Clinical assessment and prevalence of parkinsonism in Japanese elderly people.

BACKGROUND: Parkinsonism is often observed in the elderly. To clarify the prevalence of parkinsonism-associated diseases and conditions, we conducted a population-based study in a rural island town in western Japan, Ama-cho. METHODS: Participants included 924 subjects aged 65 years or older residing in the town. Between 2008 and 2011, participants were assessed via standardized neurological examination scales, and Brain MRIs were carried out in 2010. Based on the results of assessment using the modified Unified Parkinson's Disease Rating Scale and a standardized neurological examination, participants were diagnosed as having parkinsonism or mild parkinsonian signs (MPS), or as displaying normal motor conditions (M-normal). RESULTS: Of the 729 participants screened, 70 subjects were diagnosed as having parkinsonism, corresponding to a crude prevalence rate of 9.6% (95% CI, 7.9-11.3%), while 167 MPS subjects (22.9%) and 492 subjects experiencing M-normal (67.5%) were observed. Parkinsonism was found in association with various diseases such as Vascular parkinsonism, Lewy body disease, Alzheimer's disease (AD), and idiopathic normal-pressure hydrocephalus. Among the subjects with dementia, the proportion with parkinsonism was higher in the non-AD dementia group. CONCLUSION(S): Parkinsonism occurs in association with several diseases in elderly people. Parkinsonism was also found to be commonly associated with cognitive impairment.

Depression and cognitive impairment in patients with mild parkinsonian signs.

OBJECTIVES: Mild parkinsonian signs (MPS) are reported to be associated with increased risk of dementia, Parkinson's disease, parkinsonism, and vascular lesions of white matter and are also a significant predictor of mortality. Although more than 20% of subjects aged 60 years and older suffer from MPS in Japan, it is often unrecognized and underestimated by patients and medical physicians. We used neuropsychological methods to examine cognitive function and depressive symptoms in subjects with MPS. METHODS: We performed a population-based study in Ama-cho, a rural island town in western Japan. Participants included 951 subjects aged 65 years and older, 613 of whom completed all questionnaires, neurological examinations, and neuropsychological assessments and were included in the data analysis. Subjects were assessed for depression and subjective cognitive impairment using the Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and modified Unified Parkinson's Disease Rating Scale (mUPDRS). RESULTS: Of the 613 participants, 143 were diagnosed with MPS. GDS scores were significantly higher in the MPS group compared with the motor control group, while MMSE scores were significantly lower. CONCLUSIONS: We demonstrated that MPS correlate with both depressive symptoms and cognitive impairment.

Assessment of dementia in patients with multiple system atrophy.

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 (123)I-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.

Epidemiological study of acute encephalitis in Tottori Prefecture, Japan.

BACKGROUND AND PURPOSE: To conduct an epidemiological survey of acute encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in Tottori Prefecture, western area of Japan. METHODS: A questionnaire survey on the annual number of patients aged 16 years or more with acute encephalitis from 2001 to 2005 was undertaken in 2006. RESULTS: During the study period, 49 patients were diagnosed with acute encephalitis. The subtype of acute encephalitis was as follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis associated with collagen disease, one patient with viral encephalitis other than HSE, 20 patients with encephalitis with unknown causes. The service-based incidence rate of acute encephalitis was 19.0 per million person-years. The incidence rate of NHALE subtype was 4.7 per million person-years. CONCLUSIONS: Our epidemiological survey indicated an estimated 550 patients would develop NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.

Executive dysfunction in non-demented Parkinson's disease patients with hallucinations.

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.

Assessment of hallucinations in Parkinson's disease using a novel scale.

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 alpha 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.

Production of dopaminergic neurons for cell therapy in the treatment of Parkinson's disease.

Dopaminergic cell therapy is a potential viable treatment for Parkinson's disease. However, lack of a well-characterized cell preparation of known phenotypic composition containing a high percentage of dopaminergic neurons, has prevented a definitive, controlled, pilot clinical trial from being conducted. We report the successful in vitro expansion of rat E12 mesencephalic progenitors to produce 5-fold the normal number of dopaminergic neurons. The expanded neurons (MAP2+) were detached, resuspended, and formed into small aggregates of 10-200 neurons containing 25-50% of dopaminergic neurons (TH+) that will likely be optimal for use in successful cell therapy. After storage in DPBS, in 0 mM Ca(2+) for up to 24 h at room temperature, aggregated cells were still 90% viable. These results demonstrate that it might be feasible to use a similar protocol to expand human dopaminergic progenitors in vitro. If successful, the requisite large numbers of dopaminergic neurons required to conduct a pilot clinical trial for Parkinson's disease will be produced in vitro. Indications are that the cells can be maintained at optimal viability for the duration of the neural transplantation procedure, under real operating conditions.

[A case of supranuclear hypoglossal nerve palsy with Avellis' syndrome due to a medullary infarction].

We reported a 72-year-old man with left supranuclear hypoglossal nerve palsy and right Avellis' syndrome due to a medullary small infarction. On admission, he showed slight disturbance of consciousness, ocular lateropulsion to the right side, rotatory nystagmus, dysarthria, absent right gag reflex, curtain sign, absent right palatal reflex, deviation of the uvula toward the left side, raise of only the left palate when the patient attempted to utter, paralysis of the right vocal cord and deviation of the tongue toward the left side. Neither atrophy nor fasciculation was observed on the tongue. 124 days after the onset, he had only the left supranuclear hypoglossal nerve palsy and right Avellis' syndrome. MRI showed a small lesion in the medulla, so lateral area of the medulla and a part of the reticular formation medial to the nucleus ambiguous presumed to be involved. These findings suggest that supranuclear pathway to the hypoglossal nucleus of the opposite side exists in the reticular formation near nucleus ambiguous.

