[A case of motor neuron disease with presenile dementia showing bilateral degeneration of the pyramidal tract on cranial MRI].

A 58-year-old man developed dysarthria followed by a personality change. Subsequently, he developed muscle weakness and atrophy of the left upper and lower limbs, leading to repeated falls when he tried to walk. Neurological examination showed mild dementia, dysarthria, dysphagia, atrophy and fasciculation of the tongue, and muscle weakness and atrophy of all four extremities, particularly on the left side. Deep tendon reflexes were slightly diminished in the upper limbs and slightly exaggerated in the lower limbs without Babinski's sign. Cranial MRI revealed marked atrophy of the medial portions of the temporal lobes, more striking on the right, and T2-weighted imaging revealed symmetrical high-intensity signals from the posterior limbs of the internal capsules to the cerebral peduncles in the midbrain, extending to the pons on the left. 125I-IMP SPECT showed diffuse reduction of RI uptake in the frontal and temporal lobes, which was more marked on the right. We diagnosed this is a case of motor neuron disease with presenile dementia, which Mitsuyama et al. proposed as a new clinical entity, as well as a rare example of bilateral degeneration of the pyramidal tract on cranial MRI.

Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system.

Although brain lesions have been described in some cases with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the nature of brain lesion and its relation to the spinal cord lesion. In the present study, we performed histopathological analysis of the brain and the spinal cord of four autopsied cases with HAM/TSP to clarify the relationship between the brain and the spinal cord lesions. In two cases with active-chronic inflammation in the spinal cord, perivascular inflammatory infiltration was also seen in the brain, and the composition of cell subsets was similar both in the spinal cord and in the brain. No active inflammatory change was seen in the brain in two cases with inactive-chronic spinal cord lesions. Inflamed vessels were distributed mainly in the deep white matter and in the area between cerebral cortex and white matter of the brain. In the spinal cord inflamed vessels were mainly seen in the bilateral lateral and the ventral posterior columns. Parenchymal infiltration was diffused in the spinal cord but very sparse in the brain, suggesting the importance of parenchymal infiltration in the destruction of tissues. These results suggest that inflammatory changes occurred simultaneously in the spinal cord and in the brain, and that distribution of inflamed vessels closely correlated with the characteristics of vascular architecture of the brain and the spinal cord, which lead to a slow blood flow. This study may help promote a better understanding of the pathogenesis of HAM/TSP.

[A familial case of spinocerebellar ataxia type 8 (SCA 8)--its clinical findings and an issue about the genetic basis].

We report a 28-year-old woman with spinocerebellar ataxia type 8 (SCA 8). This patient began to exhibit dysarthria at the age of 19. At the age of 25, she fell and hit her head while drunk and then a neurosurgeon found that her cerebellum was atrophic on cranial CT and MRI. Neurological examination on admission to our hospital revealed ataxic speech, limb ataxia and mild hyperreflexia without Babinski's sign. Cranial MRI showed only mild atrophy of the cerebellar hemispheres and vermis. Based on the results of genetic analysis, which showed expanded CTG repeats[(CTA) 13 (CTG) 5 (CCG) 4 (CTG) 124] on the SCA 8 locus at 13q21, she was diagnosed as having SCA 8. As clinical signs of SCA 8, Koob et al. reported limb spasticity and diminished vibration perception including cerebellar ataxia. Furthermore, Hirose et al. and Satoh et al. reported cases showing involuntary movements such as myoclonus or chorea including cerebellar ataxia. Our case and Ikeda's cases presented a pure cerebellar phenotype. We think that SCA 8 exhibits clinical heterogeneity. On the other hand, Stevanin et al. and Worth et al. expressed doubt as to whether the SCA 8 locus at 13q21 is the gene actually responsible for autosomal dominant cerebellar ataxia (ADCA). We conclude that it is necessary to accumulate additional case reports, and to further investigate the relationship between the clinical findings and the results of genetic analysis in order to determine whether or not the SCA 8 locus at 13q21 is the genetic basis for ADCA.

[A study of clinical symptoms, muscle pathology, therapeutic response, and prognosis of myositis in patients with HTLV-1 associated myelopathy (HAM)].

Myositis is one of well-known complications of HTLV-1 associated myelopathy (HAM). On twelve HAM patients, 10 women and 2 men complicated with myositis, we examined their clinical symptoms, muscle pathology, and therapeutic response. Clinical examination revealed gait disturbance in 10, weakness of upper limbs in 6, muscle atrophy in 4, and myalgia in 3 patients. Blood test disclosed elevated serum CK level in 6 patients. Muscle biopsy showed marked inflammatory changes with many necrotic and degenerating fibers in 7 patients, and the rest showed only focal invasion of inflammatory cells. Eight patients received corticosteroid or immunosuppressant therapy. The neurological symptoms were improved in 5 of 8 patients 3 months after the treatment. And only one out of 5 patients whom we followed up 3 years after the treatment showed improvement.

