, and multifocal calcium deposition in the basal ganglia and cerebral white matter, respectively. Exceptionally in the cerebellar cortex, neuronal loss was more severe in CS than in XPA. Grumose or foamy spheroid bodies occurred in the globus pallidus and substantia nigra, and axonal torpedoes were increased in the cerebellar cortex in both disorders. Neither silver impregnation nor immunohistochemistry for ubiquitin or tau succeeded in visualizing neurofibrillary tangles, senile plaques or augmented ubiquitination in either disorder, and these findings did not support the involvement of facilitated aging in the neurodegeneration in XPA or CS.

Adolescent↗

PubMed1999

[Public health nurses' disaster responses for intractable neurological patients at home].

OBJECTIVE: This paper describes the 1995 Hanshin-Awaji Earthquake experience of the local public health nurses. The purpose of the study was to identify problems regarding assistance of intractable neurological patients at home during and after the earthquake and to discuss ways to improve future local disaster responses by public health nurses for those patients. METHODS: Approximately 2 hours of a group interview of public health nurses from 2 public health centers in Kobe City was conducted in August, 1996. Interview data was collected via audio-tape and transcribed. The data was organized according to phases of the earthquake. The acute phase of the earthquake disaster ended within 72 hours. The data was then analyzed to identify problems in assisting intractable neurological home patients in order to discuss disaster responses by public health nurses. RESULTS: There was a delay in confirming the safety of and providing needed assistance for intractable neurological patients at home by public health nurses. During the first 3 days after the earthquake, the majority of public health nurses were unable to commute to work due to the shutdown of transportation systems. In addition, nurses, who were able to come to work, were preoccupied with treating earthquake casualties and distributing medical supplies. Other factors associated with the delay included the following: lack of a registration list for intractable neurological patients at home; lack of close contacts between public health nurses and patients, and between public health nurses and patient support groups; and sparing nurses for guiding volunteers and for coordinating between shelters and hospitals. CONCLUSION: Measures to improve future disaster responses are as follows: a) teaching patients and their families how to safeguard against disaster; b) preparing registration lists; c) establishing support networks and cooperating with network members; and d) upon disaster, assigning some nurses to assess the needs of patients.

Disaster Planning↗

PubMed1998

Cerebellar neurodegeneration in human hereditary DNA repair disorders.

Recent findings have focused attention on the role of apoptosis in neurodegenerative diseases, however, the apoptotic process in child-onset brain disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are hereditary disorders characterized by impaired DNA repair and neurodegeneration. We investigated apoptotic cell death in the cerebellum of five cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT-mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in the granule cells of the cerebellar cortex of two patients with XPA and two patients with CS, whereas such cells were not detected in the cerebellar cortex in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression was not altered. Some patients showed nuclear expression of p53 in the granule cells and/or molecular layer, bax-positive glial cells in the cerebellar white matter, and a few Trk B-positive cells in the granular layer. These findings suggest that apoptotic cell death can be involved in the cerebellar degeneration in patients with hereditary defects in DNA repair mechanisms.

Adolescent↗

PubMed1998

Megalencephaly, hydrocephalus and cortical dysplasia in severe dwarfism mimicking leprechaunism.

This report concerns an autopsy case of megalencephaly exhibiting a unique combination of physical and brain malformations. A 4-year-old boy had a peculiar face, a severe reduction of subcutaneous adipose tissue, severe growth failure and frequent hypoglycemic episodes. These clinical features were compatible with leprechaunism; however, the absence of hyperinsulinemia and insulin resistance prevented the diagnosis of leprechaunism. The autopsy disclosed complex cardiac and brain malformations. Although hydrocephalus coexisted, the brain weight after complete removal of the cerebrospinal fluid was 2260 g, which was greater than the average brain weight of normal Japanese children of the same age. The neuronal density in the cerebral cortex was decreased, while the surface area of the cerebral cortex and white matter were greater than those in an age-matched control. There was cortical dysplasia in the frontal and parietal lobes. Endocrine tests and immunohistochemical analysis of the brain did not demonstrate any abnormalities in the hypothalamus-pituitary system. Megalencephaly can be associated with dwarfism, and this case is important for consideration of the interrelationship between neuronal proliferation and physical growth.

Brain↗

PubMed1997

Neuropathology of the dentate nucleus in developmental disorders.

The dentate nucleus was examined histologically and immunohistochemically in 47 cases of nonprogressive developmental disorders. Neuronal loss and/or atrophy was observed in 13 cases, while mild neuronal lesions, characterized by dendritic swelling and/or the appearance of eosinophilic materials around the neurons, were exhibited in 20 cases. The former change was accompanied by diffuse central nervous system involvement, and the etiology was perinatal hypoxic ischemic encephalopathy, acute encephalopathy, and meningoencephalitis in most cases. On the other hand, most of the patients with kernicterus showed the latter change. Immunohistochemically, the mild neuronal lesions mimicking grumose, degeneration, described in some neurodegenerative diseases, seemed to reflect the changes of Purkinje cell terminals. It is suggested that secondary structural alteration of the dentate neurons in the absence of severe atrophy can occur in nonprogressive developmental disorders.

