Konagaya M

Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy.

Slit-hyperintensity in the outer margin of the putamen on T2 weighted MRI was found in 17 out of 28 patients with clinically diagnosed multiple system atrophy. Thirteen of these 17 patients showed extrapyramidal signs. Five patients had only unilateral slit-hyperintensity; four of them had contralateral rigidity; and one had bradykinesia. Despite mild rigidity, one case showed no slit-hyperintensity. One of the 14 cases with parkinsonism showed no hyperintensity, and four of the 14 cases without parkinsonism showed hyperintensity. On the other hand, slit-hyperintensity was not seen in any of 25 patients with clinically diagnosed Parkinsons disease. Putaminal slit-hyperintensity is a useful MRI feature in the differential diagnosis between Parkinsons disease and multiple system atrophy predominantly affecting the extrapyramidal system.

Clinical analysis of longstanding subacute myelo-optico-neuropathy: sequelae of clioquinol at 32 years after its ban

One thousand and thirty-one longstanding patients with subacute myelo-optico-neuropathy (SMON; 275 males, 756 females; mean age +/- S.D., 72.9 +/- 9.6 years; age at onset 37.6 +/- 9.8 years; duration of illness 35.3 +/- 4.0 years) were examined in 2002, 32 years after banning of clioquinol. At onset, 66.7% of patients were unable to walk, and 4.7% complete blindness. At present time, about 41% of patients were still difficult to walk independently, including 15.8% of completely loss of locomotion. One point six percent of patients were in complete blindness and 5.8% had severe visual impairment. The majority (95.6 - 97.7%) of patients exhibited sensory disturbances including superficial and vibratory sensations and dysesthesia. Dysautonomia was observed as leg hypothermia in 79.8%, urinary incontinence in 60.7%, and bowel disturbance in 95.3%. As complication, high incidence was revealed with cataract (56.2%), hypertension (40.2%), vertebral disease (35.5%), and limb articular disease (31.5%). These results indicate the serious sequelae of clioquinol intoxication, SMON.

Progressive cerebral atrophy in multiple system atrophy.

Nine patients with multiple system atrophy (MSA) were studied based on MRI findings of cerebral hemispheric involvement. The age at onset was 56.4+/-8.6 (mean+/-S.D.) years, duration of illness at the first MRI study 2.1+/-1.1 years, duration of illness at the last study 9.7+/-2.6 years, and the follow-up duration 7.6+/-2.3 years. Controls were 85 neurologically intact persons (60.2+/-11.1 years age). In the MRI study, measurements of the ratio of each area to the intracranial area were performed for the cerebral hemisphere, frontal, temporal and parietal-occipital lobes. A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes. Besides the typical pathological lesions in MSA, five autopsied patients revealed frontal lobe atrophy with mild gliosis, mild demyelination and glial cytoplasmic inclusions (GCIs). One of these patients showed remarkable frontal lobe atrophy with degenerative changes in the cerebral cortex. We observed the involvement of the cerebral hemisphere, especially the frontal lobe.

An autopsy case of spinal muscular atrophy type III (Kugelberg‐Welander disease)

We report an autopsy case of a 67‐year‐old man clinicogenetically diagnosed as having spinal muscular atrophy (SMA) type III (Kugelberg‐Welander disease), showing slowly progressive muscle wasting and weakness of the extremities. His brother showed similar manifestations. Autopsy revealed neuronal loss and severe gliosis in the anterior horns of the spinal cord, a marked neurogenic change of skeletal muscles and mild degeneration of cardiomyocytes. Chromatolytic change was seen in the anterior horn, but not in the Clarkes and thalamic nuclei. The anterior spinal roots were atrophic, and there was loss of myelinated fibers with abundant glial bundles. In addition, degeneration was also observed in the posterior column and dentate nucleus. The pathological features were essentially similar to those of SMA I. Chronic change was prominent while acute change was mild in degree, corresponding to a very long clinical course.

Autopsy case of hereditary spastic paraplegia with thin corpus callosum showing severe gliosis in the cerebral white matter

We report an autopsy case of a 51‐year‐old man clinically diagnosed with a complicated type of hereditary spastic paraplegia. His sister showed similar manifestations. Gait disturbance was manifested at 14 years of age. Subsequently, slowly progressive spastic tetraplegia developed with mental deterioration, neuropathy and amyotrophy. Marked cerebral atrophy with thin corpus callosum was shown by cranial MRI. Autopsy revealed a severely atrophic brain with extreme thinning of the whole corpus callosum. Microscopically, neurodegeneration was found in the corticospinal tract, thalamus, cerebral white matter and substantia nigra, as well as in the anterior horn and posterior column of the spinal cord. The remaining neurons contained large amounts of lipofuscin and eosinophilic granules. Unique to this patient was the severe gliosis in the cerebral white matter and substantia nigra, suggesting that sufficient development had been established when the degenerative process occurred. The predominant feature of the present case is the neurodegeneration process rather than hypoplasia.

