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Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant cerebellar ataxia commonly observed in Japan. However, few neuropathological examinations have been conducted. Here we report the case of a 76-year-old Japanese male SCA31 patient. He noticed dysarthria and difficulty walking at 65 years old. His symptoms subsequently deteriorated, although he could still walk with assistance at 70 years. At 73 years, when he could no longer walk, he was admitted to our hospital. He showed severe limb and truncal ataxia. His father and older brother had shown the same symptoms. Brain magnetic resonance imaging showed cerebellar atrophy of the anterior lobe and white matter hyperintensities. He was diagnosed with SCA31 by genetic analysis. Gradually, his cognitive functions and ability to communicate declined. He died of respiratory failure at the age of 76. Neuropathological examination revealed severe Purkinje cell loss that was accentuated in the anterior lobe of the cerebellum. Furthermore, the remaining Purkinje cells showed abnormal processes (that is, halo-like amorphous materials), as has been reported previously. Severe deposition of hyperphosphorylated tau-positive neurites, many senile plaques and amyloid angiopathy were observed in the neocortex. Our findings suggest that in SCA31, accelerated tau and amyloid pathology in the neocortex might induce dementia at the terminal stage.

Background and purpose: We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients. Methods: Fifty-eight MSA patients were recruited in our institution between April 1996 and December 2006 and investigated. Results: Of 58 patients, 10 were diagnosed with dementia. There were no significant differences in age at onset, gender, duration of disease, or severity of cerebellar dysfunction between patients with and without dementia. The early and delayed heart to mediastinum (H/M) ratios obtained with 123I-metaidobenylguanidine (MIBG) cardiac scintigraphy were significantly decreased in patients with dementia compared with those without dementia. Of the 10 patients with dementia, three were found to have cognitive decline that preceded onset of motor symptoms. White matter lesions were evident in these patients, whilst frontal atrophy was prominent in patients whose cognitive decline was preceded by onset of motor symptoms. Conclusions: Dementia in patients with MSA may be more common than previously thought, furthermore, we speculate that clinical features of dementia in these patients might be heterogeneous.

This study examined the diagnostic value of cerebrospinal fluid (CSF) markers and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD).CSF levels of amyloid beta1-42 (Abeta42) and 181-Thr phosphorylated tau (p-tau) were measured using enzyme linked immunosorbent assay (ELISA) kits. (123)I-MIBG cardiac scintigraphy was performed in patients with AD and DLB, and control (CTL) subjects.Increased CSF levels of p-tau in AD were found compared to DLB patients and CTL subjects (P0.01), but there was no significant difference in CSF levels of Abeta42 between AD and DLB patients. The early and delayed heart to mediastinum (H/M) ratios of (123)I-MIBG cardiac scintigraphy were significantly decreased in patients with DLB compared to AD patients and CTL subjects (P0.01). The receiver operating characteristic (ROC) analysis revealed that the diagnostic value of (123)I-MIBG cardiac scintigraphy was superior to that of CSF markers.(123)I-MIBG cardiac scintigraphy may be useful for discriminating between DLB and AD.

Objective – To assess hallucinations in Parkinson’s disease (PD), we developed a novel practical rating scale that evaluates five items including variety, frequency, and severity of hallucinations, caregiver burden levels, and psychiatric status at nighttime. Methods – Forty-one PD patients and their caregivers were examined regarding the status of the hallucinations associated with PD. Results – As a measure of internal consistency, the Tottori University Hallucination Rating Scale (TUHARS) has a Cronbach’s α of 0.88. Mini-Mental State Examination (MMSE) and Hoehn–Yahr stage were associated with the TUHARS scores in a multivariate regression analysis. Visual hallucinations are the most common. However, half of the patients who reported visual hallucinations also had other hallucinations. The scale scores in the PD patients with dementia (PDD) group were significantly greater than in the PD patients without dementia (PDnD) group. Conclusions – TUHARS appears to be a suitable and easily administered instrument for assessment of hallucinations in PD. PD patients experienced various kinds of hallucinations. Hallucinations may have a close relationship with cognitive decline in PD patients.

