Gen Sobue

Nagoya University, Nagoya, Aichi, Japan

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Publications (791)3060.22 Total impact

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    ABSTRACT: The aim of this study is to evaluate the correlation between brain perfusion and cognitive dysfunction in spinocerebellar ataxia type 6 (SCA6) patients. Thirteen genetically confirmed SCA6 patients and 21 age- and education-matched control subjects were subjected to single photon emission computed tomography (SPECT) and neuropsychological tests. Brain perfusion was examined with SPECT analysis, while general cognition, verbal and visual memory, attention, visuospatial ability, language, executive function, depression, and anxiety were examined with the neuropsychological tests. SCA6 patients showed prefrontal hypoperfusion, and impairments of visual memory, verbal fluency, and executive function compared to control subjects. These neuropsychological impairments in SCA6 patients were significantly correlated with a decrease in prefrontal perfusion. This relation was not correlated to other factors, such as age, education and severity of cerebellar ataxia, which are possible relevant factors associated with cognitive performance. SCA6 patients have mild cognitive impairment, and correlating prefrontal hypoperfusion. These results indicate cognitive impairment in SCA6 patients resulting from prefrontal hypoperfusion.
    Journal of the Neurological Sciences 09/2008; 271(1-2):68-74. DOI:10.1016/j.jns.2008.03.018 · 2.26 Impact Factor
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    ABSTRACT: To investigate the current state of education for undergraduates, the subcommittee of the Japanese Society of Neurology for undergraduate education sent a questionnaire on the 2001-version of Model Core Curriculum to the department of neurology in 80 medical universities and their 7 associate medical institutes throughout Japan. Answers were obtained from 56 out of those 87 institutes (64.4%). According to the answers, the Core Curriculum was introduced to the program of undergraduate education in 93% of those 56 universities. For the revision of neurology part in the current Core Curriculum, there are number of requests for improving the description on the neurological examination, list of common symptoms and disorders, and addition of therapeutics. Despite application of the Model Core Curriculum in medical education, the present study disclosed that there were considerable difference in the number and content of the lectures, and the duration of clinical clerkship in neurology ward. These differences of the curriculum and training program depends on not only the number of staffs, but also whether they are working as staffs in a department of neurology or as a small group of neurologists within a department other than neurology.
    Rinsho shinkeigaku = Clinical neurology 09/2008; 48(8):556-62. DOI:10.5692/clinicalneurol.48.556
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    ABSTRACT: Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.
    Journal of the Neurological Sciences 09/2008; 271(1-2):40-6. DOI:10.1016/j.jns.2008.03.013 · 2.26 Impact Factor
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    ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. Because the progression of SBMA is slow, it is plausible to identify biomarkers that monitor disease course for therapeutic development. To verify whether the 6-min walk test (6MWT) is a biomarker of SBMA, we performed the 6MWT in 35 genetically confirmed patients and in 29 age-matched healthy controls. The walk distance covered within 6 min (6MWD) was significantly less in SBMA than it was in controls (323.3 +/- 143.9 m and 637.6 +/- 94.2 m, respectively; P < 0.001). In test-retest analysis, the intraclass correlation coefficient for the 6MWD was high in SBMA patients (r = 0.982). In a 1-year follow-up the 6MWD significantly decreased at a rate of 11.3% per year. Our observations suggest that the 6MWT is a biomarker that can be used to monitor progression of motor impairment in SBMA.