[A family with probable autosomal dominant bulbospinal muscular atrophy with gynecomastia].

We reported a 52-year-old man and his family with bulbospinal muscle atrophy (BSMA) and gynecomastia. The propositus presented with the clinical picture of late onset progressive bulbospinal muscular atrophy including postural tremor, general hyporeflexia, mild maturity onset diabetes, gynecomastia and sexual impotence. One of his brother and his two sons had gynecomastia. His elder son had ocular movement abnormality, associated movement of facial muscle and finger tremor. One of his brothers showed tongue fasciculation without gynecomastia. None of members examined had abnormal expansion of CAG repeats in the androgen receptor gene. We speculate that this family has a new clinical entity characterized by bulbospinal muscular atrophy with an autosomal dominant inheritance.

[A case of thoracic extradural spinal cord teratoma with neurological sequelae more than 10 years after surgery].

We describe a rare case of a 42-year-old man with extradural spinal cord teratoma who presented with left Brown-Séquard syndrome more than 10 years after surgery for a left posterior mediastinal tumor. When he was 29 years old, he underwent an operation for a posterior mediastinal tumor. Histological findings showed adenocarcinoma in teratoma. Ten years after the operation, the patient developed left leg weakness. Three years later, he developed superficial sensory disturbance in his right leg. MRI showed extradural tumor formation at the level of the Th 9 vertebra, which compressed the spinal cord from the left posterior side. At surgery, the tumor was well encapsulated and extended to the left posterior side of the spinal cord through the intervertebral foramen. The histological findings were almost identical to those from the mediastinal tumor. This dumbbell tumor apparently developed from the remainder of the posterior mediastinal tumor over a period of more than 10 years.

[Two cases of POEMS syndrome with increased vascular endothelial growth factor (VEGF)].

We report a greatly increased amount of vascular endothelial growth factor (VEGF) in sera of two cases with POEMS syndrome. They had solitary myelomas in the cervical (case 1) and lumbar vertebrae (case 2). In both cases, serum VEGF decreased after steroid therapy. Sural nerve biopsy in case 1 showed marked subperineurial edema. The pathomechanism of polyneuropathy in POEMS syndrome may be due to involvement of the blood-nerve barrier by way of increased microvascular permeability induced by VEGF. VEGF is therefore not only a useful diagnostic marker for POEMS syndrome, but may also be a marker of clinical improvement.

[A case of Kennedy-Alter-Sung (KAS) syndrome presenting as hypersexuality and elevated serum CK: usefulness of genetic analysis].

We report a unique case of KAS syndrome presenting as hypersexuality and elevated serum creatine kinase (CK). None of the other members of the patient's family had KAS. The patient had engaged in sexual behavior 4 approximately 5 times a week since his marriage. He did not have gynecomastia or hepatomegaly. Neurological examination revealed facial twitching and tongue atrophy and fasciculations. Mild to moderate muscular atrophy and weakness were evident in the proximal portion of the upper and the distal portion of the lower extremities. Deep tendon reflexes were absent, as were sensory disturbance and sphincter dysfunction. Laboratory data showed mild elevation of transaminase (GOT 113 U/L, GPT 69 U/L) and extreme elevation of CK (4,600 U/L) in serum. Electromyography and muscle biopsy from the left biceps showed chronic neurogenic atrophy. Genetic analysis showed increased expansion of a CAG repeat (44 repeats) in exon 1 of the androgen receptor gene. We diagnosed KAS syndrome based on the genetic analysis. This case is important in illustrating the clinical varieties of KAS syndrome, as well as the importance of genetic analysis in KAS syndrome cases presenting with atypical manifestations and without a family history.

Familial spastic paraplegia with mental impairment and thin corpus callosum.

We described four patients in two families of unique familial spastic paraplegia (FSP) which was thought to be possibly autosomal recessive inheritance. All four patients had quite similar manifestations. Gait disturbance started at their second decade, then spastic paraparesis and mental deterioration progressed slowly. Cerebellar ataxia and sensory loss in the distal parts of four extremities were also slightly presented. In all patients, cranial MRI revealed marked thin corpus callosum with mild changes in the region of periventricular white matter and in the gray matter. Biopsied sural nerves of all patients showed chronic axonal degeneration with mild decrease of both large and small myelinated fibers. Electron microscopic study demonstrated crystalline-like inclusion bodies in the cytoplasm of Schwann cells in all patients. Despite extensive investigation for metabolic disorder, we could not find any abnormality. However an etiology have not established at the time presented, the combination of these clinical features suggested that the disorder could represent a specific clinical entity.

