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Inconsistent results regarding the association between the components of metabolic syndrome and Parkinson's disease (PD) have been reported. We investigated whether the metabolic syndrome or its components, or serum total cholesterol, predict PD incidence in a prospective cohort study design.The study was based on the Mini-Finland Health Survey including 6641 individuals aged 30-79 and free from PD at baseline (1978-1980). During 30 years of follow-up, 89 incident PD cases occurred.After adjustment for sociodemographic and lifestyle factors, the relative risk (RR) of PD was 0.50 (95% confidence interval (CI): 0.30, 0.83) for individuals with the metabolic syndrome compared to those without. This association was especially due to elevated serum triglyceride concentration (≥1.7 vs.1.7 mmol/L, RR = 0.52, 95%CI: 0.30-0.89, P for trend 0.02) and elevated plasma fasting glucose concentration (≥5.6 vs.5.6 mmol/L, RR = 0.56 0.32, 0.98, P for trend 0.05). Elevated serum triglyceride and plasma fasting glucose concentration predicted lower PD risk even after excluding the first 10 years of follow-up. After this exclusion and further adjustment for other components of the metabolic syndrome, a suggestively increased PD risk was observed in overweight individuals (≥25 kg/m(2) vs.25 kg/m(2), RR = 1.75, 95%CI: 1.00, 3.07, P for trend 0.22). Blood pressure, serum HDL cholesterol, or serum total cholesterol carried no prediction of PD risk.Elevated serum triglyceride and plasma fasting glucose concentrations predict low PD incidence whereas high BMI seems to be suggestively related to an increased PD risk.

Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.

The risk factors for Parkinson’s disease (PD) are not well established. We therefore examined the prediction of various lifestyle factors on the incidence of PD in a cohort drawn from the Finnish Mobile Clinic Health Examination Survey, conducted in 1973–1976. The study population comprised 6,715 men and women aged 50–79 years and free of PD at the baseline. All of the subjects completed a baseline health examination (including height and weight measurements) and a questionnaire providing information on leisure-time physical activity, smoking, and alcohol consumption. During a 22–year follow-up, 101 incident cases of PD occurred. The statistical analyses were based on Cox’s model including age, sex, education, community density, occupation, coffee consumption, body mass index (BMI), leisure-time physical activity, smoking and alcohol consumption as independent variables. At first, BMI was not associated with PD risk, but after exclusion of the first 15 years of follow-up, an elevated risk appeared at higher BMI levels (P for trend 0.02). Furthermore, subjects with heavy leisure-time physical activity had a lower PD risk than those with no activity [relative risk (RR) 0.27, 95 % confidence interval (CI) 0.08–0.90]. In variance with findings for other chronic diseases, current smokers had a lower PD risk than those who had never smoked (RR 0.23, 95 % CI 0.08–0.67), and individuals with moderate alcohol intake (at the level of

Sudden memory loss, with prolonged cognitive deterioration, clinically initially resembling a transitory global amnesia (TGA)-like episode, might be caused by ischemic stroke in the hippocampal regions. We report a patient with TGA-type sudden anterograde amnesia and normal head CT. Examinations revealed that the patient had several vascular risk factors and 3 tesla (T) head MRI showed ischemic lesions in diffusion-weighted images (DWI) in both hippocampi. Neuropsychological assessment revealed sustained moderate verbal memory deterioration and abnormal executive functions. We suggest that small ischemic strokes in hippocampal regions might remain unrecognized and underdiagnosed if follow-up of TGA-type episodes is not adequate and if head CT remains the only method of brain imaging.

