K. A. Sotaniemi

Poststroke Depression Correlates With Cognitive Impairment and Neurological Deficits

BACKGROUND AND PURPOSE The prevalence of poststroke depression is known to be high, but the knowledge of its neuropsychological correlates is limited. This 12-month prospective study was designed to evaluate the natural history of poststroke depression and to study its neuropsychological, clinical, and functional associates. METHODS We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65.8 years) with acute first-ever ischemic stroke. The patients underwent a neurological, psychiatric, and neuropsychological examination at 3 and 12 months after the stroke. The psychiatric diagnosis of depression was based on DSM-III-R-criteria. RESULTS Depression was diagnosed in 53% of the patients at 3 months and in 42% of the patients at 12 months after the stroke. The prevalence of major depression was 9% at 3 months and 16% at 12 months. There was an association between poststroke depression and cognitive impairment; the domains most likely to be defective in stroke-related depression were memory (P=0.022), nonverbal problem solving (P=0.039), and attention and psychomotor speed (P=0.020). The presence of dysphasia increased the risk of major depression. The depressive patients were more dependent in ADL and had more severe impairment and handicap than the nondepressive patients. CONCLUSIONS More than half of the patients suffer from depression after stroke, and the frequency of major depression seems to increase during the first year. In addition to dysphasia, poststroke depression is correlated with other cognitive deficits. We emphasize the importance of psychiatric evaluation of stroke patients.

Abnormal Heart Rate Variability as a Manifestation of Autonomic Dysfunction in Hemispheric Brain Infarction

BACKGROUND AND PURPOSE Abnormal heart rate variability is related to prognostically unfavorable ventricular arrhythmias and sudden arrhythmic death in coronary artery disease. Short-term electrocardiographic (ECG) recordings have shown similar abnormalities of heart rate variability in patients with acute stroke. However, there is no information regarding the clinical significance of these abnormalities and of heart rate variability in long-term ECG recordings in stroke. METHODS In this prospective study, we analyzed the time domain and frequency domain measures of heart rate variability from 24-hour ECG recordings in 31 consecutive patients with hemispheric brain infarction in the acute phase and at 1 and 6 months after the infarction and in 31 age- and sex-matched healthy control subjects. RESULTS All the measured components of heart rate variability, ie, standard deviation of RR intervals (P < .001), total power (P < .0001), very-low-frequency power (P < .0001), low-frequency power (P < .001), and high-frequency power (P < .05), were significantly lower than those of the control subjects in both the acute phase and 1 and 6 months later. Impaired heart rate variability correlated with the severity of neurological deficits and disability. In five patients with increased intracranial pressure due to large brain infarction, no relevant spectral components were found. CONCLUSIONS Hemispheric brain infarction seems to cause significant long-lasting damage to the cardiovascular autonomic regulatory system manifested as abnormalities of heart rate variability. Distorted heart rate variability in the acute phase of stroke may be prognostically unfavorable.

Natriuretic Peptides and Mortality After Stroke

Background and Purpose— Measurement of natriuretic peptides provides prognostic information in various patient populations. The prognostic value of natriuretic peptides among patients with acute stroke is not known, although elevated peptide levels have been observed. Methods— A series of 51 patients (mean age, 68±11years) with first-ever ischemic stroke underwent a comprehensive clinical examination and measurements of plasma atrial natriuretic peptides (N-ANP) and brain natriuretic peptides (N-BNP) in the acute phase of stroke. The patients were followed-up for 44±21 months. Risk factors for all-cause mortality were assessed. Control populations, matched for gender and age, consisted of 51 patients with acute myocardial infarction (AMI) and 25 healthy subjects. Results— Plasma concentrations of N-ANP (mean±SD, 988±993 pmol/L) and N-BNP (751±1608 pmol/L) in the stroke patients were at the same level as those in the AMI patients (NS for both), but significantly higher than those of the healthy subjects (358±103 pmol/L, P<0.001 and 54±26 pmol/L, P<0.01, respectively). Elevated levels of N-ANP and N-BNP predicted mortality after stroke (risk ratio [RR] 4.3, P<0.01 and RR 3.9, P<0.01, respectively) and after AMI (P<0.05), and remained independent predictors of death after stroke even after adjustment for age, diabetes, coronary artery disease, and medication (RR 3.9, P<0.05 and RR 3.7, P<0.05, respectively). Conclusion— Plasma levels of natriuretic peptides are elevated in the acute phase of stroke and predict poststroke mortality.

Enoxaparin vs heparin for prevention of deep-vein thrombosis in acute ischaemic stroke: a randomized, double-blind study

Objectives – To compare the efficacy, safety, and overall risk–benefit profile of enoxaparin and unfractionated heparin (UFH) prophylaxis of venous thromboembolic complications in patients with acute ischaemic stroke. Methods – Patients with ischaemic stroke resulting in lower‐limb paralysis lasting for at least 24 h and necessitating bedrest, were randomized within 48 h of the onset of stroke, and treated with enoxaparin (40 mg subcutaneously once daily) or UFH (5000 IU subcutaneously thrice daily) for 10 ± 2 days. Main outcome measures were deep‐vein thrombosis, pulmonary embolism (PE), death from any cause, intracranial haemorrhage including haemorrhagic infarction, or any other major bleeding. Results – Outcome events occurred within 3 months of stroke in 40/106 patients treated with enoxaparin (37.7%) and 52/106 patients treated with UFH (49.1%, P =0.127). Fewer patients treated with enoxaparin (14, 13.2%) than with UFH (20, 18.9%) had evidence of haemorrhagic transformation of ischaemic stroke. Conclusions – Enoxaparin administered subcutaneously once daily was as safe and effective as subcutaneous UFH given thrice daily in the prevention of thromboembolic events in patients with lower limb paralysis caused by acute ischaemic stroke.

