Showing papers in "Rinshō shinkeigaku Clinical neurology in 1995"

Thalamic experiential hallucinosis

Abstract: Two patients with an infarct limited to the thalamus developed auditory and visual experiential hallucinations. Neuropathological studies in one patient showed a small cavity in the right intralaminar nuclei surrounded by focal spongiform change, partly involving the right dorsomedial nucleus. Neuroradiological data in another patient indicated that the same nuclei in the left thalamus were also affected. It was concluded that a unilateral thalamic lesion could cause experiential hallucinations and the intralaminar and dorsomedial nuclei might be important structures to explain the phenomenon.

[Epidemiology of syringomyelia in Japan--the nationwide survey].

Abstract: The nationwide epidemiological survey of syringomyelia was carried out in Japan by sending inquiries to neurologists, child neurologists, neurosurgeons and orthopedic surgeons for the period of 1991 and 1992. A total of 1,243 cases of syringomyelia were ascertained. Among them, 622 were men and 619 women, and the average age of onset was 28 years old. The classification by Barnett et al was used, presenting syringomyelia with Chiari malformation in 684 cases (51.2%), dysraphism in 47 (3.7%), post traumatic syringomyelia in 139 (11%), post-spinal arachnoiditis in 76 (6%), spinal cord tumor in 132 (10.5%) and others in 204. Its predominant clinical course was slowly progressive, but 202 cases (17.9%) showed rather stable course including spontaneous resolution in 29 cases. The main initial symptoms were numbness in 522 cases (42%), motor disturbance in 504 (40.5%), and pain in 296 (23.8%). Neurologic signs noted in the abnormality of deep tendon reflexes in 836 cases (67.3%), motor disturbance in 763 (60.4%) and positive pathological reflexes in 383 (30.1%). Sensory disturbance was found in 942 cases (75.8%) and the dissociated type were 559 out of them (59.3%). It is noteworthy that 982 out of 1,243 were documented by MRI and surgical operations such as foramen magnum decompression, syringo-subarachnoid shunt and others were performed in 829 cases. Syringobulbia was confirmed on MRI in 101 cases of syringomyelia in which spinal cord tumors were most frequently associated.

Severe childhood autosomal recessive muscular dystrophy

Abstract: Dystrophin is associated with several novel sarcolemmal proteins via the cysteine-rich/C-terminal domains. The dystrophin-associated proteins are classified into three groups: (1) alpha- and beta-dystroglycan, (2) adhalin, 35DAG and A3b, and (3) members of the syntrophin family. Dystrophin interacts with F-actin via the N-terminal domain. Alpha-dystroglycan binds laminin-2, a major component of the basal lamina. These findings indicate that the dystrophin-glycoprotein complex (DGC) links the subsarcolemmal cytoskeleton with the basal lamina, thus providing mechanical stability to the sarcolemmal. The DGC may also play a role in signal transduction. We have reported previously the deficiency of adhalin in skeletal muscle of Arab patients afflicted with severe childhood autosomal recessive muscular dystrophy (SCARMD). SCARMD is now known to affect other races including Europeans and Japanese. Although the phenotype of this disease can mimic Duchenne muscular dystrophy in severe cases, it is sometimes quite mild. SCARMD is genetically heterogeneous. Recently, adhalin gene mutations have been demonstrated in European, Arab and Japanese families with SCARMD. Another locus is on chromosome 13q, however, the mutated gene remains elusive. In the advanced stages of SCARMD, the expression of laminin is disturbed, suggesting that adhalin deficiency may cause the dysfunction of the DGC as a laminin receptor, which may eventually lead to muscle cell death.

[Disappearance of ALS from Guam: implications for exogenous causes]