[A case of radiation neuropathy following radiation therapy for metastasis of breast cancer].

We report a 49-year-old woman with radiation neuropathy, which occurred 7 years after radiation therapy for supraclavicular lymph node metastasis of breast cancer. The patient had noticed a hard induration in the right breast twelve years previously and had a radical operation for right breast cancer. After surgery, she remained well until 7 years ago when she noted a right supraclavicular mass. Based on a diagnosis of metastasis of breast cancer at the right supraclavicular lymph node, she received radiation therapy at 50 Gy in 25 fractions to the lesion. Seven years after radiation therapy, the patient noted muscle weakness of II-V fingers of the right hand, followed by muscle atrophy of the right forearm. We diagnosed her condition as radiation neuropathy based on the absence of a mass lesion in the right supraclavicular region, no RI deposits in that region on Ga and bone scintigraphy, findings supportive of a lesion in the right brachial plexus on EMG and the history of radiation therapy for supraclavicular lymph node metastasis of breast cancer 7 years previously. We treated the patient with pulse therapy with high-dose oral prednisolone. Subsequently, the muscle weakness and atrophy of the right forearm and fingers have improved gradually. We suggest that pulse therapy with high-dose oral prednisolone for radiation neuropathy should be evaluated in a clinical trial, since few therapies are available for this condition.

Low levels of serum apolipoprotein A I and A II in senile dementia.

We studied the serum lipoprotein and apolipoprotein profiles in 44 patients with sporadic late-onset Alzheimer's dementia and 43 patients with vascular dementia. The levels of high-density lipoprotein (HDL) cholesterol were lower in both patient groups than in a control group. Apolipoprotein A I and A II levels have decreased in both the patient groups, especially in the vascular dementia group. The HDL-cholesterol levels correlated positively with the level of apolipoprotein A I, but not with the level of apolipoprotein A II. The ratios of apolipoprotein A I/A II have increased in both the patient groups. The apolipoprotein A II levels have disproportionally decreased in the patient groups. The serum apolipoprotein A II may involve the pathological process in the patients with senile dementia.

[A case of herpes zoster meningoencephalitis followed by involvement of cranial nerves IX, X, XI].

The patient is a 64-year-old woman with herpes zoster meningo-encephalitis followed by involvement of cranial nerves IX, X, XI. On admission, she had severe neck pain on the left side and mild nuchal rigidity. Three days later, herpetic vesicles on the left side of her neck (C2, C3, area). Herpes zoster meningoencephalitis was diagnosed based on CSF pleocytosis, high serum and CSF titers of herpes zoster antibody, and EEG abnormality. During hospitalization, paralysis of the left vocal cord, rightward deviation of the uvula, and gradual paralysis of the left sternocleidomastoideus and trapezius muscles developed. On cranial magnetic resonance imaging (MRI), T2-weighted image clearly revealed a high-signal lesion in left dorsal part of the medulla oblongata. This area appeared to correspond to the nucleus ambiguous and vagal nucleus. In this case, we believe that the inflammation originated in the C2, C3 posterior ganglion cells, extended to the IX, X, XI cranial nerves and to the part of the medulla oblongata. It is likely that the number of patients in whom a lesion of the cranial nucleus is revealed by MRI will increase in the future.

[A family case of HAM and HTLV-I carrier including two sisters presenting with myositis].

We reported a family case of HAM and HTLV-I carrier including two sisters presenting with myositis. Both the 65-year-old elder sister and her 53-year-old younger sister initially noted lumbago and developed difficulty in walking several years later. Neurologic examination revealed muscle weakness of the proximal parts of the upper and lower limbs (especially the latter). Mild hyperreflexia in all extremities, urinary disturbance and constipation were detected in the elder sister, while only urinary disturbance and constipation were seen in the younger. Anti-HTLV-I antibody in both serum and CSF was positive in both sisters. Muscle biopsy specimens showed features of myositis with perivascular, perimysial and endomysial lymphocyte infiltration. Although an association between HTLV-I and polymyositis had not yet been established, we think that our cases support such an association.

[Juvenile Binswanger-type encephalopathy with alopecia and spondylosis deformans--a case report].