    Muscle & Nerve 08/2008; 38(2):964-71. DOI:10.1002/mus.21077 · 2.31 Impact Factor
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    ABSTRACT: The pathomechanism of sporadic amyotropic lateral sclerosis is not clearly understood, although a proportion of familial amyotropic lateral sclerosis is caused by superoxide dismutase 1 mutations. Theories based on studies of human post-mortem tissue, research on animal models and in vitro work have been proposed for the pathogenesis of amyotropic lateral sclerosis, but the pathogenesis is not the same between sporadic and familial amyotropic lateral sclerosis. Drug candidates were tested using superoxide dismutase 1 mutant mice. Although the candidates were shown to be effective in mice, clinical trials in humans have failed to identify any truly effective pharmacotherapies in sporadic amyotropic lateral sclerosis, with only riluzole providing a modest improvement in survival. Ongoing or planned trials are exploring the value of antiglutamatergic drugs, antioxidants, neurotrophic factors, anti-inflammatory drugs and anti-aggregation drugs. A combination of drugs acting on different mechanisms is needed for effective therapy. Moreover, gene expression profiling and genome-wide association studies, together with inhibitory RNA techniques, are helpful for developing new pharmacotherapeutic strategies including gene therapy. It is also likely that the recently advanced generation of induced pluripotent stem cells will lead to the development of cell therapy for amyotropic lateral sclerosis. In addition to finding effective therapies, research is also needed in order to detect early disease markers since pharmacotherapy is most beneficial when given early in the course of sporadic amyotropic lateral sclerosis.
    Expert Opinion on Pharmacotherapy 08/2008; 9(11):1845-57. DOI:10.1517/14656566.9.11.1845 · 3.09 Impact Factor
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    ABSTRACT: We examined the diagnostic difficulty in thiamine deficiency. We report on two patients with polyneuropathy associated with thiamine deficiency (i.e., beriberi neuropathy) that presented with acute motor symptoms mimicking Guillain-Barré syndrome. The cause of the thiamine deficiency was associated with gastrectomy to treat cancer in a 46-y-old man and with dietary imbalance in a 33-y-old man. The thiamine deficiency was not related to alcohol intake in either patient. In both patients, the upper and lower extremities showed a rapidly progressive weakness over the course of 1 mo. Muscle weakness in the first patient progressed even after admission to the hospital, and urinary retention, Wernicke's encephalopathy, lactic acidosis, paralytic ileus, and heart failure appeared subsequently. Clinical symptoms in both patients showed improvement after initiation of thiamine administration, although some residual deficit remained. Thiamine deficiency must be actively considered as a possible cause of polyneuropathy, and variability in its clinical features should be taken into consideration.
    Nutrition 07/2008; 24(7-8):776-80. DOI:10.1016/j.nut.2008.02.022 · 3.05 Impact Factor
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    ABSTRACT: Polyglutamine diseases are hereditary neurodegenerative disorders caused by an abnormal expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract. To date, nine polyglutamine diseases are known: Huntington's disease (HD), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA) and six forms of spinocerebellar ataxia (SCA). The diseases are inherited in an autosomal dominant fashion except for SBMA, which shows an X-linked pattern of inheritance. Although the causative gene varies with each disorder, polyglutamine diseases share salient genetic features as well as molecular pathogenesis. CAG repeat size correlates well with the age of onset in each disease, shows both somatic and germline instability, and has a strong tendency to further expand in successive generations. Aggregation of the mutant protein followed by the disruption of cellular functions, such as transcription and axonal transport, has been implicated in the etiology of neurodegeneration in polyglutamine diseases. Although animal studies have provided promising therapeutic strategies for polyglutamine diseases, it remains difficult to translate these disease-modifying therapies to the clinic. To optimize "proof of concept", the process for testing candidate therapies in humans, it is of importance to identify biomarkers which can be used as surrogate endpoints in clinical trials for polyglutamine diseases.
    Current Molecular Medicine 06/2008; 8(3):221-34. DOI:10.2174/156652408784221298 · 3.61 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate cognitive impairment in patients with spinocerebellar ataxia type 6 (SCA6) and to verify the role of cerebellar involvement in intellectual abilities. Cognitive function was examined in 18 patients with genetically confirmed SCA6 and in 21 age and education matched controls using a test battery for attention, verbal and visuospatial memory, as well as executive function. Verbal fluency and immediate visual memory task were markedly impaired in SCA6 compared with the control group (p = 0.007, 0.004 and 0.014, respectively). The results of the Rule Shift Cards Test was reduced in patients with SCA6, but the reduction was not significant. These cognitive dysfunctions did not correlated with CAG repeat length, age at onset, ataxic motor dysfunctional scale or depression. Our results demonstrate that specific cognitive deficits occur in patients with SCA6, independent of ataxic motor dysfunction. These deficits may reflect disruption of cortico-cerebellar circuits.