Adolescent↗

PubMed1997

[Cortical status marmoratus in a patient with a sequela of postnatal anoxic encephalopathy].

Status marmoratus (ST) of the basal ganglia and thalamus has been observed in cases of perinatal hypoxic ischemic encephalopathy and rarely of postnatal encephalopathy. In occasional cases, the cerebral cortex is also involved. Here, we reported a 22-year-old male with a sequela of postnatal anoxic encephalopathy. He had been bedridden with severe mental retardation since he suffered anoxic encephalopathy at 3 months of age. ST was found in the cerebral cortex as well as basal ganglia and thalamus. In addition to ST, the cerebral cortex and white matter were remarkably devastated. We also performed a preliminary immunohistochemical study to investigate the process of ST formation, using antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and synaptophysin. MBP-positive abnormal myelinated fibers were identified in the ST areas, which were not colocalized with GFAP-immunopositivity. Synaptophysin was positive in the areas of ST, which were not stained with Holzer method. These results suggest that the myelination in the early infancy damage of basal ganglia and cerebral cortex could be implicated in the formation of ST.

Adult↗

PubMed1997

[Localized lesions on MRI in the globus pallidus, subthalamic nuclei and hippocampus in patients with severe intellectual and motor disabilities].

We examined the clinical picture of eight patients with severe intellectual and motor disabilities, who had experienced prolonged and severe neonatal jaundice, and showed localized lesions in the globus pallidus, subthalamic nuclei and hippocampus on MRI. All patients had athetoid tetraplegia, and five patients showed disturbed ocular movements and seven showed dysphagia. Five patients could communicate with others or utter words, and all showed mental retardation. Auditory brainstem responses were abnormal in seven, and the percentage of REM sleep on all-night polysomnography was reduced in three. Neither CT nor T1-weighted MR images could detect any changes in the pallidum or subthalamic nuclei, while T2-weighted MR images disclosed bilateral high signals in the pallidum, especially in the internal segment, in all patients. Five of the 7 patients, in whom coronal T2-weighted MR imagings were obtained, showed high signals in the subthalamic nuclei. The hippocampus showed atrophy and/or T2-prolongation in seven patients. In one autopsy case, these MRI changes were concordant with pathological lesions. In patients with athetoid cerebral palsy, brainstem dysfunctions, and abnormal ABR, localization of MRI lesions to the pallidum and subthalamic nuclei is evidence for neonatal bilirubin encephalopathy.

Adult↗

PubMed1996

Collagen-encapsulated coagulation necrosis in cerebral infarcts: a pathological study.

Coagulation necrosis (CN)--a type of necrosis characterized by firm, eosinophilic parenchyma with recognizable cell outlines--is thought to be a result of rapid degeneration of tissue protein to a gel state and loss of water which prevents the necrotic tissue from undergoing autolysis and cellular digestion. In this study, we observed CN in cerebral infarcts of 11 of 150 consecutive autopsy cases of large cerebral infarction. Cerebral CN in patients who had survived for about 1 month had already started to be surrounded by newly formed vessels and type I collagen-positive tissue. In patients who had survived for more than 1 year, CN was deposited with calcium and cholesterin crystals and encapsulated by thick, dense collagenous tissue. Encapsulation, however, was not always complete, a finding that suggests that other factors, such as gel transformation at an early stage of CN and calcification at a later stage, are important for the persistence of CN in the infarct. The results of our study suggest that cerebral CN occurs more frequently than is generally believed.

Aged↗

PubMed1996

Septo-optic dysplasia with cerebellar hypoplasia in Cornelia de Lange syndrome.

Little is known about the neuropathology of Cornelia de Lange syndrome. We report a unique type of cerebral malformation combined with Cornelia de Lange syndrome in a 5-year-old female child. At autopsy, the optic systems, hypothalamic nuclei, corpus callosum and cerebellar vermis were hypoplastic, and the septum pellucidum, fornix and anterior commissure were rudimentary. The brain had malformative features of septo-optic dysplasia combined with commissural dysplasia and cerebellar vermian hypoplasia. This case suggests an interrelationship between Cornelia de Lange syndrome and midline development of the brain.

Brain↗

PubMed1994

A neuropathological study of a case of lupus erythematosus with chorea.

Neuropathological examination in a 48-year-women of SLE with chorea was performed. Histological examination of the putamen showed a widespread neuronal loss associated with reactive astrocyte proliferation and neuropil rarefaction at both sides. Disappearance of large neurons was more prominent than that of small ones. Although a few old and fresh microinfarcts were scattered in the same area, there was no significant pathological abnormality in small vessels. The caudate nuclei also showed a few irregular microinfarcts and spotty loss of neurons associated with reactive astrocytosis. These neuropathological changes might be related to the appearance of choreatic movement in patients with SLE.

Astrocytes↗