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.

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.

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.

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.

[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.

[Quantitative and qualitative analyses for characteristics of the clock drawing in Alzheimer's disease].

We analyzed the results of the clock drawing test (CDT) in patients with Alzheimer's disease (AD) by quantitative and qualitative methods to evaluate its significance for cognitive function screening. We administered the CDT and mini-mental state examination (MMSE) to a total of 156 AD patients, and CDT performance was scored quantitatively in accordance with the method by Freedman, while the CDT error types were qualitatively classified by Rouleau's method. We divided AD patients into three groups by their MMSE total score (A: 23 ≤, B: 18~22, C: ≤ 17). The mean total scores of CDT and MMSE in AD were 11.5 ± 3.4 and 19.8 ± 4.7, respectively, and the total CDT scores showed significant positive correlation with the total MMSE scores (r = 0.450). Fewer than 80% of subjects drew the clock correctly for 8 out of 15 sub-items, and fewer were able to correctly draw clock hands than could correctly draw numbers, contour or a center. In analysis of CDT qualitative error types, the most common error types were spatial and/or planning deficit (SPD) (28.2%), and conceptual deficit (CD) (23.7%), which suggested visuospatial impairments and semantic impairments play essential roles in AD patients' poor clock drawings. The frequency of CD and SPD error types significantly increased as severity of cognitive function worsened (p < 0.001, p < 0.05, respectively), and those of stimulus-bound response and perseveration had tendency to increase as severity of cognitive function. The present study suggests that CDT is a useful screening method not only for the impairment of cognitive function and the severity of cognitive dysfunction, but also for identification of specific cognitive function impairments in AD patients.

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.

[Complete atrioventricular block in Duchenne muscular dystrophy].

We report a case of complete atrioventricular (AV) block in a 40-year-old patient with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required mechanical ventilation, his cardiac involvement was mild. He had the deletion of exon 45-52 in the dystrophin gene. He underwent transient complete AV block and came to require pacemaker implantation due to recurrence of complete AV block ten days after the first attack. Electrophysiological study revealed mild prolonged AH and HV interval. Although DMD patients with AV block have been rarely reported so far, attention should be paid to AV block for patients who prolonged their lives.

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.

Decreased resting energy expenditure in patients with Duchenne muscular dystrophy.

BACKGROUND: Skeletal muscle metabolism is a major determinant of resting energy expenditure (REE). Although the severe muscle loss that characterizes Duchenne muscular dystrophy (DMD) may alter REE, this has not been extensively investigated. METHODS: We studied REE in 77 patients with DMD ranging in age from 10 to 37 years using a portable indirect calorimeter, together with several clinical parameters (age, height, body weight (BW), body mass index (BMI), vital capacity (VC), creatine kinase, creatinine, albumin, cholinesterase, prealbumin), and assessed their influence on REE. In addition, in 12 patients maintaining a stable body weight, the ratio of energy intake to REE was calculated and defined as an alternative index for the physical activity level (aPAL). RESULTS: REE (kcal/day, mean±SD) in DMD patients was 1123 (10-11 years), 1186±188 (12-14 years), 1146±214 (15-17 years), 1006±136 (18-29 years) and 1023±97 (≥30 years), each of these values being significantly lower than the corresponding control (p<0.0001). VC (p<0.001) was the parameter most strongly associated with REE, followed by BMI (p<0.01) and BW (p<0.05). The calculated aPAL values were 1.61 (10-11 years), 1.19 (12-14 years), 1.16 (15-17 years), and 1.57 (18-29 years). CONCLUSION: The REE in DMD patients was significantly lower than the normal value in every age group, and strongly associated with VC. Both the low REE and PAL values during the early teens, resulting in a low energy requirement, might be related to the obesity that frequently occurs in this age group. In contrast, the high PAL value in the late stage of the disease, possibly due to the presence of respiratory failure, may lead to a high energy requirement, and thus become one of the risk factors for development of malnutrition.

[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.

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.

[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.

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.

[A case of multiple sclerosis with alien hand (diagonistic dyspraxia)].

In this paper, we describe a case of mutiple sclerosis (MS) with diagonistic dyspraxia and the callosal lesions in MRI. The patient was a 54-year-old woman with 12 year-history of suffering from MS. Her clinical symptoms were left alien hand, mild euphoria, right blindness, left visual deficit (0.06), mild weakness of right upper limb, complete paraplegia of lower limbs, total sensory deficit below middle sternal level and neurogenic bladder. She was right-handed person and her alien hand was such a manner; when she intended to use spoon with right hand, her left hand aimlessly began to hold and release a cup or dish. Then, she was diagnosed as diagnostic dyspraxia. Neuropsychological examinations disclosed left hemispheric dysfunction including left hand agraphia and disconnection of the callosum. MRI showed patchy lesions in the callosum, right optic radiation, both side thalamus (left > right), left cerebral peduncle, and spinal cord of cervical to the thoracal portion. Although the functional disorders and the radiological atrophy of the callosum, the clinical manifestation of the callosal disconnection in MS cases has been scarcely reported, and this case seems to be a quite rare condition to be described.

[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.

[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.