    Journal of neurology, neurosurgery, and psychiatry 06/2008; 79(5):496-9. DOI:10.1136/jnnp.2007.119883 · 5.58 Impact Factor
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    ABSTRACT: Silent brain infarction (SBI) is often detected on MR imaging, however the pathogenesis is still unclear. We aimed to investigate and compare the association of soluble adhesion molecules and C-reactive protein levels with the prevalence of SBI in patients with and without diabetes mellitus. We recruited 130 patients (mean age 59.6 +/- 7.6 yrs) with type 2 diabetes and 130 age- and sex-matched non-diabetic subjects. All subjects underwent head MRI to determine SBI. We measured levels of soluble intercellular adhesion molecule 1(sICAM-1), vascular cell adhesion molecule 1(sVCAM-1), and high sensitivity C-reactive protein (hs-CRP) and evaluated intima-media complex thickness (IMT) in common carotid arteries by ultrasound B-mode imaging. SBI was present in 36 (27.7%) of the diabetic patients and 31 ( 23.8%) of the non-diabetic subjects. Levels of sICAM-1, sVCAM-1 and IMT were all significantly higher in diabetic patients than in non-diabetic subjects, and were significantly increased in both subjects with SBI. IMT was only positively correlated with sVCAM-1 levels in diabetic and non-diabetic subjects. On the other hand, hs-CRP levels were not significantly different in both subjects with and without SBI. In addition, sICAM-1 levels were associated with a significantly higher relative risk for the prevalence of SBI in diabetic patients after multivariate adjustment. Our study suggests that the associations between endothelial dysfunction and presence of SBI may be stronger in diabetic patients than in nondiabetic subjects. In particular, sICAM-1 may play an important role for the pathogenesis of SBI in patients with diabetes mellitus.
    Current neurovascular research 06/2008; 5(2):106-11. DOI:10.2174/156720208784310213 · 2.74 Impact Factor
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    ABSTRACT: We report the case of a 67-year-old man with MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD) with a rapidly progressive clinical course of 5 months. Initial symptoms were progressive memory disturbance and dementia. MRI revealed high signal-intensity lesions on diffusion-weighted images in the bilateral frontal and occipital cortices. Myoclonus and periodic sharp-wave complexes on the electroencephalogram were observed in the early disease stage. The clinical diagnosis was typical sCJD. Neuropathologic examination at autopsy showed widespread, characteristic cerebral neocortical involvement with large confluent vacuole-type spongiform change. Spongiform degeneration was also evident in the striatum and medial thalamus. In the cerebellar cortex, slight depletion of Purkinje neurons was evident without spongiform change in the molecular layer or apparent neuron loss in the granule cell layer. The inferior olivary nucleus showed slight hypertrophic astrocytosis without neuron loss. Prion protein (PrP) immunostaining showed widespread, characteristic perivacuolar-type PrP deposits with irregular plaque-like PrP deposits in the cerebral neocortex, striatum and medial thalamus. We believe this patient showed early-stage cerebral cortical pathology of MM2-cortical-type sCJD, which may provide clues regarding the pathologic progression of this rare sCJD subtype. Although MM2-cortical-type sCJD generally shows slow progression without myoclonus or periodic sharp-wave complexes, the present patient showed a rapidly progressive clinical course similar to that of MM1-type sCJD.
