Olfactory dysfunction is related to postoperative delirium in Parkinson's disease.

Operations often lead to delirium in elderly patients, particularly those with impaired cognition, suggesting that underlying neuropathology may play a role in the development of postoperative delirium. Olfactory dysfunction is a well-known marker of underlying Lewy body pathology in Parkinson's disease (PD). However, the prognostic value of olfaction for the development of postoperative delirium in PD remains unclear. 34 PD patients with or without postoperative delirium following surgery under general anesthesia were included in this study (n = 17 for each group). Cross-Cultural Smell Identification scores were lower in PD patients with postoperative delirium (4.4 ± 1.5) relative to the delirium-free controls (6.8 ± 2.4, p < 0.005). Multivariate logistic regression analysis revealed that olfaction and operation time were significant predictors of the development of postoperative delirium. Impaired olfaction is significantly associated with postoperative delirium in PD. Olfaction may be useful for identifying PD patients susceptible to postoperative delirium.

Vitamin D deficiency and its relationship with endothelial dysfunction in patients with early Parkinson's disease.

Increasing evidence has shown that individuals with Parkinson's disease (PD) have lower levels of 25-hydroxyvitamin D (25[OH]D) than healthy controls. Low vitamin D has been associated with endothelial dysfunction which may play a role in the pathogenesis and progression of PD. Flow-mediated dilation (FMD) is widely used as a clinical marker of overall endothelial function. We evaluated the relationship between serum 25(OH)D levels and FMD in PD. We enrolled 81 patients with early PD and 52 healthy controls, and we evaluate endothelial function based on vitamin D status and identify the association between FMD and vitamin D status in patients with early PD. The mean serum 25(OH)D levels were significantly lower in the PD patients than in the controls (21.8 ± 9.5 vs. 25.2 ± 9.3 ng/mL, p < 0.05). FMD was significantly lower in the PD patients (7.1 ± 1.8 %) than in the controls (8.1 ± 2.1 %, p < 0.05). The serum 25(OH)D was significantly associated with FMD independently of age, cardiovascular disease risk factors, body mass index, motor Unified PD Rating Scale status and homocysteine levels (adjusted R (2) = 0.331, ß = 0.494, p < 0.001). These findings provide evidence of a possible association between endothelial dysfunction as assessed by FMD and low vitamin D status in patients with early PD.

Endothelial dysfunction and hyperhomocysteinemia in Parkinson's disease: flow-mediated dilation study.

BACKGROUND: Levodopa (l-dopa) therapy in Parkinson's disease (PD) increases serum homocysteine levels because of its metabolism via catechol O-methyltransferase, which may lead to endothelial dysfunction. METHOD: We enrolled 40 PD patients treated with l-dopa, 33 PD patients treated with l-dopa/entacapone, 22 untreated PD and 30 controls, and compared the flow-mediated dilation in these subjects. RESULTS: The flow-mediated dilation was significantly lower in PD patients with l-dopa (6.0 ± 1.8%) than in those with l-dopa/entacapone (7.2 ± 1.1%, P = 0.03), untreated PD patients (7.8 ± 1.2%, P < 0.05), and controls (8.5 ± 2.9%, P < 0.05). The homocysteine level was significantly higher in PD patients with l-dopa than in other groups. In a multivariate logistic regression model, the uppermost homocysteine quartile was an independent predictor of the lowest tertile of flow-mediated dilation (odds ratio, 6.33; 95% confidence interval, 1.61-26.65; P = 0.012). CONCLUSIONS: Our findings indicate that endothelial dysfunction may be associated with chronic l-dopa treatment in patients with PD.

The mild cognitive impairment stage of dementia with Lewy bodies and Parkinson disease: a comparison of cognitive profiles.

BACKGROUND: Recent studies have demonstrated that structural and pathologic changes are more severe in patients with dementia with Lewy bodies (DLB) than in those with Parkinson disease with dementia (PDD). We investigated neuropsychological characteristics of patients with mild cognitive impairment (MCI) stage of DLB (DLB-MCI) and PD (PD-MCI) based on the hypothesis that the pathologic differences between DLB and PDD can influence cognitive profiles in the MCI stage of these diseases. METHODS: Baseline demographic characteristics and neuropsychological data obtained from patients with DLB-MCI (n=20) and PD-MCI (n=46) were compared. RESULTS: The patients with DLB-MCI showed poorer cognitive performance in the Stroop, Go-No-Go, and semantic fluency tests compared with those with PD-MCI. In addition, patients with DLB-MCI had lower scores on visual and verbal memory performance and in the visuospatial domain compared with PD-MCI patients. CONCLUSIONS: Our results demonstrate that patients with DLB-MCI have more severe cognitive impairment in frontal executive, memory, and visuospatial functions than those with PD-MCI. These data suggest that differences in pathologic substrates between PDD and DLB may begin in the MCI stage of the 2 diseases and may lead to differences in cognitive profiles.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). RESULTS: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. CONCLUSIONS: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

Posterior circulation embolism as a potential mechanism for migraine with aura.