Cardiovascular autonomic reflexes in brain infarction.

Background and Purpose Increased sympathetic activity is associated with cardiovascular complications in stroke, but the role of the parasympathetic nervous system has not been carefully outlined. In the present study our purpose was to assess quantitatively autonomic cardiovascular disturbances in brain infarction by measuring cardiovascular autonomic reflexes. Methods We studied the autonomic regulation of cardiovascular functions prospectively in 40 patients with brain infarction (acute phase, 1 month, and 6 months) and in 55 healthy control subjects by recording heart rate and blood pressure responses to normal and deep breathing, the Valsalva maneuver, tilting, and isometric work. Results In the acute phase, heart rate responses to normal breathing, deep breathing, the Valsalva maneuver, and tilting were significantly (P<.05) impaired in both hemispheric and brain stem infarctions, thus indicating hypofunction of the parasympathetic nervous system. At 1 month heart rate responses to normal breathing (brain stem, P<.05), the Valsalva maneuver (brain stem, P<.01), and tilting (hemispheric, P<.05) were still significantly lower than those of the control subjects, but at 6 months significant suppression of the response was found only in tilting (hemispheric, P<.05). Conclusions These findings suggest that in addition to the previously well‐established sympathetic hyperfunction, brain infarction also seems to cause parasympathetic hypofunction, which may be involved in cardiovascular and other known manifestations of autonomic failure associated with stroke. (Stroke. 1994;25:787‐792.)

Selegiline as initial treatment in de novo parkinsonian patients

To investigate the efficacy and safety of selegiline in the early phase of Parkinsons disease (PD), we carried out a placebo-controlled, double-blind, parallel trial. De novo PD patients were randomized to receive either selegiline (10 mg/d) or matching placebo. We continued selegiline or placebo until levodopa therapy became necessary and assessed the disability using three different rating scales at baseline, after 3 weeks, at 2, 4, 8, and 12 months, and at every 4 months thereafter. Fifty-two patients were eligible for the analysis, 27 in the selegiline group and 25 in the placebo group. The median duration of time before levodopa had to be initiated was 545 ± 90 days with selegiline and 372 ± 28 days with placebo (p = 0.03). Disability was significantly less in the selegiline group than in the placebo group up to 12 months. The period of time during which the mean total Columbia University Rating Scale score stayed below the baseline was used to express the initial symptomatic effect of the treatments. The difference in this initial improvement time between the two groups was about 3 months and did not alone explain the difference in the delay of the need to start levodopa therapy. Selegiline was well tolerated and there were no severe side effects. We conclude that selegiline delays the need to start levodopa in de novo PD patients, has symptomatic efficacy, and possibly retards the progression of the disease.

Autonomic nervous system disorders in stroke.

Disturbances of the autonomic nervous system are common in patients with various cerebrovascular diseases. They are attributed to damage of the central autonomic network, particularly in the frontoparietal cortical areas and in the brain stem, or to a disruption of the autonomic pathways descending from the hypothalamus via the mesencephalon, pons, and medulla to the spinal cord. The most common clinical problems include abnormalities in heart rate and blood pressure regulation, reflecting cardiovascular autonomic dysfunction, and asymmetric sweating with cold hemiplegic limbs, reflecting changes in the sudomotor and vasomotor regulatory systems. Bladder and bowel dysfunction and impotence are also frequent complaints after stroke, but the present knowledge concerning their prevalence and clinical significance is still limited. Cardiovascular autonomic dysfunction, which is mainly related to increased sympathetic activity, is most evident in the acute phase of stroke, whereas other autonomic disorders, such as abnormal sweating, are long-standing or even irreversible. In addition to the well-established sympathetic hyperfunction, abnormalities of the parasympathetic nervous system may also contribute to the autonomic imbalance after stroke. Reliable recognition of autonomic dysfunction using quantitative analysis methods is important, because these disturbances are not only subjectively disabling and uncomfortable, but they may also be prognostically unfavorable. Moreover, quantitative measurements also form the ground for successive treatment of various stroke-related autonomic disorders.Disturbances of the autonomic nervous system are common in patients with various cerebrovascular diseases. They are attributed to damage of the central autonomic network, particularly in the frontoparietal cortical areas and in the brain stem, or to a disruption of the autonomic pathways descending from the hypothalamus via the mesencephalon, pons, and medulla to the spinal cord. The most common clinical problems include abnormalities in heart rate and blood pressure regulation, reflecting cardiovascular autonomic dysfunction, and asymmetric sweating with cold hemiplegic limbs, reflecting changes in the sudomotor and vasomotor regulatory systems. Bladder and bowel dysfunction and impotence are also frequent complaints after stroke, but the present knowledge concerning their prevalence and clinical significance is still limited. