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In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

The diagnosis of cognitive impairment and dementia often occurring with Parkinson's disease (PD) is still based on the clinical picture and neuropsychological examination. Ancillary methods to detect cognitive decline in these patients are, therefore, needed. Alterations in the latencies and amplitudes of evoked response potential (ERP) components N100 and P200 have been described in PD. Due to limited number of studies their relation to cognitive deficits in PD remains obscure. The present study was designed to examine if alterations in the N100- and P200-potentials associate with neuropsychological impairment in PD. EEG-ERP was conducted to 18 PD patients and 24 healthy controls. The patients underwent a thorough neuropsychological evaluation. The controls were screened for cognitive impairment with Consortium to Establish Alzheimer's disease (CERAD)-testing and a normal result were required to be included in the study. The N100-latency was prolonged in the patients compared to the controls (p = 0.05). In the patients, the N100 latency correlated significantly with a visual working memory task (p = 0.01). Also N100 latency was prolonged and N100 amplitude habituation diminished in the patients achieving poorly in this task. We conclude that prolonged N100-latency and diminished amplitude habituation associate with visual working memory impairment in PD.

Cognitive changes are common in Parkinson's disease (PD). Low plasma uric acid (UA) level is associated with risk of PD and predicts faster progression of motor symptoms in established disease. Whether UA levels predict cognitive changes has not been studied. In a crossectional study, our group has previously shown an association of plasma and urine UA levels with cognition in PD. The aim of the present controlled longitudinal study was to examine the evolution of cognitive changes and the prognostic value of the UA levels on cognition in the previously reported PD-patient cohort. Of the original 40 patients, 31 were available for follow-up after three years. Both plasma and daily urine UA levels were measured, nutrition was evaluated using 4-day dietary recall diary and cognition was assessed by a thorough neuropsychological examination including computerized tasks with Cognispeed©. The plasma and urine UA levels of the patients remained stable during the follow-up. At the same time, the rate of cognitive decline was unexpectedly slow. A statistically significant deterioration was noted in verbal fluency (p=0.04) and in Cognispeed©'s vigilance task (p=0.0001). In forward linear regression analysis only the baseline daily urine UA level contributed to verbal fluency (p=0.01), picture completion (p=0.001), block design (p=0.006), vigilance (p=0.006), subtraction (p=0.01) and statement verification (p=0.04) tasks. The implications of the study results are discussed.

Background: The role of admission blood glucose level on the prognosis of patients with intracerebral haemorrhage has not been elucidated. Objective: To examine this association on the basis of an epidemiologically representative patient material. Methods: 249 500 people living in the catchment area of the Central Hospital of Central Finland. The diagnosis of ICH was established if verified by cranial computed tomography (CT) or autopsy. Results: Of the 416 patients who fulfilled the diagnostic criteria, 30 died before admission and 386 were admitted to the Central Hospital. All 329 patients (290 nondiabetics and 39 diabetics) with both admission blood glucose and cranial CT data were included in the study. The mean blood glucose level was 10.6 mmol/l for nondiabetics who died on the day of onset, 8.6 mmol/l for those dying during days 1 to 28, and 6.8 mmol/l for the 28 day survivors. The corresponding figures for diabetics were 13.9 mmol/l, 12.5 mmol/l, and 9.3 mmol/l. In both nondiabetics and diabetics, patients who died had significantly higher mean glucose than the 28 day survivors (p

Placebo-controlled clinical trials with nimodipine in acute ischemic stroke have not fulfilled the early optimistic expectations. Nimodipine has in some experimental studies, when administered either before or up to 90 min after induction of cerebral ischemia, resulted in a reduction of infarct size. No studies on the effects of nimodipine on infarct size in man have been published. We measured the infarct volumes in the admission and control CT examinations 3 weeks to 3 months later in 153 patients who had participated in a multicenter, randomized and placebo-controlled study. No statistically significant differences overall were found within or between the treatment groups. Subgroup analyses revealed in the placebo, but not in the nimodipine arm, an increase in the median infarct volumes if the treatment was started within 24 h of onset, and if the volume in the admission CT was less than median. A beneficial effect of nimodipine in prevention of infarct size increase in these circumstances cannot be excluded.

