[Undifferentiated pleomorphic sarcoma in the left atrium; report of a case].

Primary cardiac sarcomas are rare. A 41-year-old woman complaining of dyspnea was admitted to our hospital. Echocardiography and computed tomography (CT) showed a primary cardiac tumor in the left atrium. During surgery, the tumor was noted to be arising from the anterior wall of the left atrium, under the aortic sinuses. Histological and immunohistochemical studies revealed an undifferentiated pleomorphic sarcoma. Eleven months later, echocardiography and CT showed recurrence of the cardiac sarcoma in the left atrium. The patient underwent wide resection of the left atrium and mitral valve replacement because the tumor extended to the mitral valve leaflet. The patient died 3 months after the 2nd surgery because of the 2nd recurrence of the cardiac sarcoma. Although most tumors that develop in the left atrium are benign myxomas, preoperative differential diagnosis is important. It is especially necessary to suspect a sarcoma in the case of a non-septal orgin of the mass.

[Intractable pneumothorax secondary to pulmonary metastasis of angiosarcoma].

A 68-year-old male suffered from right pneumothorax and was admitted to our hospital. He had a previous history of angiosarcoma of the scalp, and had received local resection and chemoradiotherapy. Chest computed tomography (CT) on admission revealed right pneumothorax and bilateral multiple thin-walled cavities of the lung. We performed partial resection of right lung. Histopathological examination showed a small metastatic lesion around the thin-walled cavities of the lung. Four months after the 1st lung resection, he suffered left pneumothorax. We performed partial resection of the left lung. Ten days after the 2nd lung resection, left pneumothorax recurred. Nine days later, he also developed right pneumothorax. We performed the 3rd operation for right lung. Thoracoscopy demonstrated multiple bullas in right lung and it showed impossibility for radical surgery. Although surgical resection for pneumothorax secondary to metastatic lung cancer is usually efficient, it is very hard to manage the pneumothorax of metastatic angiosarcoma.

Report of three cases of Alzheimer's disease with focal motor symptoms: clinical correlates of neuroimaging findings.

We report clinical and neuroimaging findings for three patients suffering from Alzheimer's disease (AD) with focal motor symptoms. These patients initially showed cognitive deficits and subsequently featured myoclonus and awkward movements in the unilateral upper limb while progressing to paresis. Paresis was noted in the unilateral upper limb. All patients held the unilateral arm flexed at the wrist and elbow, closely adducted to the body and the hand fisted and pronated. No signs of cerebellar ataxia, sensory disturbance or long tract signs were observed, nor any of the initial non-cognitive behavioural changes typical of frontotemporal dementia. EEGs of these patients showed marked slowing of basic activity without epileptic discharges. MRIs showed progressive brain atrophy in the contralateral frontoparietal lobes as well as the hippocampal formation. Cases 2 and 3 featured extensive long T2 lesions on MRI. 99mTc-HMPAO-SPECT revealed blood flow hypoperfusion in the corresponding regions. The cerebellum and brain stem showed neither morphological abnormalities nor blood flow hypoperfusion. On the basis of these clinical and neuroimaging observations, the focal motor symptoms were attributed to contralateral frontoparietal cortical atrophy with or without white matter lesion.

KP1 expression of ghost Pick bodies, amyloid P-positive astrocytes and selective nigral degeneration in early onset Picks disease.

We present a patient with early-onset Pick's disease in which selective nigral degeneration, KP1 expression of ghost Pick bodies and amyloid P-positive astrocytes were found. We also review the literature on early-onset Pick's disease. A 34-year-old man showed personality change including stereotypical behavior. Muscle rigidity and spasticity developed later, and he died twelve years after the onset of his illness. The brain showed lobar cerebral atrophy prominent in the temporal lobe, and to a lesser degree in the prefrontal and orbitofrontal cortex. The substantia nigra displayed profound degeneration whereas the head of the caudate nucleus and the putamen were not so seriously affected because the neurons were preserved and only slight astrocytic proliferation was seen. Many Pick bodies were found in the hippocampal formation, and ballooned neurons (Pick cells) were dispersed throughout the cerebral cortex, subcortical grey matter and hippocampal formation. The affected white matter exhibited severe fibrillary gliosis, and numerous astrocytes positive for glial fibrillary acidic protein and microglial cells positive for CR3/43 were found in the atrophied cortical lesions. The intraneuronal Pick bodies expressed ubiquitin, neurofilament and tau, and KP1 distinctly stained ghost Pick bodies. Tau-positive astrocytes were found in the striatum, hippocampal formation, pontine tegmentum, substantia nigra and affected frontotemporal cortices. These astrocytes were also positive for amyloid P. Extensive search of the literature on early-onset Pick's disease disclosed only a few cases with selective nigral degeneration, and we failed to find any differences in duration, progression of the illness and the extent of subcortical gray matter involvement between cases of early-onset and presenile onset of Pick' s disease. We conclude that the striatopallidal and nigral system can be affected independently in Pick's disease and report new immunohistochemical findings.