Abstract: The author reports the disappearance of amyotrophic lateral sclerosis (ALS) from Guam over past 30 years, which coincided with rapid changes in the ecology, socioeconomy, and westernization of the life style. This slow but steady decline is believed to be the consequences of radical changes from food collection to wage-based life style and dietary improvement in recent years and elimination of exogenous factors. Those risk factor(s) are believed to be the environmental trace metals which must have triggered the accelerated oxidative stresses in the motor neurons of genetically susceptible population. Changing Epidermiology: 1. The annual incidence of 70/100,000 in 1960s down to 7/100,000 in 1990s, and remained unchanged for past 15 years. 2. Upward shift of age at onset by 10 years and at death by 8 years and even out of sex ratio. 3. Birth cohort analysis showed less risks for those born after 1920. No ALS cases born after 1945. 4. No increase in the incidence of ALS among non-Chamorros transients of Guam and Marianas during W.W.II. 5. Long-term resident non-Charmorro and half-Chamorros on Guam are also affected. 6. Charmorro migrants to U.S. Mainland are affected after long absence from Guam. 7. Incubation period for both ways is estimated to be 18 approximately 20 years. 8. Other forms of dementias like Alzheimer disease (AD) and vascular dementias are on the rise and the leading cause of death is cerebro- and cardiovascular diseases. 9. ALS is also declining in past 10 approximately 15 years in Kii peninsula, and West New Guinea. Changing Ecology of Guam: 1. One third of Island land was used for construction of huge military bases after W.W.II. 2. Urbanization of villages including concrete houses, deep well water supply, sewage, and electrification. 3. Tourism boom: high-rise hotels, development of 7 golf courses and other recreational facilities resulted in loss of flora and erosions of soil. Socioeconomic Changes: 1. Shift in population demography; Efflux of Chamorros and influx of aliens; Chamorros less than 50% by 1990. 2. Tourists passed 1 million in 1994. 3. Automobiles 1 car/1.5 person. 4. Westernization: After W.W.II, almost free access to Military Commissary for imported food and appliances. 5. Life style: from food collection to wage-based society. Genetic Studies: 1. Familial aggregations, but no clear-cut Mendelian inheritance. 2. Segregation analysis: no absolute genetic or environmental cause but additive gene component may play a role in genetic susceptibility and basis for geographical clustering. 3. Absence of Apo-E or Mu/Zn SOD genes. 4. Recent discovery of mtDNA Complex I deficiency in Parkinsonism-dementia cases suggests mitochondrial DNA abnormality. Comparative Environmental Studies: 1. Environmental studies in three hyperendemic areas in the Western Pacific--Kii, Marianas, and west New Guinea, where strikingly high incidences of ALS is known to occur, found the identical geochemical environment--low Ca, Mg, and Zn and high A1, Mn, Fe, Si, in the garden soil and drinking water. 2. Exogenous etiologic factors that are absent from primitive culture of Auyu and Jackai tribes in West New Guinea were eliminated. 3. Cycad neurotoxicity has been excluded. 4. Suspected exogenous agents that are common in these 3 hyperendemic areas are (a) locally grown vegetables, starchy roots, and reef fish; (b) surface water containing soluble organic minerals from red laterites; (c) rain water that is chemically pure and lack of essential minerals. Pathogenic Speculation: Chronic dietary deficiency since birth in Ca, Mg and Zn induced excessive absorption of divalent cations which accelerates oxidant-mediated neuronal degenerations in a genetically susceptible population. The process is probably carried through interactions between cytoskeletal abnormality of the neuron, aging process, abnormal proteins, and mitochondrial dysfunction.

Diffuse Lewy body disease

Abstract: Diffuse Lewy body disease (DLBD), which we have proposed since 1976, has received great attention among both researchers and clinicians. Recently, it was reported by some English and American research groups that DLBD is the second most frequent dementing illness in the elderly, following Alzheimer-type dementia (ATD). Our recent research of 79 autopsied dementia cases in a hospital disclosed that DLBD (15.4%) was the second most common degenerative dementia, following ATD (43.6%). In 1980 we proposed Lewy body disease, and classified it into three types: brain stem type, transitional type, and diffuse type. Diffuse type of LBD is now called DLBD. In 1990 we divided DLBD into two forms: common form and pure form. The common form of DLBD has more or less Alzheimer pathology, and pure form has none. Very recently, we proposed the cerebral type of LBD, in which numerous Lewy bodies are found in the cerebral cortex and amygdala, but no PD pathology is present in the brain stem. Therefore, LBD is now classified as follows: [table: see text]

[Clinical difference between "proximal" and "distal" type of cervical spondylotic amyotrophy].

Abstract: We studied 31 patients with cervical spondylotic amyotrophy. Weakness and atrophy without prominent sensory changes were started from the proximal muscles in 16 patients (proximal type), and from the distal muscles in 15 patients (distal type). In both types, the age at onset of neurological symptom ranged from thirties to sixties, and men were more frequently affected than women. Distal type patients often presented cold paresis and/or postural finger tremor, which occasionally was the initial symptom. Two patients of proximal type had muscular atrophy extended to the distal end. None of distal type patients had extension of atrophy to the proximal muscles during a long course of their illness. Most patients of proximal type had neurogenic changes on electromyography extended to the distal muscles. Neuroradiologically, proximal type patients had a cord atrophy at C4/5 intervertebral level, and distal type had cord atrophy at C5/6,6/7. We assume that the responsible lesion for the cervical spondylotic amyotrophy is in anterior horn at C5-T1 cord level for the proximal type, and at C7-T1 for the distal type. Abnormal venous circulation within the cord may cause the selective involvement of the gray matter.

Intravascular malignant lymphomatosis

Abstract: Based on our personal experience of two cases of intravascular malignant lymphomatosis (IML) and a review of 128 cases in the literature, the possibilities for clinical diagnosis and successful treatment of this condition are discussed. IML usually presents with hemiparesis or progressive dementia and then with disturbances of consciousness. Paraparesis and dysuria due to spinal cord involvement are not rare. Since increased levels of blood sedimentation rate, CRP, serum LDH, and CSF protein are often observed in the patients, a diagnosis of IML must be included among the list of differential diagnoses when these findings are encountered in a patient presenting with clinical features similar to those of cerebrovascular diseases or multiinfarct dementia. The diagnosis must be confirmed histologically, so that an appropriate treatment can be initiated early in the course of the disease. Skin biopsy is indicated when skin eruption is present. Autopsy records of patients have revealed involvement of intravascular lymphoma to the kidney, adrenals, lungs and liver in more than 80% of cases. It is suggested therefore that biopsies are performed for these organs. Muscle biopsy can also be useful for making a diagnosis. Since autopsy studies have revealed swelling of the adrenals in some cases, including ours, CT or MRI images of the adrenals might be of importance. Regarding treatment, chemotherapy must be indicated. However, this has so far shown either no or only a temporary efficacy, partly because of the delay in reaching a diagnosis. A cure for IML could be expected through early initiation of combined treatment with various chemotherapeutic agents in the near future.