[A case of pontine supranuclear facial palsy].

A 56-year-old hypertensive man suddenly developed difficulty in speaking and numbness in the right hand. On admission, he showed moderate right supranuclear facial palsy and right clumsy hand. Three weeks later, he was discharged with only right supranuclear facial palsy. MRI revealed a small infarction in the middle pons. The lesion was situated in the paramedian borderzone between the base and tegmentum. These findings suggest that supranuclear fibers to the facial nucleus descend as a separate bundle from the main pyramidal tract at the mid-pontine level.

[A case of dissecting aneurysm of the basilar artery presented as superior pons type of Foville's syndrome].

Here we report a 47-year-old man with dissecting aneurysm of the basilar artery who developed Foville's syndrome due to upper pons involvement. At first he had an abrupt onset of dysarthria and weakness in his left upper and lower extremities during his work. Neurological examination on admission revealed mild disturbance of consciousness, absent light reaction on the left side, hypesthesia of the left face, absent gag reflex, dysarthria, and left hemiparesis with ataxia. On the second hospital day he developed paralysis of conjugate eye movement to the right, left central facial palsy, and left hemiplegia, and hyperhidrosis of the left side of the body. He was diagnosed to have superior pons type of Foville's syndrome. Computed tomography showed low density area in the right upper pons, and the basilar artery had marked lateral shift, dilatation, and calcification. Vertebral angiography demonstrated dissecting aneurysm of the basilar artery. Although it is very rare that dissecting aneurysm of the basilar artery causes the brain stem symptoms, its possibility should be considered when computed tomography shows marked lateral shift, dilatation, and/or calcification of the basilar artery.

[A case of cerebral pedunclar infarction presenting with pure motor hemiparesis].

Left pure motor hemiparesis occurred in a 42-year-old woman with a history of hypertension and diabetes mellitus. The left hemiparesis affected the arm and leg equally. The face was almost spared, with only a very slight facial asymmetry. Brain CT and MRI showed a small infarction located in the external 2/3 of the right cerebral peduncle. Cerebral angiography did not reveal significant abnormalities.

[The efficacy of X-ray signs for differential diagnosis of small lung cancer and tuberculoma. Committee for Lung Cancer Mass Screening, JATA].

In order to evaluate the efficacy of X-ray signs for the differential diagnosis of small lung cancer from tuberculoma, a cooperative study was carried out. X-ray films of 64 cases (lung cancer 35, tuberculoma 29) were read by 11 experienced chest physicians independently. The positivity of various X-ray signs were assessed respectively and obtained data were analysed with ROC analysis method. "Ill defined contour", "unevenness of density", "paleness" were proved to be relatively useful as a diagnostic tool, but "notch", "pleural indentation" were not useful in differentiating lung cancer from tuberculoma. It was also noted that great interindividual variations existed on the judgements of X-ray signs among chest specialists, and the conquest of which may be a crucial key for the universal validity of these signs.

[Analysis of causative genes and genetic risk factor in Alzheimer's disease].

Recently, some Alzheimer-associated genes have been found: amyloid beta protein precursor (APP), apolipoprotein E (apoE), presenilin 1 (PS-1), and presenilin 2 (PS-2). First, we failed to discover other susceptibility genes of familial Alzheimer's disease (FAD). However, we disClosed a novel mutation. Asp678Asn (D678N), in the APP gene in a pedigree of early-onset Japanese FAD. The alteration in the aggregation properties of mutant A beta may be involved in the pathogenesis of FAD with D678N APP mutation. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheimer's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphism of the ER alpha gene may be a genetic risk factor for SAD.

[Causative genes in Alzheimer's disease].

Recently, some Alzheimer-associated genes have been found: amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand conformation polymorphism and sequence analysis. These seven cases with FAD did not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes of FAD still remain to be not identified. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphisms of the ER alpha gene may be a genetic risk factor for SAD. The apoE genotype is a genetic factor closely related SAD, but it is not full by appreciated how apoE has an effect on developing AD. There are few reports on the quantitative change of apoE, namely the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in the DS as well as AD was significantly higher than that in control group (p < 0.05, p < 0.05, respectively). High levels of apoE mRNA in AD and DS may play an important role in the development of Alzheimer pathology.

Serum proteomic profiling of dementia with Lewy bodies: diagnostic potential of SELDI-TOF MS analysis.

Dementia with Lewy bodies (DLB) is the second most common senile degenerative dementia after Alzheimer's disease (AD). The presentation of overlapping symptoms between these two disorders leads to difficulties in the determination of clinical entities. Serum samples were subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis in order to identify a diagnostic marker for DLB. Four putative protein peaks (m/z 3,883, 4,964, 7,761 and 10,534) were differentially expressed in DLB patients compared to AD patients and control subjects. Receiver operating characteristics (ROC) analysis of a multivariate logistic model of the combination of three peaks (m/z 3,883, 7,761 and 10,534) exhibited the highest discriminatory ability of DLB subjects from non-DLB subjects with a sensitivity of 83.3%, a specificity of 95.8%, a positive predictive value of 90.9% and a negative predictive value of 92.0%. SELDI-TOF MS profiling, therefore, has revealed a serum signature with high diagnostic potential for DLB.

Clinical evaluation of Parkinson's disease dementia: association with aging and visual hallucination.

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.