An autopsied case of Creutzfeldt-Jakob disease with the lateral geniculate body lesion showing antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses.

We reported an necropsy finding of a patient with Creutzfeldt-Jakob disease (CJD) who showed photo-stimulated giant spikes that simultaneously suppressed periodic synchronous discharges (PSD) and the loss of pupillary light reflex during the course of the illness. The necropsy revealed extensive gray and white matter lesions, and both the lateral geniculate body (LGB) and pregeniculate body were primarily affected. The superior colliculus, optic nerve and tracts were not affected. The cerebral cortices particularly of the occipital lobe were severely damaged. The Gennari line, however, was spared from lesion. The primary involvement of the LGB has been reported infrequently in CJD, however, it appears to be associated with the unusual electroencephalograph (EEG) feature of the present case. The pregeniculate lesion contributed to the loss of pupillary reflex. This finding indicates that the visual pathway may be involved in the mechanism of the generation of PSD in CJD.

Non-familial olivopontocerebellar atrophy combined with late onset Alzheimer's disease: a clinico-pathological case report.

A 76-year-old woman with olivopontocerebellar atrophy (OPCA) presented with progressive intellectual deterioration. She showed cerebellar ataxia and muscle atrophy and weakness, and gradually developed generalized dementia with visuospatial disturbance. An autopsy revealed numerous senile plaques (SPs), neurofibrillary tangles (NFTs) and neuropil threads particularly in the CA1, subiculum and entorhinal cortex and to a lesser degree in the cerebral neocortex shown by immunostaining and specific silver impregnation techniques. The nucleus basalis of Meynert had numerous NFTs with fibrillary gliosis and neuronal cell loss. The basis pontis was markedly atrophied and the pontine nucleus had severe neuronal depopulation and gliosis. The pontine transverse fibers were demyelinated with their axons being fragmented. The cerebellar white matter was also severely degenerated. The striatum, Onuf's and intermediolateral nuclei of the spinal cord remained unchanged. Ubiquitin immunohistochemistry and Gallyas silver impregnation technique revealed oligodendroglial inclusions in the pontine nucleus, corticopontine tract, cerebral and cerebellar white matter. On double immunostaining of KP1 and ubiquitin, globular neurite SPs encircled by KP1-positive fibrous structures were found in the hippocampus and cerebral neocortex. The curly neurite SPs contained KP1-positive granules. The KP1-positive microglial cells were distributed widely in the cerebral white matter and HLA-DR-positive ones were found around the SPs. The present case showed generalized dementia compatible with Alzheimer's disease (AD) and had a pathologically limbic type of late onset AD. This is the first case where AD affected non-familial OPCA.

KP-1 is a marker for extraneuronal neurofibrillary tangles and senile plaques in Alzheimer diseased brains.

KP-1 immunostaining with microwave pretreatment in formalin-fixed, paraffin-embedded sections enhanced its immunoreactivity revealing extraneuronal neurofibrillary tangles (NFTs) called ghost tangles, senile plaques (SPs) and perivascular deposits as well as microglial labelling in Alzheimer-diseased brains. KP-1 stained cored and uncored SPs, granules within the SPs, perivascular beta-amyloid protein (beta AP) and star-like beta AP deposits in cortical layer I, which was confirmed in comparison to silver-impregnated structures in the Reusche-stained or Gallyas-Schiff-stained sections. On double immunostaining with KP-1 and ubiquitin, ghost tangles were labelled by KP-1 and intraneuronal NFTs were positive for ubiquitin. A few KP-1-positive granules deposits different from amyloid core were found within the SPs and the outer margin of amyloid cores of SPs were stained by KP-1. KP-1-positive microglia were attached to the ubiquitin-positive intraneuronal NFTs. Microglia were more numerously labelled by CR3/43 than by KP-1, and CR3/43-positive microglia were found to be preferentially attached to SPs. As KP-1 recognizes lysosome-associated antigen CD68, similarities between KP-1 positivity and Reusche-stained structures suggested that lysosomal activity was associated with beta AP deposits and ghost tangles were involved in lysosome-associated processes. It is speculated that lysosomes play a role in the process of ghost tangle formation and in beta AP deposits leading to SP formation.

Borrelia burgdorferi-seropositive chronic encephalomyelopathy: Lyme neuroborreliosis? An autopsied report.