    Neuropathology 05/2008; 28(6):645-51. DOI:10.1111/j.1440-1789.2008.00904.x · 1.80 Impact Factor
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    ABSTRACT: We evaluated comprehensive neuropsychological tests and regional brain blood flow to compare cognitive dysfunction between two types of multiple system atrophy: predominant cerebellar ataxia (MSA-C) and predominant parkinsonism (MSA-P). Twenty-one patients with MSA-C, 14 patients with MSA-P, and 21 age- and education-matched control subjects were subjected to neuropsychological tests and SPECT. The neuropsychological tests examined general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety, while SPECT analysis examined brain perfusion. Patients with MSA-P showed severe involvement of visuospatial and constructional function, verbal fluency, and executive function compared with control subjects. Patients with MSA-C showed involvement only in visuospatial and constructional function compared with control subjects and a milder degree of involvement compared with patients with MSA-P. Patients with MSA-P tended toward a wide and severe impairment in cognitive function compared with patients with MSA-C. In addition, neuropsychological impairment in patients with MSA-P was significantly correlated with a decrease in prefrontal perfusion. This significant relation was not correlated to other factors such as age, education, and severity of cerebellar ataxia and parkinsonism, which are relevant factors associated with cognitive performance. Patients with multiple system atrophy-parkinsonism show more severe and more widespread cognitive dysfunctions than patients with multiple system atrophy-cerebellar ataxia. Our results also indicate that cognitive dysfunction in patients with multiple system atrophy-parkinsonism may be associated with prefrontal involvement.
    Neurology 05/2008; 70(16 Pt 2):1390-6. DOI:10.1212/01.wnl.0000310413.04462.6a · 8.30 Impact Factor
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    ABSTRACT: To reveal characteristic clinicopathological correlates of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. The clinical features of 22 patients with POEMS syndrome were investigated and correlated with the histopathological features of sural nerves and serum cytokine profiles. More than half of the patients complained of pain in the lower extremities, which is closely related to hyperalgesia. Assessment of the total nerve fibre population using complete transverse sural nerve cross-sections, excluding the marked enlargement of endoneurial areas due to intrafascicular oedema, showed that myelinated fibres, especially small myelinated fibres, were reduced, whereas unmyelinated fibres were preserved. Uncompacted myelin lamellae and segmental demyelination were seen more frequently in the small, rather than the large, myelinated fibres. The presence of hyperalgesia was electrophysiologically associated with a reduction of sensory nerve action potentials in the sural nerve (p<0.05) and histopathologically associated with myelinated fibre loss (p<0.01). Serum levels of proinflammatory cytokines (interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha), but not their soluble receptors, were significantly elevated in patients with hyperalgesia (p<0.05-0.01). Hyperalgesia seen in patients with POEMS syndrome is closely related with a reduction in the myelinated, but not unmyelinated, fibre population. Elevation of proinflammatory cytokines is also correlated with hyperalgesia. The painful symptoms in POEMS syndrome may be generated by well-preserved unmyelinated C-fibres due to the lack of inhibitory myelinated A-fibres, along with cytokine sensitisation.
    Journal of neurology, neurosurgery, and psychiatry 04/2008; 79(10):1171-9. DOI:10.1136/jnnp.2007.135681 · 5.58 Impact Factor
  • Haruki Koike, Gen Sobue
    Journal of neurology, neurosurgery, and psychiatry 03/2008; 79(2):113. DOI:10.1136/jnnp.2007.135137 · 5.58 Impact Factor
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    ABSTRACT: We present five cases of dura mater-associated Creutzfeldt-Jakob disease (dura-CJD) that were analyzed clinicopathologically and review previous reports. The average age at dura mater transplantation was 54.4 +/- 7.3 years, and the average age at CJD onset was 66.0 +/- 8.2 years, with an average latency period of 11.6 +/- 1.1 years. The average age at death was 67.6 +/- 8.7 years, with an average CJD disease duration of 16.8 +/- 10.4 months. Symptoms of CJD onset in four patients who received dura mater transplantation below the cerebellar tent reflected cerebellar or brainstem dysfunction, whereas symptoms of one patient who received transplantation above the cerebellar tent reflected cerebral cortical involvement. All patients showed rapidly progressive cognitive impairment, and both periodic sharp-wave complexes on electroencephalogram and myoclonus were observed in the early disease stage. Neuropathologic evaluation showed one case of subacute spongiform encephalopathy and four cases of panencephalopathic-type CJD. Widespread cerebral neocortical, subcortical gray matter and cerebellar cortical involvement were observed to varying degrees, and severity tended to be associated with CJD disease duration. There were no instances of kuru plaques or florid plaques. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition. No differences between our dura-CJD cases and typical cases of sporadic CJD were found with respect to clinicopathologic findings, except history of dura mater transplantation. Although a specific association between the dura mater graft site and neuropathologic observations was not evaluated in the present study, the initial symptoms appear to be closely related to the graft site, indicating a direct transmission of CJD from the graft site to the adjacent brain.