Efficacy and tolerance of gastrostomy feeding in Japanese muscular dystrophy patients.

Although muscular dystrophy patients often have feeding difficulty and need long-term enteral nutrition, only a few reports have described gastrostomy feeding in these patients. This study was designed to evaluate the efficacy and tolerance of gastrostomy feeding in patients with muscular dystrophy. We performed a retrospective, multicenter study on 144 patients with muscular dystrophy who received gastrostomy feeding between 2007 and 2009 in 25 neuromuscular centers in Japan. There were 77 Duchenne muscular dystrophy (median age at gastrostomy placement 26 years, range 13-47 years), 40 myotonic dystrophy (median age 54.5 years, range 13-70 years), 11 Fukuyama congenital muscular dystrophy (median age 22 years, range 13-29 years), 5 limb girdle muscular dystrophy (median age 62 years, range 43-78 years), and 5 facioscapulohumeral muscular dystrophy (median age 52 years, range 28-67 years) patients. Many benefits including amelioration of malnutrition, swallowing difficulty and respiratory status were observed after the introduction of gastrostomy feeding. Especially in patients with Duchenne muscular dystrophy, mean body weight significantly increased after gastrostomy placement. Although most complications, which are commonly observed in other populations, were tolerable, respiratory failure and peritonitis were important concerns. These findings suggest that gastrostomy placement at an appropriate time is advisable in patients with muscular dystrophy.

Pathological correlate of the slitlike changes on MRI at the putaminal margin in multiple system atrophy.

Sirs: The slitlike signal changes at the lateral margin of the putamen on magnetic resonance imaging (MRI) is a characteristic finding in patients with multiple system atrophy (MSA) involving the extrapyramidal system [1–3]. The degree of signal change is correlated with the severity of extrapyramidal symptoms. However, in spite of some speculation whether to sign is due to demyelination, gliosis, iron deposition [2, 4], or increased extracellular fluid [1], the nature of the abnormal signal intensity has remained uncertain. We report the pathology and magnetic resonance imaging of the putaminal margin in a case of MSA. The patient was a 63-year-old woman with a 9-year history of parkinsonism. Neurological findings at age 59years were mild dementia, masked face, moderate bradykinesia with rigidity, small steppage gait with mild ataxia, mild incoordination, orthostatic hypotension, and dysuria. Study by 0.5-T MRI demonstrated a normal pontocerebellar system and slit-hyperintensity in outer marigin of the left putamen in the T2-weighted image. Antiparkinsonism drugs failed to improve her movement disorder. By the age of 60 she had become bedridden, and died of cardiac arrest at age 63. Six months prior to her death, 0.5-T MRI showed pontocerebellar system atrophy, slit-hyperintensity in both outer putaminal margins and the inner margin of the left putamen in T2weighted image (Fig.1), and linear hypointensity in the T1-weighted image (Fig.2). Hypointensity on T2weighted MRI was observed in the globus pallidus and putamen. The brain, removed at autopsy, was mildly atrophic in the frontal lobe and severely atrophic in the pons and cerebellum and weighted 1240g. The coronal section disclosed severe bilateral, symmetrical atrophy of the putamen which was brown in color (Fig.3). The caudate nuclei and globus pallidus were fairly well spared. The rarefaction or tissue space was observed at the outer putaminal margin in both sides and at the inner margin in the left side. Microscopic examination revealed diffuse rarefaction of the putamen associated with almost total loss of neurons and concomitant proliferation of astroglia. Iron deposition was present in the extracellar space and in the remaining cells of the putamen, especially in the dorsolateral portion. The neurons in the caudate nuclei, globus pallidus, and thalamus were well preserved. In the substantia nigra, there was moderate pigmented neuronal loss accompanied by astrocytosis. Loss of pigmented neurons was also observed in the locus caeruleus. Marked neuronal loss with gliosis was also observed in the pontine nuclei and inferior olive. In the cerebellum, Purkunje cell loss was marked in the vermis and moderate in the hemispheres, and the white matter was extremely atrophic with considerable gliosis. Glial cytoplasmic inclusions were observed in a widespread region of the brain. The patient had shown signs and symptoms of MSA, and the diagnosis was confirmed by postmortem studies. MRI during life revealed an abnormality that closely matched those of gross pathological findings in the putamina. The putaminal atrophy resulted in the formation of the intertissue space between the putamen and external capsule as well as LETTER TO THE EDITORS J Neurol (1999) 246 :142–143