A 36-year-old Japanese woman presented with progressive cerebellar signs and mental deterioration of subacute course after her return from the USA. Her serum antibody to spirochete Borrelia burgdorferi was significantly elevated. A necropsy 4 years after her initial neurological signs revealed multifocal inflammatory change in the cerebral cortex, thalamus, superior colliculus, dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed spongiform change, neuronal cell loss, astrocytosis and proliferation of activated microglial cells. The internal capsule was partially vacuolated and the spinal cord, notably at the thoracic level, was demyelinated and cavitated in the lateral funiculus. Microglial cells aggregated within and around the spongiform lesions and microglial nodules were present in the medulla oblongata. Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus and inferior olivary nucleus showed the most advanced lesions with profound fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous thickening of the leptomeninges with lymphocyte infiltrates was localized in the basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus lesions and mental deterioration was attributable to the cortical and thalamic lesions. Spongiform change, neuronal cell loss, and microglial activation are characteristic pathological features in the present case. The cerebellar ataxia and subsequent mental deterioration are unusual clinical features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal inflammatory parenchymal change in the central nervous tissues and the present case may be an encephalitic form of Lyme neuroborreliosis.

[An autopsied case doubly infected by mucor mycelia and herpes simplex virus-2 in the remission state after bone marrow transplantation for acute myelogenous leukemia].

A 36-year-old woman who had been in complete remission after bone marrow transplantation against her leukemia presented with visual disturbance and cerebellar signs. She showed unusual involuntary movement as if she rolled a ball of string, and died two months after the onset of illness. Necropsy revealed hemorrhagic and necrotic lesions in the thalamus, basal ganglia, cerebellar dentate nucleus, superior colliculus, midbrain pretectum and red nucleus, and mucor mycelia were numerously found. HSV-2 immunoreactivity was found in both astroglial and oligodendroglial perikaraya. These hemorrhagic-necrotic lesions were partly associated with HSV-2 infection, but it was difficult to discriminate those from mucormycotic lesions. The unusual involuntary movement was considered to be due to basal ganglia lesions. This case was double infection by mucor mycelia and HSV 2, and clinicopathological consideration was described.

Non-Alzheimer dementia with status spongiosus and neuronal cell loss showing unusual perineuronal structures and point mutation at 129 codon of prion protein.

The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.

Striatonigral degeneration combined with olivopontocerebellar atrophy with subcortical dementia and hallucinatory state.

We present an autopsied case of striatonigral degeneration (SND) combined with olivopontocerebellar atrophy (OPCA) with subcortical dementia and hallucinatory state. A Japanese woman without a remarkable family history showed hand tremor at the age of 35 years, followed by bradykinesia, muscle rigidity, orthostatic hypotension, neurogenic bladder and pyramidal signs. No obvious cerebellar symptoms were found. Various antiparkinsonian drugs were administered, but were not markedly effective for the parkinsonism. She developed a mild dementia characterized by mild memory disturbance with preservation of orientation, slowing of thought processes, emotional lability toward sadness, impaired ability to manipulate acquired knowledge and poor calculating, and by the absence of aphasia, apraxia and agnosia. The features in this patient were consistent with those seen in subcortical dementia. She also had auditory hallucinations. MRI revealed hypointense T2 signals in the putamina and substantia nigra. T1-weighted MRI demonstrated atrophy of both the pons and cerebellum in addition to atrophy of the putamina and substantia nigra. EEG showed slowing of background activity. She died of cardiac failure at the age of 47. Autopsy disclosed brain stem tegmental atrophy, SND, OPCA and many glial cytoplasmic inclusions in the central nervous system, but well-preserved cerebrum. We discuss the relationship between the psychiatric symptoms and pathologic findings of brain stem tegmentum.

Age-related changes in nerve growth factor receptor immunoreactive neurons in the magnocellular basal forebrain system in rat brain--an immunocytochemical and morphometric study.

Morphometrical changes with aging in nerve growth factor receptor (NGFR) immunoreactive neurons in the basal forebrain were studied in juvenile and aged rat brains by means of NGFR immunohistochemistry. The nucleus basalis of Meynert (NBM) had cell loss and atrophy of NGFR immunoreactive neurons, and the horizontal nucleus of diagonal band of Broca (HNDB) showed only atrophy of these neurons. The medial septal nucleus and vertical nucleus of diagonal band of Broca had no significant change. Neuropil NGFR immunostaining was reduced in its intensity in the aged rats. As nerve growth factor is synthesized in the target areas and retrogradely transported to the nerve cell body within the basal forebrain and NGFR immunoreactive neurons are largely cholinergic ones, degeneration of NGFR-positive neurons in the basal forebrain may be related to a decreased cholinergic activity. The degeneration of the dendrites of NGFR-immunoreactive neurons were reported to be extensively found in the basal forebrain nuclei, in contrast, degeneration of the cell body of NGFR-immunoreactive neurons was confined to those in the NBM and HNDB in the present study. These findings suggest that atrophic changes in the dendrites precede those in the cell bodies of NGFR-immunoreactive neurons.