    Neuropathology 03/2008; 28(1):51-61. DOI:10.1111/j.1440-1789.2007.00847.x · 1.80 Impact Factor
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    ABSTRACT: This study evaluated pupillary postganglionic autonomic dysfunction and its relationship to visual disturbance in idiopathic Parkinson's disease (PD). Pupillary sensitivity was examined in relation to a parasympathomimetic agent [0.05% pilocarpine hydrochloride (PL)] and to a sympathomimetic agent [0.02% dipivefrine hydrochloride (DPE)] using infrared pupillography in 40 PD patients and 17 age-matched controls. Visual disturbances were evaluated as well, including blurring, photophobia, night blindness and involuntary eyelid closure in response to light. Pupillary supersensitivity to PL and DPE and their relation to visual disturbances were found to be significantly greater in PD patients than in controls (22.3 +/- 15.1 vs. 10.4 +/- 11.4%, P < 0.005, and14.5 +/- 14.5 vs. 4.9 +/- 8.7%, P < 0.01, respectively). In addition, pupillary sympathetic supersensitivity did not correlate with a reduction of 123I-metaiodobenzylguanidine (MIBG) cardiac accumulation. Patients with PD reported more blurred vision (P < 0.001) and involuntary eyelid closure in response to light (P < 0.05) than controls. Patients with supersensitivity to both PL and DPE complained more often of blurred vision than patients without supersensitivity (P < 0.05). Pupillary sensitivity to PL correlated significantly with a summed score for visual disturbance (P < 0.05, r = 0.417), but DPE sensitivity did not. PD patients have both parasympathetic and sympathetic postganglionic impairments affecting the pupil. Our findings demonstrate that parasympathetic dysfunction contributes significantly to visual disturbance in PD.
    Clinical Autonomic Research 02/2008; 18(1):20-7. DOI:10.1007/s10286-008-0453-4 · 1.86 Impact Factor
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    ABSTRACT: This study was to clarify the neuropathological findings of non-herpetic acute limbic encephalitis (NHALE) and so-called acute juvenile female non-herpetic encephalitis (AJFNHE). We examined three rare autopsied cases consisting of probable one NHALE and two AJFNHLE. For comparison, we also studied 10 autopsied cases of hippocampal sclerosis mainly caused by anoxia. In NHALE, neuronal loss with gliosis and microglia/macrophage infiltrations were mainly seen in the CA1 areas in the hippocampus. However, there were no apparent anoxic neuronal changes in the remaining neurons in the CA1, and astrocyte proliferations and microglia/macrophage infiltrations were also observed in the claustrum, while these were mildly present in the basal ganglia. In AJFNHE, pathological findings differed from those of NHALE with regard of the absence of limited pathology in the limbic system, microglia/macrophages widely infiltrated the brain including the hippocampal areas and mild lymphocytic infiltrations were observed in the subarachnoid spaces as well as in the parenchyma. The pathomechanism of NHALE and AJFNHE is obscure and autoimmune theory is proposed, however we must collect and examine many autopsied cases in order to clarify the pathomechanism.
