Selegiline and blood pressure in patients with Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) frequently affects both the extrapyramidal system and the autonomic nervous system (ANS), the latter also being sometimes disturbed by PD medications. Specifically selegiline is known to disturb cardiovascular ANS functions and may cause or enhance orthostatic hypotension. METHODS: In order to study the effect of the withdrawal of selegiline on the regulation of blood pressure (BP) in advanced PD, an orthostatic test was performed in 14 PD patients with wearing-off before the morning levodopa dose and thereafter repetitively at 1-h intervals for up to 4 h. A Unified Parkinson's Disease Rating Scale motor score evaluation was also carried out hourly. The tests were repeated after a 4-week selegiline washout period. RESULTS: Selegiline withdrawal decreased systolic BP significantly during the on-stage in a supine position as well as during the orthostatic test. The initial drop of BP in the orthostatic test was significantly smaller after selegiline withdrawal. The heart rate remained unaffected.

Economic burden and quality of life impairment increase with severity of PD.

PURPOSE: To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson's disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. CONCLUSIONS: There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.

Twelve-month safety of entacapone in patients with Parkinson's disease.

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.

Neurological complications of drug abuse: pathophysiological mechanisms.

Drug abuse is associated with a variety of neurological complications. The use of certain recreational drugs shows a marked temporal association with the onset of both haemorrhagic and ischaemic strokes, the majority of which develop within minutes to 1 h after the administration of the index drug. Delayed onset of stroke has also been observed. Acute, severe elevation of blood pressure, cardiac dysrhythmias, cerebral vasospasm, vasculitis, embolization due to infective endocarditis or dilated cardiomyopathy, embolization due to foreign material injected with the diluents under non-sterile conditions and 'street drug' contaminants with cardiovascular effects have been suggested as possible underlying mechanisms. Rupture of aneurysms and arteriovenous malformations have been detected in up to half of the patients with haemorrhagic stroke due to cocaine abuse. The less common findings reported have included a mycotic cerebrovascular aneurysm in a patient with infective endocarditis and haemorrhagic stroke. In addition to stroke, cocaine seems to provoke vascular headache. Seizures precipitated by recreational drug abuse are usually caused by acute intoxication in contrast to the withdrawal seizures encountered in subjects with alcohol abuse. Movement disorders and cerebral atrophy correlating with the duration of abuse have been described. Snorting of organic solvents may cause encephalopathy. Cases of spongiform leukoencephalopathy in heroin addicts have also been reported. Peripheral neuropathy is occasionally precipitated by drug poisoning after intravenous administration. Impurities of the drug, risky administration techniques, and the use of mixtures of various drugs, frequently with simultaneous alcohol drinking, should be taken into account when assessing the background of the adverse event as well as the overall lifestyle of the addicted subjects.

Dye dilution and oximetry for detection of patent foramen ovale.

OBJECTIVES: Patent foramen ovale (PFO) is a risk factor for stroke of undetermined (cryptogenic) origin. Low cost and non-invasive bedside tests for detection of PFO are needed as alternatives to contrast transesophageal echocardiography. We investigated whether dye dilution curves and oximeter recordings are useful for detecting PFO and what is the prevalence of PFO in patients with cryptogenic stroke determined with these bedside methods. We also studied whether stroke risk factors, number of brain lesions, and stroke recurrence rates were different in patients with an unexplained stroke with and without PFO. MATERIAL AND METHODS: Dye dilution curves and oximeter recordings with non-invasive earpiece apparatus were obtained in 59 patients aged under 50 years who had had a cryptogenic brain infarction. The number of ischemic lesions in the brain was counted by MRI. RESULTS: PFO was found in 24 (41%) of 59 patients. There was a 100% concordance in results obtained by dye dilution and by oximetry. Risk factors for stroke were similar in subjects with PFO and those without PFO. No significant association was found between PFO and Valsalva-like activity at stroke onset. Those with PFO did not have more ischemic lesions detected by MRI nor did they have more recurrent ischemic episodes. CONCLUSION: Dye dilution and oximetry are cheap and useful methods for detection of PFO and could be used for screening of the risk of paradoxical embolism. Because these 2 methods were not compared with the golden standard, transesophageal echocardiography, the specificity and sensitivity of the tests remain unsettled.

Lifestyle-associated risk factors for acute brain infarction among persons of working age.

BACKGROUND AND PURPOSE: This study was designed to identify whether cigarette smoking, alcohol drinking, obesity, and use of oral contraceptives are independent risk factors for brain infarction among persons of working age. METHODS: Health habits and previous diseases of 506 patients (366 men and 140 women aged 16 to 60 years) with acute first-ever symptomatic brain infarction were compared with those of 345 hospitalized control patients (219 men and 126 women) who did not differ from case subjects in respect to day of onset of symptoms or acuteness of disease onset. With the use of stepwise logistic regression, the variables for which the simultaneous risks of acute brain infarction were tested by sex were age, amount of alcohol consumed within 24 hours and 1 week before the illness, heavy drinking, smoking status, current smoking, cardiac disease, hypertension, diabetes, hyperlipemia, migraine, body mass index, and, in women, current use of oral contraceptives. RESULTS: Intake of > 40 g ethanol within the 24 hours preceding the onset of illness increased the risk for acute brain infarction both among men (P < .001) and women (P < .01) independently from other risk factors. Other significant independent risk factors for brain infarction among men were hypertension (P < .001), cardiac disease (P < .01), current smoking (P < .01), diabetes (P < .05), and history of migraine (P < .05) and among women, current use of oral contraceptives (P < .01) and current smoking (P < .05). CONCLUSIONS: Recent heavy drinking of alcohol, hypertension, cardiac disease, current smoking, diabetes, and history of migraine among men, and recent heavy drinking of alcohol, current use of oral contraceptives, and current smoking among women, seem to be independent risk factors for acute brain infarction.