Cognitive dysfunction is common in Parkinson's disease (PD). Low plasma uric acid level is a risk factor for PD but its association with cognitive impairment in PD has not been previously studied. In the present study urine uric acid level as well as plasma uric acid- and homocysteine levels were measured in 40 patients with PD. Comprehensive neuropsychological tests including computerized tasks were performed on all. Both low plasma and low urine uric acid levels associated with decreased neuropsychological performance. In multiple linear regression low urine uric acid level predicted worse performance in the Picture completion subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p=0.003) and in the Rule shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (p=0.04). Low plasma uric acid level predicted worse performance both in the Picture completion (p=0.02) and Similarities subtest of the WAIS-R (p=0.02). Reaction time and the time spent on cognitive processing in the Statement verification task were inversely correlated with the uric acid levels (p=0.0001). There was no correlation between the homocysteine level and neuropsychological performance. Instead, the plasma uric acid and homocysteine levels correlated significantly and their possible association in PD is discussed.

Objectives: To determine the long term survival and predictors of death in patients with primary intracerebral haemorrhage (ICH) in Central Finland. Methods: Data were collected retrospectively on all adult patients with first ever ICH in Central Finland county between September 1985 and December 1991. The survival of all patients at the end of December 2002 was investigated. Kaplan–Meier survival curves were constructed and factors associated with both early (⩽28 days) and late deaths determined. Long term survival was compared with the general Finnish population of the same age and sex distribution. The causes of death were compared with those of the population of Central Finland. Results: 411 patients with first ever ICH were identified, 199 men (mean age 64.9 years) and 212 women (mean age 69.5); 30 died before hospital admission, and 208 (50.6%) within the first 28 days. In Kaplan–Meier analysis, at 16 years the cumulative survival was 3.2% for men and 9.8% for women. The 28 day survivors had a 4.5-fold increased annual risk of dying during the first year after ICH, and 2.2-fold during years 2 to 6. On admission, significant independent predictors of death within the first four weeks were unconsciousness, lateral shift of cerebral midline structures, mean arterial pressure ⩾134 mm Hg, hyperglycaemia, anticoagulant treatment, and ventricular extrasystoles. Predictors of late death for the 28 day survivors were old age, male sex, and heart failure. Conclusions: Primary intracerebral haemorrhage has a poor short and long term outcome. The results emphasise the importance of primary and secondary prevention for ICH.

Background and Purpose Clinical trials of new drugs that reverse neurological deficits when used in the first hours of stroke onset suggest that early hospital admission is important. We analyzed a database of patients with acute stroke to determine the factors that delay hospital admission. Methods We analyzed all patients with their first stroke during 1993 in the province of Central Finland (population, 256 000). Patients referred to the Central Hospital, the only tertiary referral hospital in the area, were included in the study. Results Of the patients with first stroke, 363 (79%) were admitted to the Central Hospital. The stroke subtype was confirmed in 356 (98%) patients with CT scan, and the patient population included 272 (75%) with brain infarction, 51 (14%) with intracerebral hemorrhage, and 40 (11%) with subarachnoid hemorrhage. The most important factor associated with a delay in reaching the hospital was the referral pattern. The median delay was 2 hours for patients brought directly to the Central Hospital, 8 hours if a physician at the local health center was consulted, and 47 hours if the patient was first admitted to the health center for observation. Other factors associated with a delay were ischemic stroke and stroke onset in the evening or night or during the weekend. Conclusions The majority of patients who are candidates for acute stroke trials arrive at the hospital after prolonged delays for multiple reasons. Public and medical personnel education could result in significant reduction in these delays.