BACKGROUND: Although the mechanism of migraine is regarded as a functional disorder of the brain, numerous studies have reported that migraine is closely associated with vascular system abnormalities. CASE REPORTS: We describe a 19-year-old female with recurrent migraine attacks and typical aura for 7 years. MRI showed multiple stroke lesions in the posterior circulation. Moreover, a pseudoaneurysm (1.9 × 1.4 cm) originating from the left vertebral artery was observed on four-vessel angiography. Multiple microembolic signals (MES) were repeatedly observed in the basilar artery using 30-minute transcranial Doppler monitoring. Interestingly, MES and her typical migrainous symptoms disappeared simultaneously with removal of the pseudoaneurysm. DISCUSSION: This case supports the fact that microemboli play a pivotal role in the development of migraine attacks.

Hemodynamic impact of fetal-variant Willisian circle on cerebral circulation: a duplex ultrasonography study.

BACKGROUND/AIMS: The Willisian circle can redistribute the vertebrobasilar flow and the reduction of flow is attributable to orthrostatic presyncope. To evaluate this hemodynamic aspect, we investigated anterior and posterior cerebral blood flow (CBF) volume distributions according to the variation of the Willisian circle, and compared those between controls and patients with presyncope. METHODS: Subjects underwent cerebral CT angiography and color-coded duplex sonography measuring flow volumes of the internal carotid artery (ICAs) and vertebral artery (VAs). According to clinical manifestations and Willisian configurations, CBF volume patterns were analyzed. RESULTS: Between the presyncope (n = 25) and control groups (n = 76), the prevalence of fetal-variant Willisian configuration (48% vs. 21%, p = 0.004) and posterior CBF volume (126 ± 85 vs. 165 ± 64 ml/min, p = 0.015) was significantly different, but A1 morphology, anterior CBF, and total CBF volumes were not. Total CBF volume was 769 ± 176 ml/min (80% ICAs and 20% VAs). The posterior CBF volume lowered significantly (172 ± 70 vs. 122 ± 62 vs. 92 ± 44 ml/min; p < 0.001) toward the two-sided fetal type variation, although total CBF volume is similar among the three groups (p = 0.742). CONCLUSIONS: The present study suggests that Willisian configuration contributes to orthostatic presyncope and flow distribution of the cerebral circulation.

A case-control study of multiple system atrophy in Korean patients.

A few case-control studies of multiple system atrophy (MSA) have been reported in Western populations. In this study, we included various epidemiological factors to evaluate whether the risk factors for MSA differed in Korean and Western populations. A total of 100 consecutive MSA patients and 104 controls at two referral hospitals participated. Information was obtained through face-to-face interviews using a structured questionnaire: history of living area, occupational history, food habits, alcohol and tobacco consumption, and use of drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using logistic regression. The multivariate logistic regression analysis revealed that use of antihypertensive medication (OR = 0.30 [0.12-0.78]) and vitamins (OR = 0.30 [0.14-0.64]) and consumption of meat and poultry (OR = 0.27 [0.13-0.56]) were associated with decreasing risk for MSA, whereas use of herbal medications (OR = 3.17 [1.28-7.84]) was associated with increasing risk for MSA. In univariate analysis adjusted for age, sex, education level, and recruitment center, use of aspirin (OR = 0.21 [0.07-0.61]) and coffee consumption (OR = 0.44 [0.23-0.84]) were significantly less frequent in MSA patients than in controls, whereas heavy smoking (≥40 pack-years) was significantly more prevalent in MSA patients than in controls (OR = 3.44 [1.05-11.23]). There was no difference in living area, participation in farming, or exposure to agrichemicals and solvents between groups. This study showed that MSA in Korea is characterized by risk factors that are both similar to and different from those affecting Western populations and that herbal medicines constitute a new MSA risk factor for the Korean population.

Is an Isolated Weight-Holding Tremor a New Subtype of Isometric Tremor?