The pathogenic events that lead to amyotrophic lateral sclerosis (ALS) have not been elucidated. We previously described familial amyotrophic lateral sclerosis (FALS) caused by a Leu126delTT mutation in the Cu/Zn superoxide dismutase gene (SOD1) and have produced transgenic mice (TgM) carrying the same mutation (SOD1(L126delTT) TgM), which exhibited distinct ALS-like motor symptoms and pathological findings. In this study, we analyzed gene expression in the spinal cord of SOD1(L126delTT) TgM by cDNA microarray. Eleven genes were upregulated and two genes downregulated in pre-symptomatic TgM. In post-symptomatic TgM, 54 genes were upregulated and four genes downregulated. We performed real-time polymerase chain reaction (PCR) analysis of 10 of the 54 upregulated genes in the post-symptomatic TgM. The results of real-time PCR were consistent with those obtained by microarray for micro-crystallin (Crym), heat shock protein 1 (Hspb1/HSP27), serine proteinase inhibitor clade A member 3N (Serpina3n), complement component 1q subcomponent beta polypeptide (C1qb), cathepsin H (Ctsh) and polyadenylate binding protein-interacting protein 1 (Paip1). In immunohistochemical analysis, Hsbp1/HSP27 and Ctsh expression levels were increased in reactive astrocytes at the ventral horn of the spinal cord in post-symptomatic TgM, as were Crym, some of Ctsh and Paip1 in microglial cells. Increased expression of those genes was not observed in the control mice. These four genes may be related to the pathogenesis of FALS, especially with regard to the progression of reactive astrocytes and the inflammatory response of microglial cells.

Background Multidetector computed tomography angiography (MDCTA) is useful to inspect cardiovascular pathologic changes with minimal invasiveness. Here we evaluated the usefulness of MDCTA to determine the cause of acute multiple brain infarction (AMBI). Methods AMBI was defined as multiple recent infarcts demonstrated on diffusion-weighted imaging. A new infarction within 2 weeks from the last was also considered an AMBI. Results Between January 2012 and December 2013, 967 patients were diagnosed with acute brain infarction and 138 (14.3%) with AMBI. Among them, 57 (39 men and 18 women; age, 38-93 years) were examined by MDCTA using the dual-phase method. All images were diagnostic, even if patients found it difficult to hold their breath. Fifteen patients (26.3%) were diagnosed with patent foramen ovale (PFO). Two had complications of atrial fibrillation (AF), necessitating anticoagulant therapy (ACT). Four had both PFO and severe aortic atherosclerotic plaque formation, necessitating single antiplatelet therapy (APT) and/or ACT. Fifteen patients (26.3%) developed complicated arterial plaques around the aortic arch and were administered single or dual APT and/or ACT, except 1 patient with a history of multiple cerebral bleeding. Nine patients had pre-existing AF. Furthermore, ACT was initiated for 2 other patients with thrombus or circulatory stasis in the left atrial appendage despite normal electrocardiographic findings. Two other patients were diagnosed with advanced cancer, which was considered Trousseau syndrome. The cause of AMBI was determined in 36 (63.2%) patients. Conclusions MDCTA is a useful and less invasive method to identify the cause of embolic infarction.

Background Uptake of 123 I-labeled meta-iodobenzylguanidine (MIBG) in myocardial scintigrams has been shown to be as low in patients with idiopathic RBD as in Parkinson’s disease (PD) patients. Aim for study To clarify whether the existence of RBD accelerates autonomic dysfunction in PD, we investigated the association between MIBG scintigraphic findings and RBD measures among non-dementia PD patients. Subjects & methods We conducted clinical interviews to assess REM sleep behavior disorder (RBD) symptoms, and performed polysomnograms (PSG) recordings and MIBG scintigrams on 49 PD patients. The patients were divided into three groups (PD with clinical RBD, PD with subclinical RBD, and PD with normal REM sleep). Results PD patients with clinical RBD had reduced MIBG uptake as determined by heart-to-mediastinum ratios of the delayed image compared to those with subclinical RBD and those with normal REM sleep. Multiple linear regression analysis revealed that only the existence of RBD symptoms was significantly associated with reduced MIBG uptake among PD patients without dementia after adjusting for demographic and PD symptom-related variables. Conclusion PD patients with clinical RBD might suffer from a wider α-synuclein pathology, including reduced cardiac sympathetic ganglia function as reflected by a lowered MIBG uptake.

Background: With the striking increase in the number of elderly people in Japan, dementia has not only become a medical but also a social issue. Methods: We studied the prevalence of dementing disorders in a rural island town of Japan (Ama-cho), using a door-to-door 2-phase design. Results: Of the 120 persons screened as having cognitive impairment, 104 people were diagnosed as having dementia. The prevalence (cases/100 persons aged 65 years and older) was 11.0 for all types of dementia, 7.0 for Alzheimer’s disease, 1.7 for vascular dementia, 0.53 for dementia with Lewy bodies, 0.74 for Parkinson’s disease dementia, 0.21 for progressive supranuclear palsy, 0.11 for frontotemporal lobar degeneration and 0.74 for other dementia. The overall prevalence was higher in women for Alzheimer’s disease and Parkinson’s disease dementia, and in men, for vascular dementia and dementia with Lewy bodies. Conclusion: We confirmed the overall prevalence of dementia in the elderly population aged 65 years and older to be 11.0. This finding is higher compared with previous reports in Japan.