The fluctuation of serum myoglobin levels in Duchenne muscular dystrophy and the carrier

The diurnal changes of serum myoglobin level and CK activity were investigated in 20 cases of Duchenne dystrophy and 6 normal males under ordinary circumstances in their daily lives. Changes of myoglobin levels were also checked in 25 cases of Duchenne carrier and 11 control females with muscular exercise by ergometer of 70 W for 3 min. In Duchenne dystrophy, the myoglobin level was rather low before waking up, then it abruptly increased thereafter and remained high until retiring. The fluctuation range of myoglobin was greater than that of CK. The myoglobin level of control males was extremely low compared with that in Duchenne dystrophy. In Duchenne carriers, although CK activity did not significantly change after the exercise, 5 of 11 known carriers showed an increased myoglobin level.

A clinical and pathological study of a Japanese case of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex with family history.

Abstract. This report concerns a Japanese family with neuropathological findings consistent with amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Island of Guam. The proband was a 68-year-old woman with an 8-year history of parkinsonism which was followed by psychiatric symptoms and neurogenic amyotrophy 5 years after the onset. She had a family history of parkinsonism associated with dementia in all of her three siblings. They grew up in the Hobara village, a focus of amyotrophic lateral sclerosis in the Kii Peninsula of Japan in their childhood. Their parents were not consanguineous nor natives of the Kii Peninsula. The brain weight was 1040 g and there were mild frontal lobe atrophy, moderate atrophy of pes hippocampi, decoloration of the substantia nigra and locus coeruleus, and atrophy of the anterior root of the spinal cord. The microscopic examinations revealed degeneration of CA1 portion of the hippocampus to the parahippocampus gyrus, substantia nigra, locus coeruleus and spinal anterior horn with Bunina bodies. The spinal pyramidal tracts also mildly degenerated. Neurofibrillary tangles (NFT) were observed in the cerebral cortex, especially in the cortices from hippocampus to lateral occipitotemporal gyri, basal nucleus of Mynert, basal ganglia, thalamus, substantia nigra and widespread regions of the central nervous system through the brainstem to spinal cord including the nucleus of Onufrowitcz. In spite of a small amount of the senile plaques in the cerebral cortex and Lewy bodies in the substantia nigra and locus coeruleus, abundant NFT were distributed mainly in the third layer of the cerebral cortex, which is the characteristic feature of ALS/PDC. Thus, this was likely to be an ALS/PDC case outside the Guam Island. A tau mutation was not found on DNA analysis.

Activities of daily living, functional capacity, and life satisfaction of subacute myelo-optico-neuropathy patients in Japan.

Background Patients with subacute myelo-optico-neuropathy (SMON) suffer from a number of serious neurological symptoms that adversely affect their activities of daily living (ADL). However, the effects of these neurological symptoms on functional capacity and life satisfaction have not been reported. Methods We analyzed data from 1,300 SMON patients aged 55–94 years that was obtained at medical check-ups carried out by the SMON Research Committee in 2004–2006 in Japan. The neurological symptoms investigated were visual impairment, dysbasia, symptoms of the lower extremities, and sensory symptoms. Neurological symptoms were classified by severity. The Barthel Index, the Tokyo Metropolitan Institute of Gerontology Index of Competence, and the participant’s response to the question “Are you satisfied with life?” were used to evaluate ADL, functional capacity, and life satisfaction, respectively. Data were analyzed using a proportional odds model with the scores for these items as ordinal dependent variables. Results For most neurological symptoms, scores for ADL, functional capacity, and life satisfaction were significantly lower in participants with severe or moderate neurological symptoms than in those with nearly normal results upon examination. The odds ratio for life satisfaction due to superior functional capacity was significant after adjustment for sex, age, and ADL score. Conclusion The presence of neurological symptoms in SMON patients was associated with low functional capacity, life satisfaction, and ADL. Our results suggest that the life satisfaction of SMON patients can be increased by improving their functional capacity.