[Nocturnal hypoxia index: a new pulse oxymetry index of nocturnal hypoventilation in neuromuscular disorders].

Abstract: Respiratory insufficiency due to progressive muscle wasting is a major cause of death in various neuromuscular disorders. Morning headache and anorexia leading to slowly progressive body weight loss are frequently observed as initial symptoms of insufficient ventilation. From our experience nocturnal pulse oxymetry is a valuable study to detect early respiratory insufficiency and helpful to evaluate the effectiveness of ventilatory assistance, since ventilation is more impaired during sleep in early stage of respiratory insufficiency. Percent desaturation time (total desaturation time (SaO2 or = SaO2 > 90%) + (% time of 90% > or = SaO2 > 85%) x 2 + (% time of 85% > or = SaO2 > 80%) x 3 + (% time of 80% > or = SaO2 > 75%) x 4 + (% time of 75% > or = SaO2 > 70%) x 5.... This index is good for any stage of respiratory failure, and applicable to nocturnal hypoxia of other causes. The criteria for initiating mechanical ventilation in DMD can be substituted by "NHI is above 130."

Auditory disturbance induced by carbamazepine administration in a patient with secondary generalized seizure

Abstract: We report on an 18-year-old woman with secondary generalized seizure, who developed an auditory disturbance (flat a tone) after carbamazepine (CBZ) administration. She used to have brief episodes of conjugate deviation of the eyes to the right, head heaviness, teleopsia, and visual hallucination since 16 years of age. At the age of 18 years, she developed a tonic-clonic seizures during sleep, and was placed on CBZ 400 mg/day. Immediately after taking the medication, she developed auditory disturbance while she played the musical instruments: she felt as if she played the musical note almost a half tone lower. On admission, neurological examinations and magnetic resonance images of the brain were normal. Electroencephalogram at rest was normal. However, intravenous diphenhydramine injection induced spikes in the left temporo-occipital region, followed by diffuse spike and wave complex. Although the serum CBZ level was reduced to the therapeutic level by lowering CBZ administration from 200 to 150 mg/day, she continued to have the same auditory disturbance. When CBZ administration was discontinued, the symptoms also disappeared. It remains unknown whether such a subtle side effect of CBZ is a common thing, or it can be recognized only by persons who are well trained in music.

[A case of biopsy-proven sarcoid meningoencephalitis presented with hallucination, nominal aphasia and dementia].

Abstract: Here we report a 36-year-old male with sarcoid meningoencephalitis who initially presented with hallucination, nominal aphasia and disturbance of consciousness. After the onset, his symptoms fluctuated. He had no meningeal signs, and his cranial nerves were normal except for bilateral papapilledema. Muscle power and tone was normal, and there was no gait disturbance. Deep tendon reflexes were slightly exaggerated in lower extremities, but no pathological reflexes were noted. There was no impairment in extrapyramidal system, cerebellar system and sensory system. The cerebrospinal fluid revealed increased opening pressure, mild lymphocytic pleocytosis, slightly decreased glucose, increased protein to 87mg/dl and increased IgG index to 1.11. Cerebrospinal fluid culture was negative. Marked meningeal thickening and contrast enhancement was shown by CT and MRI. The meningeal biopsy demonstrated characteristic sarcoid nodules and confirmed the diagnosis of neurosarcoidosis. His manifestations were alleviated by oral administration of corticosteroid. Since neurosarcoidosis is a disorder treatable with corticosteroid, it is important to consider the possibility of this disorder in mind when a patient is presenting with psychiatric manifestations and chronic meningitis.

[A case of variant Gerstmann-Sträussler-Scheinker disease with the mutation of codon P105L]

Abstract: Here we present a case of variant GSS disease with mutations in codons 1055 and 129 in a prion protein. The patient was a 54-year-old male, who developed weakness in the lower limbs and spastic, wide-based gait at the age of 46 years. Subsequently he developed dementia and spastic quadriplegia at the age of 49. He had marked pseudobulbar palsy at the age of 50 and became bed-ridden in decorticated posture at teh age of 53. CT and MRI examinations revealed marked atrophy of the frontal and temporal lobes, but the occipital lobes and the cerebellum were spared. His sister had been reported by Amano, et al. in 1992 as a case of variant GSS syndrome, who had very similar clinical features, and had numerous prion protein positive plaques in her cerebral cortex at the time of autopsy. His sister was confirmed to have the same mutations in a prion protein as the present case in later genetic studies.

Functional MRI of the brain

Abstract: An introduction to functional MRI (fMRI) of the brain was described. Basically there are two methods in fMRI; one is using extrinsic substance and the other intrinsic substance. The blood oxygen level dependent contrast method, which uses intrinsic substance, is used commonly at present. This method is based on the idea that the signal intensity changes due to the oxygenation of hemoglobin (Hb) in the blood vessels. Oxy-Hb has a diamagnetic property which does not affect the signal intensity of water proton. On the other hand, deoxy-Hb is paramagnetic and shortens the T2 relaxation time of the water proton. By the activation of brain, blood flow increases around the activated area with a little increase of oxygen consumption, resulting in an increase of oxy-Hb in the capillary of this area. Consequently signal increase occurs in the activated area of the brain on MRI due to the decrease of deoxy-Hb. The fMRI was measured by pulse sequences sensitive to the T2 changes such as echo planar imaging (EPI) on 1.5 T systems or gradient echo imaging (GRE) on high-filed magnetic systems (3.0-4.0 T). It becomes possible to get fMRI on conventional MRI scanners using GRE pulse sequence. Many activation tasks are adopted for fMRI; not only simple tasks such as motor, photic and sensory stimulations but also complex tasks such as hearing of words, word generation, imagination, coordination motion, etc. A rapid increase of signal intensity was observed in the primary cortical area corresponding to each task, and the activated area is visualized by the subtraction imaging or statistically treated imaging. The fMRI has big advantages to get brain functional imaging because of non-invasive measurement, using intrinsic substance, highly spatial and temporal resolution and easy measurement on conventional clinical devices. Therefore, the fMRI will be used more and more widely in future, especially by introducing the EPI technique to the clinical MRI scanners.

[A case of HLA-DR2, DQw1 negative post-traumatic narcolepsy].

Abstract: We reported a case of a 24-year-old man who had frequent sleep attacks beginning 4 years after a head trauma. He showed frequent episodes of excessive daytime sleepiness and cataplexy which were triggered by emotional excitement. He also complained of sleep paralysis and hypnagogic hallucination. An overnight polysomnography revealed the sleep onset REM stage as typically observed in narcoleptic patients. The HLA typing was negative for DR2 and DQw1. He was diagnosed as having HLA-DR2 and DQw1 negative-post-traumatic narcolepsy. Peroral pemoline suppressed excessive daytime sleepiness, sleep paralysis and hypnagogic hallucination with dramatic relief of cataplectic attacks by the addition of imipramine. It has been reported that more than 90% of narcoleptic patients are HLA-DR2 and-DQw1 positive. About 10% of the narcolepsy patients were regarded as symptomatic due to brain tumors, cerebrovascular disorders, head trauma, multiple sclerosis, encephalitis and so on, which mainly affect the brainstem or diencephalon. Thus far, narcolepsy is considered to develop depending on both the genetic background including HLA types, and exogenous factors. According to reported cases with narcolepsy, sporadic cases were HLA-DR2 positive even more frequently than familial cases. To date, however, there have been only three previous reports of a symptomatic narcolepsy patient without association of HLA-DR2 and DQw1. In conclusion, the present report suggests that typical symptomatic narcolepsy could be HLA-DR2 or DQw1 negative.

[Rest-activity and body-temperature rhythm disorders in elderly patients with dementia--senile dementia of Alzheimer's type and multi-infarct dementia].

Abstract: We simultaneously monitored rest-activity and body temperature (BT) rhythm in demented patients with sleep and behavior disorders using ambulatory wrist-worn actigraph and long-term monitoring system for 5-7 consecutive days. Subjects consisted of 19 patients with senile dementia of Alzheimer's type (SDAT) (M/F = 7/12, mean age = 71.7 years), 16 patients with multi-infarct dementia (MID) (M/F = 9/7, mean age = 75.2 years) and 9 normal controls (M/F = 4/5, mean age = 70.4 years). Both dementia groups showed a significant increase in percentage of nighttime activity. In the SDAT group, a significant positive correlation between the degree of dementia and total activity was observed, but not observed in the MID group. A significant high amplitude of BT rhythm was observed in the SDAT group comparing that in the MID or the control group. These findings indicate that the SDAT patients had a disrupted rest-activity rhythm with the severity of intellectual deterioration and increased night activity, while the circadian BT rhythm was remarkably well preserved, i.e. there was a dissociation between rest-activity and BT rhythms in the SDAT group. On the other hand, the disruption of the rest-activity and BT rhythm in the MID patients was characterized by a concomitant decrease of amplitude, which seems to have no relation with the severity of dementia. Different mechanisms could be involved in characteristic disruption of the circadian rhythms in the 2 dementia groups.

[A case of multiple cranial neuropathy due to varicella-zoster virus infection: detection of involvement of cranial ganglia with MRI].

Abstract: We describe here a 50-year-old patient who had multiple cranial nerve palsies (lt.VIII,IX,X,XI and rt.VII, IX,X) with varicella-zoster virus (VZV). He developed hoarseness, dysphagia on 30th, November, 1994. On the 8th day after the onset, he suffered from left tinnitus and left facial nerve palsy. Neurological examination on the 10th day revealed left peripheral facial nerve palsy, lt. vocal cord palsy, mild dysphagia and loss of bilateral taste. He did not show signs of meningeal irritation. On the 11th day, he felt vertigo and had horizontal nystagmus on the right lateral gaze. The cerebrospinal fluid findings revealed increased protein content but not pleocytosis. The antibody titer for varicella zoster virus elevated both in cerebrospinal fluid and in serum. Cranial magnetic resonance imaging (MRI) revealed gadlinium enhancement on the left geniculate ganglion and left superior or inferior ganglion of IX and X nerves, indicating that multiple cranial nerve palsies associated with VZV infection originate in the cranial ganglia. Focal brainstem encephalitis does not seem to be the main cause of multiple cranial neuropathy in this case.

[Development of Wernicke's encephalopathy during the period of oral food intake after a subtotal colectomy for ulcerative colitis]

Abstract: A 61-year-old woman was hospitalized because of ulcerative colitis which had caused fever, vomiting and diarrhea since June 16, 1992. Then she developed toxic megacolon, and was transferred to our hospital on the 1st of July and underwent subtotal colectomy the same day. After surgery, she received intravenous hyperalimentation (IVH) which contained 1,000 Kcal/day without vitamin supplementation. From the 8th to the 13th post-operative days, she took 3/4 or more of the liquid diet which contained 1,050 Kcal, protein 35 g, carbohydrate 166 g and vitamin B1 0.59 mg per day. From the 14th to the 23rd post-operative days, she ate 4/5 or more of the oral diet which contained 1,700 Kcal/day, protein 68 g, carbohydrate 236 g and vitamin B1 0.93 mg per day. During the 7th to the 23rd day, the IVH was reduced to 800 Kcal and then 500 Kcal per day. She talked less on the 19th post-operative day, and in a few days, her level of consciousness began to decline progressively. On the 27th post-operative day, neurological examinations revealed the following: semi-coma, almost fixed pupils which were 3 mm in diameter, absent doll's eye movement to all directions, flaccid extremities with abolished deep tendon reflexes. Pertinent abnormalities on laboratory data at that time consisted of hemoglobin 7.8 g/dl and serum total protein 5.4 g/dl. Lumbar puncture revealed normal cerebrospinal fluid under normal opening pressure. Cranial magnetic resonance imaging (MRI) taken on the 27th post-operative day demonstrated, on T2-weighted images, symmetrical high intensity lesions in the periventricular areas of the third and fourth ventricles, and periaqueductal area of the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of optic neuropathy, recurrent transverse myelopathy and hypertrophic pachymeningitis associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)].

Abstract: A 77-year-old woman developed recurrent transverse myelopathy of the thoracic cord about a year after acute retrobulbar optic neuropathy on the left. Neurological examination revealed paraplegia, total sensory loss down from the level of the sixth thoracic cord and sphincteric disturbances. Her clinical features resembled multiple sclerosis, but magnetic resonance imaging (MRI) of the brain and spinal cord revealed no evidence of demyelination or inflammation. MRI of the brain showed the tentorium cerebelli on the right of low signal in T1- and T2-weighted images with marked enhancement by gadolinium, indicating pachymeningitis. Characteristically, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) together with antinuclear antibody was positive, whereas lupus anticoagulant and anti-cardiolipin antibody were negative. A high dose of corticosteroid including pulse therapy did not improve her symptoms. In the present case, the optic neuropathy, recurrent transverse myelopathy and hypertrophic pachymeningitis may have been caused by some common inflammatory processes related with p-ANCA.

Siblings of early onset cerebellar ataxia with hypoalbuminemia

Abstract: Recently, a new syndrome of early onset cerebellar ataxia with hypoalbuminemia (EOCA-HA) was reported in Japan. The clinical features of EOCA-HA overlap with those of Friedreich's ataxia (FA), and primary hypoalbuminemia is a characteristic laboratory finding of this syndrome. Genetic linkage analysis of EOCA-HA including this newly reported family revealed that the gene for EOCA-HA is located on the long arm of chromosome 9 as FA. However, several recombination events were observed between D9S15 in EOCA-HA, whereas no recombination events were seen in FA. We report on two siblings with EOCA-HA and discuss the clinical and laboratory features. The patients were a 25-year-old man (patient 1) and a 23-year-old man (patient 2). Their parents marriage was non-consanguineous. The mode of inheritance is compatible with autosomal recessive mode. Clinically, they showed cerebellar ataxia as the initial symptom in the late infantile period and subsequently showed choreoathetosis and ocular motor apraxia at the age of approximately fifteen years. Deep tendon reflexes were reduced in late infancy and finally disappeared. Amyotrophy and sensory impairment of the legs developed at approximately twenty. Abnormal electrocardiogram and diabetes mellitus were not observed. On X-ray CT scan or MRI, the cerebella of both patients were mildly atrophic. Clinical features in these siblings were indistinguishable from those of ataxia telangiectasia, but immunodeficiency syndrome was absent.(ABSTRACT TRUNCATED AT 250 WORDS)

