Immunological abnormalities in patients with early-onset ataxia with ocular motor apraxia and hypoalbuminemia.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor ß-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.

The prevalence of dementia in subacute myelo-optico-neuropathy (SMON) patients who underwent medical checkups.

AIM: Subacute myelo-optico-neuropathy (SMON) is a known adverse effect of clioquinol use; however, clioquinol dissolves beta-amyloid aggregation in Alzheimer's disease (AD). Therefore, we investigated the prevalence of dementia in SMON patients and whether past clioquinol use affected the current incidence of AD. METHODS: We included 647 SMON patients (195 men, 452 women; mean age 77.9 years) who had undergone medical checkups including the mini-mental state examination (MMSE) in 2012. Of them, 105 patients scored ≤23 on the MMSE assessment. The presence/absence of dementia and disease backgrounds were obtained by a questionnaire. Then, using the medical checkup database, the correlation between the degree of severity when signs of SMON were at their worst and the concurrent presence or absence of AD at present was analyzed. RESULTS: In patients ≥65 years of age, the estimated prevalence of dementia was approximately 10.9% (95% confidence interval: 7.9%-13.8%). The concurrent presence of AD at present was not correlated with the past degree of SMON severity when the SMON signs were at their worst. CONCLUSIONS: The 10.9% prevalence of dementia in SMON patients was lower than a previously reported 15% prevalence found in the general population. According to these results, we cannot draw a definitive conclusion regarding the preventive effect of clioquinol on AD. Additionally, the lack of association between the onset of AD and past severity of SMON precludes definitive conclusions on the relationship between concurrent presence of AD and past clioquinol use.

Neck weakness is a potent prognostic factor in sporadic amyotrophic lateral sclerosis patients.

OBJECTIVE: To clarify the emergence of muscle weakness in regions of the body that affect survival, and deterioration in activities of daily living (ADL) in amyotrophic lateral sclerosis (ALS) patients. METHODS: We conducted a multicentre-based prospective cohort study of patients with ALS. We enrolled 401 sporadic patients with ALS. Death or the introduction of invasive ventilation was defined as the primary endpoint, and the time to five clinical markers of ADL deterioration associated with bulbar paralysis or limb weakness were defined as ADL milestones. Muscle weakness was assessed in the neck flexor muscles; the bilateral abductors of the shoulders; the bilateral wrist extensor muscles; the bilateral flexor muscles of the hips; and the bilateral ankle dorsiflexion muscles. We performed Cox proportional hazards regression analyses for the primary endpoint and the five ADL milestones, adjusting for known covariate prognostic factors for ALS. RESULTS: The Medical Research Council (MRC) score for the neck flexors was the most significant prognostic factor for the primary endpoint (HR 0.74, p<0.001), loss of speech (HR 0.66, p<0.001), and loss of swallowing function (HR 0.73, p<0.001), and was one of the significant prognostic factors for loss of upper limb function, difficulty turning in bed, and loss of walking ability (p=0.001, 0.002, and 0.008, respectively). The MRC score for the neck flexors was also a significant prognostic factor for covariates of the previously reported prognostic factors. CONCLUSIONS: Neck weakness is an independent prognostic factor for survival and deterioration in ADL in Patients with ALS.

[Cognitive function screening of community-dwelling elderly people using the clock drawing test -quantitative and qualitative analyses].

AIM: The purpose of this study was to evaluate whether the clock drawing test (CDT) is useful to assess the cognitive function of community-dwelling elderly people. We evaluated the CDT as a tool to measure cognitive function by qualitative and quantitative analyses. METHODS: A total of 14,949 community-dwelling elderly were invited by mail to undergo cognitive screening by CDT. Of these, 8,815 responded, of which 8,684 were eligible for enrollment. We were also able to determine the educational background of 7,404 of these. There were 3,525 men (age: 73.05±6.20 [mean±standard deviation] years old, duration of education: 11.40±2.81 years) and 3,879 women (73.67±6.66, 10.34±2.19) . The drawn clocks were evaluated using the Freedman method, and those clocks drawn with obvious errors such as no circle, numbers, or hands were recorded and analyzed. In addition, any vertical deviation from the center points was also evaluated. RESULTS: The recorded percentages of the subjects who correctly completed the individual clock drawing test components varied. The mean total scores were 14.16±1.67 in men and 14.40±1.36 in women. The percentages of subjects with total scores of less than 13 were 16.09% in men and 11.7% in women. The percentage of subjects who made obvious errors was 3.24%, whose total points were significantly lower than those of the subjects who did not. Approximately half of all subjects showed vertical deviation from the center of the clock, and the percentage of upper deviation was greater than that of lower deviation. CONCLUSION: CDT is useful to assess the cognitive function of community-dwelling elderly people, and it is also helpful to determine subjects with a potential risk of cognitive impairments.