The predictive value of serum cortisol level on the prognosis in acute brain infarction of the carotid circulation territory was studied in 101 patients younger than 70 years. The levels of 7 a.m. and 7 p.m. serum cortisol were measured initially and at 1 week. All patients underwent a computed cerebral tomography (CT) within 2 days of the onset of symptoms, and a second CT 3 weeks or 3 month later. Serum cortisol values predicted the stroke outcome. Both the 7 a.m. and the 7 p.m. values in the initial and 1-week samples correlated positively with the severity of hemiparesis on the corresponding days. The 7 p.m. values predicted better than the 7 a.m. values the functional outcome and case fatality during the 3 month follow-up. Initially and at 1 week, the median 7 p.m. serum cortisol values were statistically significantly higher in those with frontally extending infarcts than in those with non-frontal infarcts. Both 7 a.m. fasting blood glucose and glycosylated hemoglobin (HbA1c) measurements were taken within 3 days of the onset in 95 cases. The patients were diagnosed to have prestroke normoglycemia (n = 73) and hyperglycemia (n = 22) on the basis of the HbA1c level. A highly significant (P = 0.0001) correlation was demonstrated between the initial 7 p.m. cortisol and 7 a.m. fasting blood glucose values in those with prestroke normoglycemia, suggesting that hyperglycemia during the acute phase of stroke is a stress response.

We read with great interest the article by Uyttenboogaart and co-workers on the association of serum glucose level with outcome in acute ischaemic stroke. In their multivariate analysis hyperglycaemia (glucose >8 mmol/l) was associated with worse functional outcome in a concentration-dependent manner in non-lacunar stroke, whereas in lacunar stroke hyperglycaemia was associated with favourable outcome, this beneficial effect diminishing with more severe hyperglycaemia (>12 mmol/l). Although Uyttenboogart and colleagues creditably discuss the potential neuroprotective effect of lactate produced by astrocytes, they fail in their conclusions stating that ‘hyperglycaemia has a detrimental effect in non-lacunar stroke, but moderate hyperglycaemia …

Progressive myoclonus epilepsy without Lafora's bodies (PME) is a rare inherited disease found predominantly in Finland, where the incidence is one case per 20,000 to 30,000 children. This fatal disease is characterized by normal early development, progressive stimulus-sensitive myoclonus, ataxia, dysarthria, occasional grand mal seizures, and loss of cerebellar Purkinje cells. Concentrations of gamma-aminobutyric acid in the CSF averaged 89 +/- 10 pmole/mL (mean +/- SE) in eight patients with PME, compared with 135 +/- 18 pmole/mL in ten control patients. The concentrations of adenosine (16 pmole/mL v 17 pmole/mL), inosine (560 pmole/mL v 570 pmole/mL) and hypoxanthine (6.2 nmole/mL v 6.1 nmole/mL) were the same in patients with PME and in controls.

Smoking habits were analysed in 114 patients with subarachnoid haemorrhage, less than 70 years old, obtained from an epidemiological study. One control, matched for age, sex, and domicile, was selected for each patient. Current cigarette smokers were significantly more prevalent among cases than controls, and the relative risk of subarachnoid haemorrhage compared with non-smokers was 2.7 in men and 3.0 in women. The so called metastatic emphysema theory with increased elastolytic activity in the serum of smokers is proposed as biochemical basis for the increased risk of subarachnoid haemorrhage.