A weight-holding tremor is a rare type of hand tremor that occurs only when someone holds some weight. Here we report three cases of isolated weight-holding tremors, of which one patient was diagnosed with Parkinson's disease (PD) and the others as a variant of essential tremor (ET). A 68-year-old woman presented with a left-hand tremor that appeared only when she held objects with some weight. Her tremor was reminiscent of the re-emergent tremor of PD, and dopamine transporter imaging revealed reduced uptake at the right posterior putamen. A 21-year-old man and a 71-year-old woman also presented with similar weight-holding tremors. However, these tremors were not re-emergent, and no signs of parkinsonism were observed during follow-up. Although the underlying etiologies of these tremors differed, all three tremors worsened as the held weight increased. These tremors could be isolated isometric tremors, but further research is needed to clarify the nature of this rare tremor.

Serum cholesterol levels and the risk of multiple system atrophy: a case-control study.

Cholesterol in brain membranes may modulate the conformational state and accumulation of alpha-synuclein in alpha-synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the alpha-synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age- and gender-matched healthy people with no neurological disease. The levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL-C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL-C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol-lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3-11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2-5.5, P = 0.016) for those in the lowest quartile of HDL-C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA.

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.

Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset

Changes in cerebral glucose metabolism in patients with Parkinson disease with dementia after cholinesterase inhibitor therapy.

UNLABELLED: We investigated changes in cerebral glucose metabolism after cholinesterase inhibitor (ChEI) therapy in patients with Parkinson disease dementia (PDD) to determine whether cognitive improvements would be reflected in changes of cerebral metabolic patterns, thus offering insight into the neural substrate of cognitive dysfunction in patients with PDD. METHODS: We performed a serial PET study before (baseline) and after ChEI therapy on 10 patients with PDD, using statistical parametric mapping. Additionally, covariance analysis was performed to extract regions in which increased change in regional cerebral metabolism correlated significantly with increased Mini-Mental State Examination scores. RESULTS: The statistical parametric mapping analysis indicated that significantly increased cerebral metabolism after ChEI therapy, compared with at baseline, was most evident in the left angular gyrus extending to the supramarginal area and left superior and middle frontal gyri. Additionally, cerebral metabolism was significantly increased in the right superior frontal and left middle orbitofrontal gyri. In contrast, the right fusiform gyrus showed significantly decreased metabolism after ChEI, compared with at baseline. In the correlation analysis, improvements in Mini-Mental State Examination scores after ChEI treatment were significantly associated with increased cerebral metabolism in the left supramarginal, orbitofrontal, and cingulate areas. CONCLUSION: Our data suggest that prefrontal and parietal association areas may be relevant structures for the pharmacologic response to ChEI in patients with PDD.

Movement disorders at a university hospital emergency room. An analysis of clinical pattern and etiology.

We prospectively evaluated the clinical features and etiologies of all common categories of movement disorder seen in the emergency room (ER) of an urban university hospital over a period of 12 months. We divided movement disorders according to the presenting phenomenology likely to dominate the clinical presentation, that is, gait disorder, tremor, dystonia, myoclonus, and acute akinetic crisis and classified a specific etiology in the individual phenomenology. In one year, there were 60,002 ER visits; of these, 58 (0.09 %) were diagnosed as a primary movement disorder. The most common clinical presentation was gait disorder (n = 21, 36.2 %), followed by myoclonus (n = 16, 27.6 %), dystonia (n = 10, 17.2 %), tremor (n = 8, 13.8 %), and acute akinetic crisis (n = 3, 5.2 %). Comparing the movement disorders, the mean age of the patients with dystonia was significantly lower than that of patients with other movement disorders (P < 0.001). Of the patients, 37 (63.8 %) had drug-related movement disorders. The contribution of drugs was significantly higher in patients with dystonia compared with the other movement disorders (P < 0.01). Our study showed that a large proportion of the movement disorders seen in the ER are drug-related. Careful selection of drugs while prescribing would decrease movement disorder-related visits to the ER.

Odour identification test and its relation to cardiac 123I-metaiodobenzylguanidine in patients with drug induced parkinsonism.

We investigated olfactory function and its relation to cardiac 123I-metaiodobenzylguanidine (MIBG) uptake in 15 patients with drug induced parkinsonism (DIP). The mean Cross Cultural Smell Identification (CCSI) score was significantly greater in patients with DIP than in those with Parkinson's disease (PD: 6.9 (1.6) vs 4.4 (2.2); p<0.001); however, the mean CCSI score in patients with DIP was not significantly different from controls. One patient with DIP, whose CCSI score was significantly reduced, also exhibited decreased cardiac MIBG uptake. DIP patients with CCSI scores within the normal range had normal cardiac MIBG uptake. Our study suggests that an olfactory function test may be a useful tool for detecting DIP unrelated to PD and for identifying patients with DIP who have subclinical PD.