Multiple system atrophy variant with severe hippocampal pathology.

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann-Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann-Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.

Change in activities of daily living, functional capacity, and life satisfaction in Japanese patients with subacute myelo-optico-neuropathy.

BACKGROUND: There have been few reports on longitudinal change in activities of daily living (ADL), functional capacity, and life satisfaction in patients with subacute myelo-optico-neuropathy (SMON). METHODS: A total of 1309 SMON patients 40 to 79 years of age underwent a medical examination conducted by the SMON Research Committee during the period from 1993 through 1995 (baseline) in Japan; 666 (51%) were followed-up after 12 years and were thus eligible for analysis. We calculated scores for ADL, functional capacity, and life satisfaction at baseline, and at 3, 6, 9, and 12 years after baseline, using data from medical examinations conducted in 1993 through 2007. The Barthel Index, the Tokyo Metropolitan Institute of Gerontology Index of Competence, and the patient's response to the question "Are you satisfied with life?" were used to assess ADL, functional capacity, and life satisfaction, respectively. RESULTS: As compared with baseline, the mean scores for ADL, functional capacity, and life satisfaction were all significantly lower after 12 years in men and women, with the exception of life satisfaction in women. The change in scores for functional capacity from baseline to year 12 was significantly associated with change in life satisfaction; however, the changes in ADL and age at baseline were not. CONCLUSIONS: We observed decreases in ADL, functional capacity, and life satisfaction among SMON patients. Our results suggest that a decrease in life satisfaction can be prevented by maintaining or improving functional capacity.

[Evaluation of neurological symptoms related to hip fracture in a 29-year longitudinal study of subacute myelo-optic-neuropathy (SMON)].

AIM: Hip fracture in elderly people is a major risk factor in the deterioration of activities of daily living (ADL). The aim of this study was to investigate the incidence of hip fractures and the neurological symptoms contributing to hip fracture in patients with subacute myelo-optic-neuropathy (SMON), a drug-induced neurological disease manifesting various symptoms. METHODS: We investigated the incidence of hip fracture in 3,269 SMON patients with 24,187 medical check-ups from 1979 through 2007 by the SMON Research Committee in Japan. Neurological symptoms were evaluated in 80 patients who had undergone clinical examinations within 2 years before the fracture (hip-fracture group: age at examination = 75.7 ± 8.8 years (mean ± SD)), and the control group (160 SMON patients without a history of hip fracture; 76.5 ± 10.4) were matched for age, gender, and duration of illness. Incidence of hip fracture in SMON as well as severity of visual acuity, motor and sensory symptoms, and ADL were investigated. RESULTS: A total 230 hip fractures occurred in 208 patients (6.4%) with a men-to-women ratio of 21 : 187. In comparison with the Japanese general population, SMON patients showed a statistically high incidence of hip fracture in the 50s and 60s age groups in women (p < 0.002 in both), and in those under 40 (p < 0.02) and in their 50s (p < 0.002) in men. In those with neurological symptoms related to gait, the percentage of subjects who could walk with crutches was significantly higher in the hip-fracture group (43.8%) than in the control group (28.1%) (p < 0.05). Analysis of the vibratory sensation revealed that the hip-fracture group showed a significantly higher percentage of severe impairment (51.9%) than the control group (32.0%) (p < 0.025). There were no significant differences in variance between the two groups in other clinical symptoms or ADL. CONCLUSIONS: Impairment of vibration sense, a deep sensation, is more likely to be associated with falling and hip fracture than visual acuity or other neurological symptoms in SMON patients. Those persons with vibration sense disturbance, such as elderly or patients with neurological diseases, should be particularly cautious of falling.

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.

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 Clarke's 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.

[Frequency and clinical characteristics of individuals with presenile dementia in Aichi prefecture].