Summary: Seventy-five epilepsy patients with at least two complex partial seizures/month were treated with γ-vinyl GABA (GVG) 3 g/day for 3 months. Forty-one patients (54%) showed a reduction of 50% in seizures. The median monthly seizure frequency decreased from 11.5 to 4 seizures/month. Twenty percent of patients had an improvement in general performance without a significant reduction in seizures. The responders entered the second phase of the study, in which 28 patients were randomly allocated to 3 g/day and 25 patients to 1.5 g/day GVG under double-blind conditions. The dosage of 3 g/day appeared to be clearly more effective than 1.5 g/day. However, even with 1.5 g/day GVG the seizure frequency was significantly reduced as compared to baseline. Drowsiness was the most commonly observed side effect, and it diminished with continued treatment. In three cases side effects led to the withdrawal of GVG therapy. RESUME 75 patients epileptiques presentant un minimum de 2 crises partielles complexes par mois ont ete traites pendant 3 mois par le gamma-vinyl-GABA (GVG) a la dose de 3 g/j. 41 patients ont presente une reduction superieure ou egale a 50% de la frequence des crises. La frequence mensuelle mediane est passee de 11.5 a 4.20% des patients ont beneficie 'une amelioration generale des performances sans diminution significative du nombre des crises. Les patients qui avaient repondu au traitement ont participea la seconde partie de 'etude, effectuee en double aveugle: 28 patients tries au sort ont reu 3 g/j de GVG tandis que 25 patients ne recevaient plus que 1.5 g/j de GVG. La dose de 3 g/j est apparue nettement plus efficace que celle de 1.5 g/j. II a cependant ete constate que meme a la dose reduite de 1.5 g/j, la frequence des crises etait encore significativement moindre qu'au depart. RESUMEN Se ha utilizado el gamma-vinyl GABA (GVG) en dosis de 3 g/dia durante 3 meses en 75 pacientes epilepticos que tenian, al menos, 2 ataques parciales complejos por mes. Se observo una reduccion de al menos 50% de los ataques en 41 pacientes, (55%). La frecuencia media mensual de ataques se redujo de 11.5 a 4 ataques/mes. El 25% de los enfermos mostraron una majoria general en sus actividades sin una reduccion significativa de los ataques. Los que mostraron algun tipo de respuesta entraron en la segunda fase de este estudio en la cual los enfermos fueron agrupados de modo aleatorio recibiendo 3 g/dia (28 enfermos) y 1.5 g/dia (25 enfermos) de GVG siguiendo un metodo doble-ciego. La dosis de 3 g/dia resulto ser claramente mas efectiva que la de 1.5 g/dia. Sin embargo es posible afirmar que, incluso con 1.5 g/dia de GVG, la frecuencia de ataques se redujo significativamente compareandola con la situacion basal. Los mareos fueron el sintoma colateral mas frecuentemente observado y se redujeron a medida que el tratamiento continuaba. En 3 casos los signos colaterales motivaron la interrupcion de la terapia con GVG. ZUSAMMENFASSUNG 75 Epilepsiekranke mit mindestens 2 komplexen Partialanfallen pro Monat wurden mit Gamma-Vinyl-GABA (GVG) 3 g/Tag 3 Monate lang behandelt. 41 Patienten (55%) zeigten eine Anfallsreduktion von 50% und mehr. Der Medianwert der mon-atlichen Anfallsfrequenz fiel von 11.5 auf 4 Anfalle pro Monat. 20% der Patienten boten eine Verbesserung ihres Gesamtzustandes ohne wesentliche Anfallsreduktion. Die Responder wurden in die 2. Phase der Studie aufgenommen, in der 28 randomisierte Patienten auf 3 g/Tag und 25 Patienten auf 1.5 g/Tag VGB unter Doppelblind-Bedingungen gesetzt wurden. Die Dosis von 3 g/Tag schien deutlich wirksamer als die von 1.5 g/Tag zu sein. Jedoch konnte selbst mit einer Dosis von 1.5 g/Tag die Anfallshaufigkeit signifikant verandert werden, verglichen mit den Ausgangswerten. Mudigkeit stellte die am haufigsten beobach-tete Nebenwirkung dar, die mit Dauer der Behandlung abnahm. Bei 3 Fallen zwangen die Nebenwirkungen zum Absetzen der GVG-Therapie.

Earlier studies suggest that low plasma uric acid level is a risk factor for Parkinson's disease (PD), and that uric acid associates with iron-binding proteins. We therefore decided to examine plasma uric acid levels and markers of peripheral iron metabolism in PD patients and healthy controls. For the study, 40 patients with PD and 29 controls underwent clinical screening, laboratory testing, and body mass index (BMI) measurement. The average consumption of different foodstuffs and dairy products was estimated. Plasma uric acid level was significantly lower in the patients than in the controls. There were no significant differences in the levels of plasma iron parameters, but plasma uric acid correlated strongly with serum ferritin both in the patient and the control group. The BMI was slightly lower in the patients compared with the controls despite equal daily calorie consumption. Plasma uric acid level is low in patients with PD, which may have implications for both the disease pathogenesis and treatment recommendations.