[An autopsied case of dominantly affecting upper motor neuron with atrophy of the frontal and temporal lobes--with special reference to primary lateral sclerosis]

Abstract: In this paper, the autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. His clinical symptoms were slowly progressive spasticity, pseudobulbar palsy and character change. He died of sepsis 32 months after protracting the disease. The autopsy revealed severe atrophy of the frontal and temporal lobes. The histological findings were severe neuronal loss with gliosis in the precentral gyrus and left temporal lobe tip, loss of Betz cell, prominent demyelination throughout of the corticospinal tract, axonal swelling in the cerebral peduncule, severe degeneration of the amygdala, mild degeneration of the Ammon horn, normal substantia nigra, a few neuronal cells with central chromatolysis in the facial nerve nucleus and very mild neuronal cell loss in the spinal anterior horn. The anterior horn cell only occasionally demonstrated Bunina body by H & E and cystatin-C stainings, as well as, skein-like inclusion by ubiquitin staining. Thus, this is a case of uncommon amyotrophic lateral sclerosis (ALS) dominantly affecting the upper motor neuron including the motor cortex and temporal limbic system. In analysis of nine cases of putative primary lateral sclerosis in the literature, six cases showed loss of Betz cell in the precentral gyrus, and four cases very mild involvement of the lower motor neuron such as central chromatolysis and eosinophilic inclusion body. Degeneration of the limbic system was observed in two cases. We indicated a possible subgroup with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease dominantly affecting the upper motor neuron.

[Treatment of spastic paraparesis with botulinum toxin with reference to beneficial effects, disease severity and long-term treatment].

Abstract: We administered local botulinum toxin injections on the leg adductors of 12 patients with spastic paraparesis (9 patients with HAM, 2 patients with spinal spastic paraparesis, 1 patient with an identified degenerative disease). Two of them were wheelchair-bound and the other patients could walk with or without help. The patients were assessed by the time to walk 10 m and the spasticity score which was derived from the degree of muscle tone and spasm frequency of leg adductors. After the initial injection, 7 of the 12 patients improved spasticity scores and 8 of the 10 patients could walk 10 m within a shorter time. The time to walk 10 m was markedly shortened in moderate cases. However, one patient complained of leg weakness and the time to walk 10 m was prolonged. Five of the 12 patients received injections 3 to 7 times, and were followed up for a mean of 16.2 months. In 4 of the 5 patients, repeated injections could maintain the improvement of spasticity score and time to walk 10 m. However, injection was discontinued in one patient because of leg weakness. The other side effects were pain and swelling at the injected site and dysarthria. However, these side effects were slight and transient and did not require treatment. No other systemic side effects were observed. In conclusion, the beneficial effects of botulinum injections to spastic paraparesis were (1) improvement of objective symptoms in mild cases, (2) improvement of ADL in moderate cases, and (3) improvement of objective symptoms and ease of nursing care in severe cases. Furthermore, we confirmed the long-term efficacy and safety of botulinum toxin.

Clinicopathological report of cisplatin encephalopathy

Abstract: A 61-year-old woman was treated with cisplatin and etoposide for ovarian carcinoma. After the second course of chemotherapy she developed acute encephalopathy which manifested itself as headache, fever, a partial seizure, confusion, and mild right hemiparesis, although no evidence of a central nervous system infection was found. Ten days after the onset of neurological symptoms, she experienced a sudden loss of vision in both eyes. Neurological findings were compatible with cortical blindness. Neurological symptoms subsided and visual acuity completely returned over the next months. The total cumulative dose of cisplatin was 325 mg/m2. She died of aspiration pneumonia on the 43rd day. Postmortem examination revealed severe nerve cell loss, gliosis and spongy changes in the bilateral occipital cortex including visual field, and slight to moderate demyelination in the subcortical white matter of the occipital cortex, Goll's tract, and dorsal root ganglia. As far as we know this encephalopathy is the second report in which the neuropathological changes associated with cisplatin therapy have been demonstrated by autopsy findings. The first was a case report of leukoencephalopathy, which differed significantly from our case in the primary lesions of the brain. We measured the platinum level in several parts of the cerebrum and cerebellum, optic nerve, spinal cord, and cauda equina by using an atomic absorption spectrophotometric technique. Platinum was detected in the bilateral occipital cortex, spinal cord, and cauda equina. These results were consistent with the distribution of pathological lesions. The mechanism of cisplatin-induced focal encephalopathy remains speculative.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of severe sarin poisoning in the sarin attack in Matsumoto--one-year follow-up of clinical findings, and laboratory data].

Abstract: A patient severely poisoned with sarin in the Sarin Attack in Matsumoto is described. A 19-year-old man was exposed to sarin at 23:00 on 27 June, 1994. At 1:00 of the following day, a rescue team found and brought him to the hospital. His blood pressure was 150-80mmHg and the heart rate was 120/min with frequent premature ventricular contractions (PVC). His respiration was shallow and copious salivation and excretion from the respiratory tract were observed. Consciousness disturbance, generalized convulsion, severe miosis and fasciculation of tongue, facial muscle and extremities were also marked. Serum cholinesterase was 21 U/l (normal 109-249) and acetylcholinesterase in erythrocyte (E-AchE) was 0.1U/l (normal 1.2-2.0). Electroencephalogram (EEG) 30 hours after exposure showed polispike and wave complexes. Ventilatory assistance, forced urination and injection of diazepam and atropin improved his general condition and he was discharged 18 days after exposure. Three months after exposure, E-AchE was normalized and there was no complaint. But one year after exposure, EEG showed epilecpic discharges during sleep, and Holter electrocardiogram showed frequent PVC. As no clinical cases of severe sarin poisoning like this patient was reported, a longterm follow-up of this patient is very important.