Internal and cortical border-zone infarction: clinical and diffusion-weighted imaging features.

BACKGROUND AND PURPOSE: The pathogenesis of internal border-zone (IBZ) and cortical border-zone (CBZ) infarcts is unclear. Both types of infarct have been combined into a single group in most previous reports, which has produced conflicting results. We hypothesized that different pathogenic mechanisms underlie IBZ and CBZ infarcts. METHODS: We reviewed 946 consecutive patients with ischemic stroke within the middle cerebral artery territory. IBZ and CBZ infarcts were selected based on diffusion-weighted imaging templates to identify vascular territories. Baseline patient characteristics, clinical courses, and neuroradiological features were compared between patients with IBZ and CBZ infarcts. RESULTS: We identified 45 IBZ and 75 CBZ infarct patients. Compared with the CBZ infarct patients, IBZ infarct patients had a higher degree of stenosis or occlusion in either the middle cerebral or internal carotid artery (P=0.008) and exhibited a rosary-like pattern of infarction more frequently (P<0.001). In contrast, concomitant small cortical infarcts were observed more frequently in CBZ infarct patients (P<0.001). Clinical deterioration during the first 7 days of admission and poor outcome after 3 months after stroke was more prevalent in IBZ infarct patients than in CBZ infarct patients (P=0.002 and P=0.003, respectively). CONCLUSIONS: IBZ infarcts are caused mainly by hemodynamic compromise, whereas embolic pathogenesis appears to contribute greatly to the genesis of CBZ infarcts. Patients with IBZ infarcts showed poor early and late clinical courses. Our findings suggest that different therapeutic approaches may be required to prevent early clinical deterioration in patients with different types of border-zone infarcts.

Comparison of spontaneous intracranial vertebral artery dissection with large artery disease.

OBJECTIVE: To compare clinical and angiographic characteristics and stroke patterns between spontaneous intracranial vertebral artery dissection (VAD) and vertebral large artery disease (LAD) (atherosclerosis). DESIGN: Retrospective study. SETTING: Tertiary referral center for cerebrovascular diseases. Patients Twenty-two patients with spontaneous VAD and 25 with LAD in the intracranial portion of the vertebral artery. MAIN OUTCOME MEASURES: We compared (1) clinical characteristics, including epidemiologic data, vascular risk factors including inflammatory markers, the presence of headache, and stroke syndromes and severity; (2) stroke pattern on diffusion-weighted imaging, which was classified as vertebral perforator infarct, basilar perforator infarct, small scattered infarct, large scattered infarct, and territorial infarct; and (3) angiographic findings, ie, the distribution of involved arteries, degree of stenosis, and the involvement on the anterior circulation and calcification of vertebral artery. RESULTS: Although patients with VAD were younger, and more often had headaches and fewer vascular risk factors than those with LAD (P<.01 in all cases), these clinical features were also observed in some LAD patients. Diffusion-weighted imaging data showed that vertebral perforator infarct and small scattered infarct were most common in the VAD group, while territorial infarct and large scattered infarct were most common in the LAD group (P = .02). On angiography, LAD more frequently had anterior circulation arterial involvement (P = .002), higher degree of stenosis (P = .002), and calcifications (P = .008). CONCLUSION: Our findings indicate that results of diffusion-weighted imaging and noninvasive vascular studies might provide clues to the clinical characteristics in differential diagnosis between VAD and LAD.

Two cases of spontaneous middle cerebral arterial dissection causing ischemic stroke.

Spontaneous middle cerebral arterial dissection (MCAD) is a rare cause of ischemic stroke. We report two cases of isolated spontaneous MCAD causing ischemic stroke. MCAD should be considered when a young patient has a middle cerebral artery territory infarct with stenosis at the origin of the middle cerebral artery. We discuss noninvasive radiological techniques for the diagnosis of MCAD.

Repetitive involuntary leg movements in patients with brainstem lesions involving the pontine tegmentum: evidence for a pontine inhibitory region in humans.

Repetitive involuntary limbs movements have been mostly reported in patients with extensive brainstem pathologies, but the region responsible is unknown. We describe two patients with progressive basilar artery infarcts who showed automatic stepping and one patient with an osmotic demyelination disorder who showed periodic involuntary leg movements. By subtracting diffusion-weighted images before and after the development of repetitive involuntary leg movements, the brainstem lesion responsible for the involuntary movements was distinctively located in the vicinity of the pontine tegmentum, which is known as the pontine inhibitory region in animal studies.