Carotid arterial dissection as a cause of severe brain infarction in young adults.

OBJECTIVES: To investigate the occurrence of cervicocerebral arterial dissection in young adults, we examined the etiology of first-ever brain infarction and the timing of angiography. METHODS: One hundred eighty-four subjects with first stroke aged 16 to 49 years, admitted to the Helsinki University Hospital between 1983 and 1990 were included. Seventy-eight percent of the angiographies were performed more than 1 week after the onset of stroke symptoms. RESULTS: We identified 19 (10%) subjects with carotid arterial dissection and none with vertebral arterial dissection. Mortality attributed to ischemic stroke caused by carotid arterial dissection was high (26%). With longer time between onset of stroke symptoms and angiography, dissection was a rarer finding (P < .01), and there were more angiographies with no findings (P < .05). Trauma (P < .001) and headache (P < .05) preceded onset of stroke more frequently in these patients than in others. CONCLUSIONS: Prompt imaging of the cervicocerebral arteries is indicated if the patient has preceding trauma or complains of headache and/or neck pain.

Weekend and holiday increase in the onset of ischemic stroke in young women.

BACKGROUND AND PURPOSE: Chronobiological analyses of stroke onset may throw some light on the mechanisms that trigger stroke. Observations may generate new hypotheses for identifying significant causal relationships. METHODS: In the present study, both the circadian and the weekend and holiday versus workday times of the onset of ischemic cerebral infarction were determined for 723 consecutive subjects, aged 16 to 60 years, who were admitted for hospital treatment in the acute phase without any selection. RESULTS: Among young adults (16 to 40 years) and women, more infarctions occurred during weekends and holidays than were expected. Young women in particular had an increased risk for brain infarction during weekends and holidays (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.26 to 3.63). In a multivariate analysis, age of 16 to 30 years (OR, 3.13; 95% CI, 1.57 to 6.50), female sex (OR 1.71; 95% CI, 1.12 to 2.63), and recent drinking of alcohol (P < .01) were associated with the onset of brain infarction during weekends and holidays, whereas current cigarette smoking was associated with the onset of brain infarction during workdays (P < .001). A morning increase in the onset of brain infarction was observed among middle-aged people during both weekends/holidays and workdays. Among young adults, however, an evening increase was also seen during weekends/holidays and workdays. CONCLUSIONS: We found that young adults and women are frequently stricken by brain infarction during weekends and holidays and that the circadian distribution of the onset of brain infarction among young adults is different from that of middle-aged people. These observations suggest that there may be stroke-triggering activities that are associated with lifestyle.

Non-amoeboid locomotion of cultured microglia obtained from newborn rat brain.

The movements of cultured microglia obtained from newborn rat brain were examined by video enhanced-differential interference contrast (VEC-DIC) microscopy. Active microglia measured 9.03 +/- 1.06 microns in diameter (mean +/- SD, n = 33; range, 7.03-10.36 microns). The microglia appeared to become smaller with spread of lamellipodia. The short axis of actively moving microglia measured 7.03 +/- 0.49 microns (n = 7). The lamellipodia were thin, transparent and developed rapidly around the cell body (maximal speed of extension, 4 or 5 microns/s). When shear stress from the medium was applied to the surface of cultured cells, the microglia swam with flat lamellipodia serving as sails in the stream. Spontaneous non-amoeboid movements of microglia were observed: they pivoted, circled and marched in various directions using their lamellipodia. The angular speed of rotation was maximally 3 degrees/s. In 5 marching cells, the average speed (distance/s) was calculated at 1.01 +/- 0.54 microns/s (ca. 60 microns/min or 3.6 microns/h).

Recent alcohol consumption, cigarette smoking, and cerebral infarction in young adults.

BACKGROUND AND PURPOSE: The role of recent heavy drinking of alcohol as a risk factor for ischemic brain infarction is unclear. We investigated this problem in young adults, in whom even a thorough workup often fails to reveal any predisposing factor. METHODS: This was a hospital-based case-control study comprising 75 consecutive subjects aged 16 to 40 years with first-ever ischemic brain infarction and 133 control subjects from the same hospital who were group-matched with the case patients for age, sex, day of the onset of symptoms, and acuteness of disease onset. RESULTS: Multiple logistic regression analysis showed that alcohol intake exceeding 40 g of ethanol within the 24 hours preceding disease onset was a significant independent risk factor for brain infarction among both men (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.8 to 20.3) and women (OR, 7.8; 95% CI, 1.0 to 60.8). Cigarette smoking was not found to be an independent risk factor in the model, whereas among men arterial hypertension was (OR, 6.2; 95% CI, 1.5 to 24.7). CONCLUSIONS: We conclude that very recent alcohol drinking, particularly drinking for intoxication, may trigger the onset of brain infarction in young adults and that there might be a variety of mechanisms behind this effect.