Background Non-motor symptoms are a major contributor to quality of life in patients with advanced Parkinson's disease (PD). Duodenal levodopa infusion (DLI) has been shown to alleviate motor fluctuations, but data on its possible effect on non-motor symptoms are scarce. The aim of the study was to assess the effect of DLI on blood pressure (BP), sweating, and non-motor symptoms. Methods We evaluated prospectively and open-label nine male patients with advanced PD (age 68.5 ± 6.2 years) treated with DLI because of daily motor fluctuations. Patients were evaluated using orthostatic test, sweating and skin temperature measurements, Unified Parkinson's Disease Rating Scale (UPDRS), Non-motor Symptom Scale (NMSS), and PDQ-39 before and after 2 months of treatment. Results Orthostatic BP drop worsened after 1 week of DLI compared with oral medication (24.1 vs 11.9 mmHg, P = 0.011) and remained significant after 2 months of treatment. UPDRS motor scores improved significantly in 2 months compared with baseline (25 vs 19, P

Background: We present here a case of haemorrhagic brain infarction in a middle-aged and physically active male, who had never smoked. This case report aims to remind the internist and neurologist to bear in mind unusual aetiologies of brain infarcts in patients without classical cardiovascular risk factors. Case Description: A 49-year-old male with pulmonary asthma and a prior history of nasal polyps had a wake-up stroke with left-sided symptoms and speech disturbance. A head MRI and MR angiography revealed a recent haemorrhagic infarct in the right putamen and corona radiata. The left hemiparesis progressed to sensory-motor hemiplegia on the 4th day. In the head CT, it was shown that the haemorrhagic infarct had progressed to a large haematoma. A pansinusitis was also diagnosed. The aetiological investigations revealed a minor atrial septal defect (ASD) with shunting and a heterozygotic clotting factor V R506Q mutation. A remarkable blood eosinophilia of 9.80 E9/l (42%) together with fever, sinusitis, wide-spread bilateral nodular pulmonary infiltrates that did not respond to wide-spectrum antimicrobial treatment, positive anti-neutrophilic cytoplasmic antibodies, a high myeloperoxidase antibody level and slightly positive anti-proteinase 3 antibodies suggested the diagnosis of Churg-Strauss syndrome. These inflammatory symptoms and findings promptly responded to treatment with corticosteroids and cyclophosphamide. Conclusions: Even after the concomitant findings of the low risk factors, i.e. small ASD and heterozygotic clotting factor mutation, continued search for the final aetiology of stroke revealed Churg-Strauss syndrome, which was the key to the treatment.

Background: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. Methods: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968–1972, and analyzed in 2005–2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution9s nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. Results: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97–1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26–3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. Conclusions: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI) showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG). Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease with no effective therapy available. We recorded spontaneous magnetoencephalography and auditory evoked fields (AEFs) from a male patient with a rapidly progressive memory disorder, ataxia and myoclonus. Post-mortem examination confirmed sporadic CJD. Sources of the abnormal slow wave activity were localized with a beamformer software. Sources of sharp transients and AEFs were modeled with equivalent current dipoles. The estimated sources of spontaneous activity abnormalities were more dominant in the left hemisphere, in line with left-dominant abnormalities in diffusion-weighted MRI. Sources of AEFs were found in both temporal lobes. Magnetoencephalography measurements on CJD patients are feasible, and provide efficient means for localizing abnormal cortical activity in CJD.

The inhibition of catechol-O-methyltransferase (COMT) may impair catecholamine clearance resulting in unwanted cardiac and hemodynamic events. We therefore studied the effects of entacapone, an inhibitor of peripheral COMT, on cardiorespiratory and plasma noradrenaline (NA) responses to exercise and on respiratory muscle strength in l-dopa treated patients with Parkinson's disease (PD). A randomized, double-blind, cross-over study with two 1week treatment periods was performed in 15 PD patients. The test battery included analysis of hemodynamics, gas exchange parameters and plasma NA during a maximal exercise test, assessment of maximal static airway pressures and pre- and post-exercise motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The first test was done after withholding l-dopa overnight ('run-in' test, off-phase). The second and third tests were done in on-phase after 1week treatment with either entacapone 200mg or placebo given with each dose of l-dopa. No differences in maximal work load, plasma NA, or in cardiorespiratory responses to either maximal or work rate standardized submaximal exercise were observed between entacapone and placebo, except for O(2) pulse, which was slightly lower (p0.05) after entacapone at submaximal exercise level. Maximal airway pressures were similar between the study treatments and run-in. Exercise had no effect on motor UPDRS after either study treatment or during the run-in test. No serious adverse events were observed. The results of this study suggest that entacapone does not change the work capacity, work efficiency or respiratory muscle strength in l-dopa treated PD patients with mild to moderate disease severity, and that its use with l-dopa seems to be safe in conditions of maximal physical effort. However, data from the long-term use of COMT inhibitors are needed to confirm these findings.