The aim of this study is to investigate the frequency, causes, and clinical characteristics of individuals with presenile dementia with an age of onset less than 65 years. A staged questionnaire survey was performed among all hospitals and clinics, all faculties of care and welfare services, and all local governmental offices in Aichi prefecture. The response rate of the primary survey was 62.3%, and that of the secondary survey was 90.1%. The number of people with presenile dementia after adjusting for duplicated subjects was 1,092 (569 men, 520 women and 3 of unknown gender). The average age was 60.7 +/- 7.1 (mean +/- SD) years, and age of onset was 55.1 +/- 7.8 years. Vascular dementia (VD) was the most frequent cause in men (42.2%), followed by Alzheimer's disease (AD: 24.8%), frontotemporal dementia (FTD: 4.6%) and Parkinson disease (PD: 3.8%). In women, AD was the most common (45.8%), followed by VD (25.4%), FTD (7.4%) and PD (3.4%). Overall, AD and VD were the most common causes of presenile dementia, followed by FTD and PD. The highest prevalence of presenile dementia was seen in the age range of 60- 64-years-old. This was true for both men and women.

Tongue strength in patients with subacute myelo-optico-neuropathy.

Subacute myelo-optico-neuropathy (SMON) is a neurodegenerative disease that may be caused by overdose or prolonged oral administration of clioquinol. Recently, dysphagia has attracted attention as a complication of SMON. To investigate lingual control in SMON, we examined patients with SMON using assessments of maximum tongue pressure, compared with dysphagia-related diseases, such as sporadic inclusion body myositis (sIBM) and amyotrophic lateral sclerosis (ALS), and healthy volunteer. The mean maximum tongue pressure (Pmax) in patients with SMON was 14.7 ±â€¯5.8 kPa, while it was 33.6 ±â€¯4.4 kPa in the controls. In contrast, the mean Pmax for patients with ALS with or without bulbar involvement was 7.8 ±â€¯2.7 kPa and 34.4 ±â€¯5.7 kPa, respectively, while it was 29.4 ±â€¯8.2 kPa in patients with sIBM. Pmax values correlated with lower limb weakness in SMON patients. Decreases in Pmax may be involved in the development of dysphagia in patients with SMON.

[Siblings with xeroderma pigmentosum group A showing mild cutaneous and various neurological manifestations].

We report siblings with xeroderma pigmentosum group A (XP-A) showing mild cutaneous and late-onset severe neurological manifestations. The elder brother first noticed unstability in walking at 16 years of age. Subsequently slowly progressive mental deterioration developed with cerebellar ataxia, spasticity, sensory disturbance, urinary dysfunction and vocal cord paralysis. His younger sister presented with dysarthria at 18 years of age. She showed manifestations similar to her brother's. Both of them suffered from sensitivity to the sun but no malignant skin tumor. They were diagnosed as XP-A by the measurement of unscheduled DNA synthesis and complementation analysis. Gene analyses revealed compound heterozygote for G-->C substitution at the 3' splicing acceptor site of intron 3 and insertion of 4 bases in exon 6 of XPA gene. It is suggested that transcription-coupled repair is dominantly affected with relative sparing of global genome repair in these siblings.

[An autopsy case of long-course multiple system atrophy (MSA) with remarkable atrophy and numerous NCI in the temporal lobe].

The patient was 66 year-old man with no family history of neurological diseases. At age 51, he showed initial symptom of parkinsonism, and was revealed a cerebellar atrophy by CT at age 52. He was suffered from malignant syndrome followed by renal dysfunction, which needed hemodialysis therapy. At age 54, he admitted to our hospital, when he showed parkinsonism, ataxia and dysautonomia. Neuroimaging study disclosed typical findings of multiple system atrophy (MSA), and dilatation of inferior horn of the lateral ventricle. In the next year, he lost of amburatory function, and showed low cognitive function of 5 scores in HDSR. At age 57, he was tracheostomised because of complete paralysis of the vocal cord abductor muscles. MRI study disclosed marked temporal lobe atrophy. He was complicated with bladder carcinoma, and died of multiple organ failure at age 66. The brain weight was 1,115 g. Gross neuropathological findings were temporal lobe dominant cerebral atrophy and marked pontocerebellar atrophy. Meningitis and sepsis were seen in the cerebrum, and some infarctions in the temporal and frontal lobes. Besides the typical degenerative findings of MSA, remarkable temporal lobe atrophy with enlargement of the inferior horn of lateral ventricle was observed. There were numerous number of neuron containing neuronal inclusion body (NCI) in the hippocampal cortex, dentate fascia and parahippocampal gyrus. In spite of small amount of NFT in the parahippocampal gyrus, there were no se- nile plaque, tau-positive structure except NFT, argyrophilic grain or Pick body. This case was a long-survived MSA with remarkable atrophy of the temporal lobe. The characteristic neuropathological finding was numerous numbers of neurons containing NCI in the cotices arround the inferior horn. Although frontal lobe dominant cerebral lobe atrophy is common in the long-survived MSA cases, extreme temporal lobe atrophy is rare condition. There may be a MSA subtype strongly affecting temporal lobe with numerous NCI.