We investigated the time course of ultrastructural changes of mitochondria in the spinal cord of homozygotes of Leu126TTdel SOD1 (superoxide dismutase 1) with FLAG (signal sequence at the C-terminal protein) transgenic mice (DF-homo). Non-Tg mice and wild-type human SOD1 with FLAG epitope transgenic mice (WF) were investigated as controls for non-onset Tg mice. Expansion and vacuolation of the mitochondrial matrix was exhibited in motor neurons in the anterior horns of DF-homo Tg mice at the presymptomatic stage. Such mitochondrial degeneration became severe at the postsymptomatic stage. In contrast, expansion of the mitochondrial inner-membrane space was not evident even at the terminal stage. Microvacuoles of cytoplasm and fibrillar inclusions were rarely shown from the early symptomatic stage. WF mice showed expansion and vacuolation of the mitochondrial inner membrane space at old age. Non-Tgs showed no obvious change in mitochondria. Gold-labeled human SOD1 immunoreactivity showed small amount of gold deposits in the vacuolated mitochondria. These results suggest that the expansion and vacuolation of mitochondrial matrix in the spinal cord of DF-homo transgenic mice is the first pathological change, but that it is not directly caused by the aggregation of an abnormal human SOD1 protein in intermembrane space of mitochondria.

Objective – We investigated executive function in Parkinson’s disease (PD) patients, and focused on executive dysfunction in PD with hallucinations, but without dementia. Methods – PD patients were classified by cognitive or neuropsychotic status as PD group, PD with vivid dreaming group, PD with hallucinations group and Parkinson’s disease dementia (PDD) group. Psychomotor speed tests, the Stroop test, a verbal fluency test and the Self-rating Depression Scale were performed. Results – The PDD group showed poorer scores in every test compared with the PD group. The PD with hallucinations group showed results similar to those of the PDD group, while the PD with vivid dreaming group was similar to the PD group. Conclusions – The study suggests that PD patients with hallucinations, not extensive enough to qualify as dementia, already have executive dysfunction similar to that seen in PDD patients. Executive dysfunction may be an important substrate for hallucinations even when dementia is not yet apparent.

Objectives – In order to explore factors associated with the development of dementia in Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan. Results – There were 208 patients diagnosed as having PD and 39 patients diagnosed with DLB in this study. Of the patients with PD, 67 (32%) developed dementia and only five PD+ patients were considered to have cognitive impairment attributable to Alzheimer’s disease (AD) or vascular dementia (VaD). Fifty-four (81%) PDD patients had visual hallucinations (VH) with or without cognitive fluctuation. The onset age of parkinsonian motor symptoms of patients with PD dementia (PDD) did not differ from that of PD patients without dementia. There was a significant inverse correlation between the onset age of motor symptoms in PD and the onset of their dementia in PDD. Seventy-five (36%) patients with PD had experienced VH and most of the PDD patients had experienced VH within 1 year before or after diagnosis of PDD. Conclusions – These results indicate that aging and VH are important factors associated with dementia in PD.

Background Postganglionic cardiac sympathetic denervation is evident in patients with Parkinson’s disease (PD) and iodine-123 metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy has proven to be a useful tool for diagnosis of PD. Objective To elucidate the factors associated with severity of cardiac sympathetic nerve dysfunction in PD patients. Methods We investigated 95 PD patients hospitalized in the Department of Neurology at Tottori University Hospital. 123I-MIBG cardiac scintigraphy was performed on each patient and the early and delayed heart to mediastinum (H/M) ratios and washout rate (WR) of 123I-MIBG cardiac scintigraphy were calculated. Independent predictive variables for parameters of 123I-MIBG cardiac scintigraphy were analyzed by multivariate regression analysis. Results Multivariate regression analysis revealed that the presence of visual hallucinations (VH) and the patient’s age at the time of evaluation independently predicted the early or delayed H/M ratio. Analysis of covariance, adjusted for the age of the patients as covariates, revealed that the early and delayed H/M ratios of PD patients with VH but no dementia, as well as PD patients with dementia were significantly lower than the ratios in PD patients with no VH or dementia. Conclusion Cardiac sympathetic dysfunction may be associated with the presence of VH in PD patients.