Correlative study of the brain CT and clinical features of patients with Down's syndrome in three clinical stages of Alzheimer type dementia

Abstract: Patients with Down's syndrome often develop Alzheimer type neuropathological changes as well as dementia of the Alzheimer type after the age of 40. We studied brain CT findings in relation to three clinical stages of Alzheimer type dementia in 11 patients with Down's syndrome aged from 17 to 55 years. In addition, 123I-IMP-SPECT was studied in 4 of these patients. Dementia of the Alzheimer type was present in 9 patients; 5 patients were in the early stage, 2 were in the progressive stage, and the other 2 were in the end stage. The earliest CT finding was enlargement of the suprasellar cistern, which indicated atrophy of the medial temporal lobe including the hippocampus and amygdala. This finding was not present in non-demented individuals with Down's syndrome. Moreover, CT scans showed that brain atrophy progressed to the temporal, frontal lobe, and then generalized cerebral cortices, which correlated clinically with the severity of dementia. Studies of 123I-IMP-SPECT in two patients with mild dementia revealed abnormally decreased isotope uptake in the temporal and posterior parietal regions. We suggest to measure the size of the suprasellar cistern in CT and SPECT scans for early detection and diagnosis of mild dementia of the Alzheimer type in patients with Down's syndrome.

[Marked clinical improvement by plasmapheresis in a patient with stiff-man syndrome: a case with a negative anti-GAD antibody].

Abstract: We described a 56-year-old man with stiff-man syndrome, who was markedly improved after plasmapheresis therapy. He had a 12-year history of progressive painful stiffness of his back and limbs, muscle cramps and difficulty in walking. He had been taking oral diazepam and prednisolone. On examination the abdominal and paraspinal muscles and limbs were continuously contracting, confirmed by surface and needle electromyography. Antibodies against glutamic acid decarboxylase (GAD) and pancreatic islet cells in the serum were negative, but antinuclear antibody and anti-smooth-muscle antibody were present. The patient underwent a course of 4 double filtration plasma exchanges of 3,000 ml each in an 8-day period. Plasmapheresis resulted in marked clinical improvement. The disappearance of muscular cramps and a reduction of stiffness occurred within 24 hours after the first plasmapheresis, and he was able to walk unassisted. The patient's subjective improvement continued over 4 months after the plasma exchange. This case provides additional evidence of the autoimmune mechanism of stiff-man syndrome. Plasmapheresis is one choice in the management for stiff-man syndrome.

[A clinicopathological study of the Guillain-Barré syndrome--fifteen Japanese postmortem cases].

Abstract: The postmortem findings of the ventral roots and ventral horn cells of 15 Japanese cases of Guillain-Barre syndrome are reported. In 5 cases there was predominant axonal involvement with severe axon loss in the lumber ventral root. Eight cases showed predominantly segmental demyelination, and two cases were the intermediate form with both segmental and axonal changes. Macrophage invasion in the ventral roots predominantly occurred in the cases with axonal involvement. Large-sized motor neuron loss and reactive astrogliosis were also seen in the cases with axonal degeneration. These findings indicate that approximately 30% of Japanese autopsied cases were "axonal form", the incidence of which was higher than that reported in European and North American countries, but was lower than that in Chinese endemic acute motor axonal neuropathy.

[An autopsy-verified case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180 point mutation].

Abstract: An autopsied case of Creutzfeldt-Jakob disease is reported. A 79-year-old Japanese female showed extrapyramidal sign (resting tremor, and rigidity) and dementia. She developed myoclonus and became akinetic within one year from the onset, and then died of pneumonia at age of 81. None of the members of her family had neuromuscular disorders. CT and MRI studies revealed progressive brain atrophy. Consecutive study of EEG did not reveal periodic synchronous discharges (PSD). Codon 129 polymorphism (Met/Val) and codon 180 point mutation (Val/Ile) were detected. The autopsy revealed spongiform change of cerebral cortex and negative Kuru plaques, confirming the diagnosis of Creutzfeldt-Jakob disease. Immunohistochemical study revealed weak synaptic prion staining. Western blot analysis showed positive Proteinase K resistant prion protein. Gene analysis of autopsied brain showed the same prion DNA polymorphism and mutation. The combination of codon 129 polymorphism and 180 point mutation might associate with an atypical clinical form of CJD, which shows the extrapyramidal signs at the onset, and negative PSD in EEG.