[Two cases of Duchenne muscular dystrophy complicated with dilated cardiomyopathy and cerebral infarction].

We report two cases of Duchenne muscular dystrophy (DMD) complicated with dilated cardiomyopathy (DCM), who were affected with cerebral infarction. Case 1 suddenly developed dysarthria and right facial weakness at age 21. Cranial CT study disclosed a low density area in the left basal ganglia and internal capsule. Case 2 had a history of transient ischemic attack (TIA) at age 21. Five months after the TIA, he developed right hemiplegia and dysarthria, and a low density area in the corona radiate in left cerebral hemisphere was observed in cranial CT. These two cases showed the radiographic cardiomegaly with cardio thoracic ratio (CTR) of 72.8% and 66.6%, the decreased echocardiographic left ventricular ejection fraction below 20%, and the elevated titer of thrombin-anti-thrombin III complex (TAT) and D-dimer. The autopsy of Case 2 at age 26 disclosed the remarkable degeneration and fibrosis of myocardium and old ischemic lesion in the left cerebral frontal cortex. Despite the negative finding of the emboli in the left heart, cardiogenic cerebral infarction secondary to DCM was strongly suspected in both cases.

Electron microscopic findings of cardiomyopathy with limb girdle muscular dystrophy.

Cardiac involvement in limb girdle muscular dystrophy has considered to be rare. This is the first report showing the electron microscopic findings of dilated cardiomyopathy (DCM) accompanied with limb girdle muscular dystrophy. The findings described in this report indicate that limb girdle muscular dystrophy may be yet another cause of DCM.

[Effect of intermittent positive pressure ventilation on life-span and causes of death in Duchenne muscular dystrophy].

We have been introducing the intermittent positive pressure ventilation (IPPV) therapy in Duchenne muscular dystrophy (DMD) since 1990. Then, the changes of life-span and causes of mortality by IPPV were investigated in this study. The subjects were 157 patients of long-term followed up DMD in our hospital. The Kaplan-Meier's survival curve of 73 IPPV treated patients showed a median survival time of 31.0 years of age, whereas that of 20.4 years in 84 patients not treated by IPPV. The actual mean age of death in 29 IPPV treated patients was 25.68 +/- 5.18 years-old (M +/- SD), which was significantly higher than that in 74 patients with not-IPPV treated of 19.76 +/- 3.47. The IPPV treatment changed the major causes of death; 59.5% to 3.5% for respiratory failure, 12.2% to 37.9% for cardiac failure, and 0% to 10.3% for repiratory trouble. There were certain number of patients who died of repiratory infection, respiratory tract disorder, digestive organ disorders and sudden death. Thus, IPPV therapy is significantly effective for prolongation of life-span in DMD, and it seems to be necessary to establish the treatment strategy for cardiac failure and other potentially fatal complications.

[SMON: toxicity of clioquinol and the status quo].

Subacute myelo-optico-neuropathy (SMON) is a disease characterized by subacute onset of sensory and motor disorders in the lower half of the body and visual impairment preceded by abdominal symptoms. A large number of SMON were observed throughout Japan, and the total number of cases reached nearly 10,000 by 1970. Despite clinical features mimicking infection or multiple sclerosis, SMON was confirmed as being caused by ingestion of clioquinol, an intestinal antibacterial drug, based on extensive epidemiological studies. After the governmental ban on the use of clioquinol in September 1970, there was a dramatic disappearance of new case of SMON. In the 1970s, patients with SMON initiated legal actions against the Government and pharmaceutical companies, and the court ruled that the settlements would be made as health management allowances and lasting medical check-ups. The physical condition of patients with SMON remains severe owing to SMON as well as gerontological complications. The pathological findings in patients with SMON included symmetrical demyelination in the lateral and posterior funiculi of the spinal cord and severe demyelination of the optic nerve in patients with blindness. Although clioquinol may show activity against Alzheimer's disease or malignancy, its toxic effects cause severe irreversible neurological sequelae. Thus, caution must be exercised in the clinical use of clioquinol.

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

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.

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.

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.