Background Continuous levodopa-carbidopa intestinal gel (LCIG) diminishes daily “off” time and dyskinesia in patients with advanced Parkinson′s disease (PD). Complications are common with percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG-J). Aim of the Study To report the clinical outcome of LCIG in patients with advanced PD in the years 2006–2014 at Helsinki University Hospital. Patients and Methods Levodopa-carbidopa intestinal gel treatment started following PEG-J placement in patients with advanced PD after successful in-hospital LCIG trial with a nasojejunal tube. Demographics, PEG-J procedures, discontinuation of LCIG, complications and mortality were retrospectively analyzed. Results [mean (SD)] Sixty patients with advanced PD [age 68(7) years; duration of PD: 11(4) years] had LCIG treatment for 26(23) months. The majority of patients with advanced PD were satisfied with the LCIG treatment. For 51 patients (85%), the pump was on for 16 hr a day, and for nine patients (15%) it was on for 24 hr a day. After 6 months, the levodopa-equivalent daily dose (LEDD) had increased by 30% compared to pre-LCIG LEDD. Sixty patients underwent a total of 156 PEG-J procedures, and 48 patients (80%) had a total of 143 complications. Forty-six patients (77%) had 119 PEG-J or peristomal complications, and 22 patients (37%) had a total of 25 other complications. The most common complications were accidental removal of the J-tube in 23 patients (38%) and ≥5% weight loss in 18 patients (30%). Fifteen patients discontinued the LCIG after 21 (21) months. At the end of the follow-up period of 33(27) months, 38 patients were still on LCIG and nine (15%) had died. Conclusion Most patients were satisfied with LCIG treatment. A few patients lost weight whereas the majority had complications with PEG-J. When LCIG treatment is carried out, neurological and endoscopic units must be prepared for multiple endoscopic procedures.

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel α-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.

Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Both are used, often simultaneously, as adjuncts to L-dopa/dopa decarboxylase (DDC) inhibitor treatment of Parkinson's disease (PD). Their possible interactions have not been previously studied in a double-blind manner.We studied clinical response, tolerability, haemodynamics and cardiac rhythm in 16 PD patients with end-of-dose-type motor fluctuations. The patients' individual L-dopa/DDC inhibitor treatment was stabilized before the experimental treatments. This was followed by three consecutive, randomized, double-blind 2-week treatment periods with entacapone (200mg with each L-dopa dose), selegiline (10mg o.d.) or both entacapone and selegiline with the L-dopa/DDC inhibitor medication. Clinical efficacy (L-dopa test with repeated motor and dyskinesia scoring) and safety (orthostatic test, 24-h ambulatory ECG, haematological and clinical chemistry variables and adverse events) evaluations were performed before each treatment (control) and at the end of each treatment period.All three treatments, entacapone, selegiline, and entacapone+selegiline as adjunct to L-dopa/DDC inhibitor improved (p0.05) clinical disability compared to L-dopa only but they did not differ significantly from each other. Dyskinesias increased with all the treatments, statistically significantly (p0.01) with entacapone+selegiline. No significant differences in haemodynamics were observed between control and any of the experimental treatments, or between the experimental treatments in the orthostatic test. One patient already had symptomatic orthostatism before experimental treatments (control). In two other patients orthostatism emerged after the introduction of selegiline, and in one after every experimental treatment. Twenty-four-hour ECG did not show any differences in supraventricular or ventricular extrasystoles or heart rate between treatments. No statistically significant differences were observed in adverse events or in haematology and clinical chemistry variables. One patient treated with entacapone+selegiline discontinued the study due to dizziness and insomnia. Our results suggest that co-administration of entacapone with L-dopa/DDC inhibitor, with or without selegiline, improves clinical disability, is safe, but may also enhance dopamine-related adverse events to some extent in PD patients with end-of-dose type motor fluctuations.