Meningeal seeding of spinal cord glioblastoma multiforme without any signs of myelopathy

Abstract: An autopsy case of meningeal spreading of glioblastoma multiforme (GBM) probably originating in the cervical cord was reported. In contrast to autopsy findings, main symptoms were similar to subacute meningitis, and any signs of myelopathy could not be detected during the clinical course. The patient was a 22-year-old man who was hospitalized because of a 2-week history of progressive headache following cough and slight fever. Vomiting and somnolence, developing 5 days before admission, were improved the day after a lumbar puncture performed at another hospital. On admission, meningeal signs, mild right abducens palsy, and depressed deep tendon reflexes were detected. There was no muscle weakness, sensory loss, or Babinski sign. Lumbar puncture yielded CSF with an opening pressure of 280 mmH2O, 21 mononuclear cells/mm3, a protein level of 645 mg/dl, and a glucose level of 7 mg/dl. Cytology for malignancy and multiple cultures were negative. Brain CT scan showed mild hydrocephalus and swelling of the brainstem and cerebellum. Intravenous administration of antimicrobial drugs was started and ventriculoperitoneal shunt surgery was performed. During the third hospital week, however, meningeal signs progressed and somnolence reappeared, followed by progressive multiple cranial neuropathy and polyradiculopathy characterized by flaccid tetraparesis, muscle atrophy, and sensory impairment without a level. Babinski sign could not be detected. MRI revealed an intramedullary lesion in the lower cervical cord, swelling of the brainstem, cerebellum, spinal cord and nerve roots, and a diffuse or nodular thickning of leptomeninges. Repeated CSF cytology disclosed atypical cells. Examinations for extraneural malignancies were negative. During the 9th hospital week, flaccid tetraplegia progressed and stupor developed, and the patient died 2 weeks later. The pathological study was limited to the brain. The brain showed a diffuse opalescent thickening of the leptomeninges, especially over the ventral aspect of the brainstem and cerebellum, where the blood vesseles and cranial nerves were obscured. Histological examination revealed the appearance of GBM. The malignant cells filled the subarachnoid space, and to a variable extent penetrated the brainstem and cerebellum along perivascular spaces. Hypertrophied optic tracts and trigeminal nerves were also infiltrated by the cells. However, there were no mass lesions assumed to be primary ones anywhere in the cerebral parenchyma. Therefore, it was thought that GBM primarily growing in cervical cord metastasized to intracranial subarachnoid space by way of the cerebrospinal fluid pathway. Spinal cord GBM usually presents signs of myelopathy from the early stage. The present case was characterized by no signs of myelopathy during the clinical course. It is speculated that the intramedullary GBM, originating near the surface of cervical cord, had been rapidly disseminated into the subarachnoid space up to the intracranial cavity before myelopathy appeared, and caused cranial and spinal nerve roots dysfunction, which covered signs of myelopathy. Cord GBM should be always considered as a differential diagnesis in a case of subacute meningitis.

Deficiency of human ciliary neurotropic factor (CNTF) is not causally related to amyotrophic lateral sclerosis (ALS)

Abstract: Ciliary neurotrophic factor (CNTF) promotes the survival of motor neurons in vitro and in vivo. A recent report showed that disruption of the CNTF gene in mice caused motor neuron degeneration. We have found a null mutation in the human CNTF gene. The mutated allele shows a G to A transition producing a new splice acceptor site and the resulting mRNA species codes for an aberrant protein. Analysis of tissue samples demonstrated that the mutated allele expressed only the mutated mRNA species. In 391 Japanese people tested, 61.9% were normal homozygotes, 35.8% heterozygotes and 2.3% mutant homozygotes. The distribution of the three genotypes is similar in healthy and neurological disease subjects including ALS patients. Our findings indicate that CNTF deficiency is not causally related to ALS.

A case of metamorphopsia caused by a very localized spotty infarct

Abstract: A 51-year-old woman complained that her right side of the face looked blurring and the right margin of all the objects in her visual field looked blurred. Neurological examination on admission showed no abnormalities including higher cortical function and visual fields except the metamorphopsia. In this case, a very localized spotty infarct caused no neurological symptoms other than the metamorphopsia. CT scan and MRI revealed a spotty lesion of infarct between retrosplenium and cingulate gyrus on the left side. This can be a breakthrough case to locate the exact anatomic pathology that causes metamorphopsia.

Neuropathology of syringomyelia

Abstract: Eighteen autopsy cases of syringomyelia were studied neuropathologically. In 5 cases associated with Chiari type I malformation, the syrinx was irregular in shape and communicated with the subarachnoid space at the entry zone of the posterior nerve roots. The central canal above the level of the syrinx was patent in 2 but closed in 3 out of 5 cases. In cases associated with Chiari type I malformation, communication between the syrinx and the subarachnoid space was considered to play an important role in the pathogenesis of syringomyelia. In 6 cases associated with Chiari type II malformation, the syrinx central canal, and the central canal was patent from the 4th ventricle to the syrinx in all cases. In these cases, direct continuity between the 4th ventricle and the syrinx was essential for the development of the syrinx. In cases associated with posterior fossa or spinal canal tumors, the local circulatory disturbance and/or edema due to the tumors were thought to cause the syrinx.