The patient is a 33-year-old male and his parents are first cousins. He noticed his hair loss since about the age 14. At age 29, he manifested gait disturbance and urinary incontinence, which gradually progressed. Neurologically, he showed dementia (WAIS < 64), pyramidal and extrapyramidal signs, and pseudobulbar palsy. His blood pressure was normal. He also had dry skin with sclerema and marked cervical and lumbar spondylosis. His brain CT showed enlargement of the lateral ventricles and the periventricular low density areas. T2 weighted image of MRI showed diffuse high intensity in the periventricular white matter. Yamada et al presented a case progressive subcortical vascular encephalopathy (Binswanger type) with alopecia and spondylosis as a possible new syndrome, and this patient has the same syndrome. The etiology of this syndrome has not been known at the present time. The biopsied skin from the patient showed much hyaline deposits like glycoprotein in perivascular area of dermis. These morphological changes are very similar to those of lipoid proteinosis. These findings suggested that the pathological mechanism of this syndrome might be related to the biochemical disturbance in lipoid proteinosis.

[Serum lipids, lipoproteins and apolipoproteins in patients with senile dementia].

Serum lipid, lipoprotein, apolipoprotein, and sterol profiles were studied in 22 patients with senile dementia of the Alzheimer type (SDAT) and 29 patients with vascular dementia (VD). Levels of high density lipoprotein-cholesterol (HDL-C) were lower in both patients groups of SDAT and VD than in control group. Apolipoprotein AI and AII are two major proteins in HDL. In this study, apolipoprotein AI levels were normal, but apolipoprotein AII levels were lower in the patient groups, especially in the VD group, than in the control group. Lipoprotein(a) levels were higher in both patient groups, especially in the VD group. There were no differences of cholesterol, cholesterol precursors (desmosterol and lathosterol), and plant sterols (campesterol and beta-sitosterol) among the three groups. Murine apolipoprotein AII is a serum precursor of murine senile amyloid protein, and the apolipoprotein AII variant with proline-->glutamine substitution at position 5 in the serum of accelerated senescence-prone mice is identical to the murine senile amyloid fibril protein from amyloid-deposited tissues of these mice. In human SDAT and VD, the reason for the low level of apolipoprotein AII remains unclear.

Cerebrotendinous xanthomatosis: cranial CT and MRI studies in eight patients.

We report the findings on cranial computed tomography (CT) and magnetic resonance imaging (MRI) and their correlation with the clinical manifestations, disease severity and biochemical abnormalities in eight patients with cerebrotendinous xanthomatosis. CT revealed cerebral atrophy in seven cases, cerebellar atrophy in four and focal low density lesions in the cerebral white matter in two. T2-weighted MRI showed high signal lesions in the cerebral white matter, focal in four cases and diffuse in one, and in the globus pallidus in three patients, two of whom also had lesions in the cerebellar white matter. While severely affected patients showed variable CT and MRI abnormalities, our cases did not show the dramatic findings expected from the neurological manifestations. Diffuse lesions in the cerebral and cerebellar white matter have been emphasized in previous reports, but in our study the focal lesions in the cerebral white matter were also present; the globus pallidus was frequently involved.

[Clinical and epidemiological studies on inpatients with dementia].

We have studied 97 patients with dementia who have been discharged from our hospital and 106 inpatients with dementia who have been admitted during last two years in our hospital. The diagnosis of dementia was done according to the criteria of DSM-III. Based on their clinical course, neurological signs, Hachinski's ischemic score and neuroradiological findings, we divided patients into 4 groups, [senile dementia of the Alzheimer type (SDAT), vascular dementia (VD), unclassified dementia and other dementias which includes dementia with Parkinson's disease or motor neuron disease, etc.]. Concerning 70 demented patients who died during hospitalization, the average age of onset and the duration of illness of SDAT were 80.5 years old and 4.6 years respectively and those of VD were 77.6 years old and 2.7 years respectively. The common causes of death were pneumonia (50%) and cardiac failure (24%). Recurrence of cerebral vascular accident (CVA) was also another frequent cause of death in VD. The most common behavioral problems causing admission in patients of SDAT were aimless wandering, nocturnal delirium, illusion and hallucination. In VD, nocturnal delirium, aimless wandering, violence and abnormal monologue were most common causes of admission. The important causes degrading ADL of inpatients were fracture, especially fracture of the hip joint, pneumonia, intestinal bleeding and CVA. Concerning the increase of the population of over 75 years old, it will be suggested that the care and treatment of demented patients in this age group will become a major social problem.