The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by35% (p0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together with L-Dopa and selegiline in patients with PD, although further studies with larger number of patients and longer treatment periods are necessary to confirm this finding.

Evidence suggests possible Parkinson's disease (PD)–relevant neural effects of exposure to polychlorinated biphenyls. Limited epidemiological evidence suggests that polychlorinated biphenyl exposure may increase PD risk, but no studies have involved biomarkers of polychlorinated biphenyl exposure before PD onset. We examined the prospective association between serum polychlorinated biphenyls and PD. We conducted a nested case–control study within the Finnish Mobile Clinic Health Examination Survey with serum samples collected during 1968–1972 and analyzed in 2005–2007 for polychlorinated biphenyls. Incident PD cases were identified through the Social Insurance Institution's registry and were confirmed by medical record review (n = 101). Controls (n = 349) were matched on age, sex, municipality, and vital status. We used logistic regression to estimate adjusted odds ratios. There was no evidence of increasing risk of PD with increasing polychlorinated biphenyl exposure in adjusted analyses. Instead, there was a trend toward lower odds of PD with increasing serum polychlorinated biphenyl concentrations, which was most pronounced for the sum of all measured polychlorinated biphenyl congeners and the sum of dioxin-like congeners. Compared with that of those in the lowest quintile, the odds ratio of PD among those in the highest quintile of total polychlorinated biphenyls was 0.29 (95% confidence interval, 0.12–0.70; P trend = .02) and for dioxin-like congeners was 0.34 (95% confidence interval, 0.13–0.90; P trend = .05). These results do not support an increased risk of PD from polychlorinated biphenyl exposure and instead suggest a possible protective effect of polychlorinated biphenyl exposure. © 2012 Movement Disorder Society

Creutzfeldt-Jakob Disease (CJD) is a rare neurodegenerative disease, which belongs to a group of spongiform encephalopathies termed prion diseases.

We have compared the effects of entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic responses in L-Dopa/dopa decarboxylase inhibitor-treated patients with Parkinson's disease (PD). In a double-blind, randomized, crossover study with two consecutive 1-week treatment periods, a battery of cardiovascular reflex tests (orthostatic, Valsalva, deep breathing, and isometric hand grip tests) was performed in a group of 15 patients with idiopathic PD. The first set of tests was performed after withholding L-Dopa overnight (control, "off" stage). The second and third sets of tests were performed in "on" stage after 1-week treatment with either entacapone 200 mg or placebo administered with each dose of L-Dopa/dopa decarboxylase (DDC) inhibitor. Valsalva, deep breathing, and orthostatic tests demonstrated no statistically significant differences in the ratio of the longest and shortest electrocardiographic R-to-R wave (R-R) intervals between entacapone and placebo or between study treatments and control. Blood pressure responses to both orthostatic challenge and prolonged isometric work (hand grip test) were similar between treatments. Systolic orthostatic hypotension was observed in only one patient during the control test, but it occurred more frequently after L-Dopa/DDC inhibitor, regardless of concomitant administration of either entacapone (n = 3) or placebo (n = 4). Peripheral COMT inhibition with entacapone does not significantly alter cardiovascular autonomic responses in L-Dopa-treated patients with PD.

To compare plasma levodopa concentrations after repeated doses of levodopa/carbidopa/entacapone (LCE) and levodopa/carbidopa (LC). Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson’s disease patients) received levodopa 100 mg or 150 mg four times daily, respectively, and groups III and IV (healthy volunteers) received the same strengths of levodopa five times daily. Pharmacokinetic (PK) parameters determined for levodopa included Cmin, Cmax, Cmax − Cmin, AUC, t1/2, and tmax. In healthy volunteers and PD patients, mean trough levels (Cmin), Cmax, and AUC of levodopa were, in general, significantly higher during LCE compared to LC administration. Compared to Cmin, Cmax, and AUC, differences between the treatments in variability of levodopa concentrations (Cmax − Cmin) were less consistent. The present results on the differences in levodopa PK between LCE and LC provide a basis to evaluate the relationship of levodopa PK and the induction of motor complications in an on-going study in early Parkinson’s disease using similar dosing regimens.