    Internal Medicine 02/2008; 47(4):231-6. DOI:10.2169/internalmedicine.47.0547 · 0.97 Impact Factor
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    ABSTRACT: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates in Japan. The prevalence rate per 100 000 was 1.61 in the total population; 2.01 in males and 1.23 in females. The age dependent prevalence rates were 0.23 in juveniles (<15 years old), 1.50 in young adults (15-55 years) and 2.31 in elderly adults (>55 years). The sex and age dependent prevalence rates were 0.22 in males and 0.24 in females in juveniles, 1.81 in males and 1.19 in females in young adults, and 3.12 in males and 1.64 in females in elderly adults. The annual incidence rate per 100 000 was 0.48 in the total population, 0.58 in males and 0.38 in females. The age dependent incidence rate was 0.06 in juveniles, 0.40 in young adults and 0.73 in elderly adults. The sex and age dependent incidence rate was 0.05 in males and 0.08 in females in juveniles, 0.50 in males and 0.30 in females in young adults, and 0.93 in males and 0.58 in females in elderly adults. Both the prevalence and incidence rates were very similar throughout the eight geographical areas studied, from the northern to the southern parts of Japan. The prevalence and incidence rates were similar to those reported in the Caucasian population. The pathogenic background is suggested to be common throughout the different races and geographic areas, while gender and age effects should be taken into account in the pathogenesis of CIDP.
    Journal of neurology, neurosurgery, and psychiatry 02/2008; 79(9):1040-3. DOI:10.1136/jnnp.2007.128132 · 5.58 Impact Factor
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    ABSTRACT: We describe a sleep attack, which was induced by taking excessive levodopa and pergolide, in a 73-year-old woman with Parkinson's disease. At the onset of the sleep attack, her head suddenly sagged and sometimes hit the table, but she did not notice these symptoms. Her family noticed that this sleep attack occurred when she began to speak slowly. Her family recorded this attack with a video camera. This sleep attack resolved with control of her medication. This is the first report of video images of a sleep attack due to excessive levodopa and a dopamine agonist.
    Movement Disorders 01/2008; 23(2):288-90. DOI:10.1002/mds.21830 · 5.63 Impact Factor
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    ABSTRACT: We investigated the correlation between results of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and those of cardiovascular autonomic function tests in patients with Parkinson's disease (PD). 123I-MIBG myocardial scintigraphy and a 5-minute standing test were performed in 50 patients with PD and in 19 control subjects. The value of the basal plasma noradrenaline (NA) level was used as an index of basal sympathetic nerve activity, and %NA was used to assess the response of sympathetic nerve activity. In addition, the parameters of DeltaBP and DeltaHR were evaluated to assess the autonomic response of the cardiovascular system. A mild, but significant correlation was observed between the myocardium to mediastinum (H/M) ratio and the values of the plasma NA baseline (r = 0.35, p < 0.05 in early image, r = 0.29, p < 0.05 in delay image). No significant correlation was observed between the H/M ratio and the other parameters (%NA, DeltaBP, DeltaHR). These results suggest that 123I-MIBG myocardial scintigraphy may be associated with the basal sympathetic nerve activity, but not with autonomic nervous response of the cardiovascular system in patients with PD.