Ramsay Hunt syndrome: progressive mental deterioration in association with unusual cerebral white matter change.

An autopsied case of Ramsay Hunt syndrome with progressive dementia was reported. The clinical symptoms included progressive intellectual decline, myoclonus, generalized convulsive seizure, cerebellar ataxia and positive pyramidal signs. Neuropathological examination disclosed cerebral white matter demyelination marked in the frontal lobe and fibrillary gliosis predominantly in the subcortical U-fibers, grumose degeneration in the dentate nucleus and inferior olivary nucleus lesion. The skeletal muscle showed no ragged-red fiber. The present case can be included in Ramsay Hunt syndrome because of the absence of pathological hallmark of mitochondrial encephalomyopathy and of the presence of the degenerative lesions in the olivary and dentate nucleus without cerebellar Purkinje cell loss. The intellectual decline is a result of extensive frontal white matter change, and myoclonus and ataxia are closely associated with dentate grumose degeneration. The cerebral white matter change is an unusual finding and the present case might be a variant in Ramsay Hunt syndrome.

An autopsy case of tuberous sclerosis. Histological and immunohistochemical study.

We report an autopsy case of tuberous sclerosis. A 19-year-old Japanese man had shown facial adenoma sebaceum, intractable convulsive seizures and severe mental retardation. Gross inspection of the brain showed a cortical tuber from the orbital frontal lobe to the rhinencephalon of the left side and a few subependymal nodules. Histological examination revealed many cortical tubers in the cerebral hemispheres, a few subependymal nodules with calcification and multifocal clusters of heterotopic cells in the white matter (white matter nodules). In these lesions, massive giant cells with abundant eosinophilic cytoplasm and without Nissl substances were found. Although the size and shape of the giant cells were variable, the majority of them were gemistcytic, ovoid or polygonal. Immunohistochemistry was employed in these lesions using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), vimentin (VM) and myelin basic protein (MBP). In the cortical tuber, the majority of the giant cells were positive for both NFP and VM, but a few were positive for GFAP. All of them were negative for MBP. In the subependymal nodule and white matter nodule, the majority of the giant cells were positive for NFP, but a few were positive for VM, and none were positive for either GFAP and MBP. These findings suggest that the majority of the giant cells may be immature cells toward neuronal series and a few may be those toward astroglial series. These findings also indicate that the giant cells in the subependymal nodule and white matter nodule may be more differentiated than those in the cortical tuber. The nature of the giant cells in tuberous sclerosis is discussed.

Gallyas-Schiff stain for senile plaques.

Gallyas technique was modified by a direct application of Schiff's reagent after physical development, resulting in distinctive staining of amyloid deposits in argyrophilic structures. With this modified method, senile plaques in Alzheimer's disease are clearer. This method is easy to perform and suitable for routine neuropathological examination.

Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy--an immunocytochemical and Gallyas silver impregnation study.

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.

[Cytoskeletal proteins abnormalities in olivopontocerebellar atrophy].

A highly sensitive silver technique for glial cytoplasmic inclusions in olivopontocerebellar atrophy (OPCA) was applied to 15 subjects with neurodegenerative disorders including 4 patients with OPCA, 4 patients with Joseph disease and with 3 normal control subjects, and the argyrophilic structures in the OPCA cases were immunocytochemically examined. As a result, the argyrophilic structures were found in the OPCA cases and Alzheimer cases. The argyrophilic structures included the white matter oligodendroglia, and neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus. The pontocerebellar tracts and the surrounding white matter of the inferior olivary nucleus contained a small number of argyrophilic nerve fibers with a hollow structure, which were interpreted as myelin. Immunocytochemistry demonstrated that the oligodendroglia in the white matter had immunoreactivities to an paired helical filament (PHF), microtubule associated protein 5 (MAP5), tau and ubiquitin antiserum, and the astroglia in the white matters had an immunoreactivity to a MAP5 antiserum. In the putamen, pontine nucleus and inferior olivary nucleus, in addition to the immunoreactivities observed in the oligodendroglia, the neurons were immunoreactive for PHF, MAP5, tau and ubiquitin antisera, and the astroglia had the same immunoreactivities as the neurons except for being tau negative in the putamen. The nerve fibers in the pontocerebellar tract and inferior olivary nucleus capsule were strongly positive for myelin basic protein and negative for PHF antiserum. These findings indicate that the Gallyas positive argyrophilia in the OPCA subjects is closely associated with PHF or tau.