    Rinsho shinkeigaku = Clinical neurology 01/2008; 48(1):56-9. DOI:10.5692/clinicalneurol.48.56
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    ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, lower motor neuron disease caused by an aberrant elongation of a CAG repeat in the androgen receptor (AR) gene. The main symptoms are weakness and atrophy of bulbar, facial and limb muscles, but sensory disturbances are frequently found in SBMA patients. Motor symptoms have been attributed to the accumulation of mutant AR in the nucleus of lower motor neurons, which is more profound in patients with a longer CAG repeat. We examined nerve conduction properties including F-waves in a total of 106 patients with genetically confirmed SBMA (mean age at data collection = 53.8 years; range = 31-75 years) and 85 control subjects. Motor conduction velocities (MCV), compound muscle action potentials (CMAP), sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) were significantly decreased in all nerves examined in the SBMA patients compared with that in the normal controls, indicating that axonal degeneration is the primary process in both motor and sensory nerves. More profound abnormalities were observed in the nerves of the upper limbs than in those of the lower limbs. F-waves in the median nerve were absent in 30 of 106 cases (28.3%), but no cases of absent F-waves were observed in the tibial nerve. From an analysis of the relationship between CMAPs and SNAPs, patients were identified with different electrophysiological phenotypes: motor-dominant, sensory-dominant and non-dominant phenotypes. The CAG repeat size and the age at onset were significantly different among the patients with motor- and sensory-dominant phenotypes, indicating that a longer CAG repeat is more closely linked to the motor-dominant phenotype and a shorter CAG repeat is more closely linked to the sensory-dominant phenotype. Furthermore, when we classified the patients by CAG repeat size, CMAP values showed a tendency to be decreased in patients with a longer CAG repeat (> or =47), while SNAPs were significantly decreased in patients with a shorter CAG repeat (<47). In addition, we found that the frequency of aggregation in the sensory neuron cytoplasm tended to inversely correlate with the CAG repeat size in the autopsy study, supporting the view that the CAG repeat size differentially correlates with motor- and sensory-dominant phenotypes. In conclusion, our results suggest that there are unequivocal electrophysiological phenotypes influenced by CAG repeat size in SBMA.
    Brain 01/2008; 131(Pt 1):229-39. DOI:10.1093/brain/awm289 · 10.23 Impact Factor

Publication Stats

15k Citations
3,060.22 Total Impact Points


  • 1996–2015
    • Nagoya University
      • • Division of Neurology
      • • Institute for Advanced Research (IAR)
      Nagoya, Aichi, Japan
  • 2012–2013
    • Japan Science and Technology Agency (JST)
      Edo, Tōkyō, Japan
    • Chubu Rosai Hospital
      Nagoya, Aichi, Japan
  • 1995–2013
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
  • 1993–2013
    • Kyoto Daini Red Cross Hospital
      Kioto, Kyōto, Japan
  • 2009–2010
    • Kumamoto University
      • Graduate School of Pharmaceutical Sciences
      Kumamoto-shi, Kumamoto Prefecture, Japan
  • 2007
    • Dokkyo Medical University
      • Department of Neurology
      Totigi, Tochigi, Japan
  • 1999–2007
    • Fujita Health University
      Nagoya, Aichi, Japan
  • 1987–2006
    • Aichi Medical University
      • • Division of Internal Medicine
      • • Institute for Medical Science of Aging
      • • Department of Neurology
      Okazaki, Aichi, Japan
  • 2005
    • Hirosaki University
      Khirosaki, Aomori, Japan
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 2004
    • Yamagata University
      Ямагата, Yamagata, Japan
  • 2003
    • Yokkaichi Municipal Hospital
      Yokkaiti, Mie, Japan
    • Kanto Rosai Hospital
      Kawasaki Si, Kanagawa, Japan
  • 2002
    • Kasugai Municipal Hospital
      Касугай, Aichi, Japan
  • 1999–2002
    • Shinshu University
      Shonai, Nagano, Japan
  • 2001
    • Tottori University
      TTJ, Tottori, Japan
    • Kagawa University
      Takamatu, Kagawa, Japan
  • 2000
    • Nara Institute of Science and Technology
      Ikuma, Nara, Japan
    • Tachikawa Hospital
      Edo, Tōkyō, Japan
  • 1997–2000
    • Tokai Central Hospital
      Tokitsu-chō, Gifu, Japan
  • 1998
    • Social Insurance Chukyo Hospital
      Nagoya, Aichi, Japan
  • 1989
    • University of Shizuoka
      • Department of Biochemistry
      Sizuoka, Shizuoka, Japan
  • 1984–1988
    • The Children's Hospital of Philadelphia
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
  • 1984–1987
    • University of Pennsylvania
      • Department of Neurology
      Philadelphia, PA, United States
  • 1982
    • Nagoya City University
      Nagoya, Aichi, Japan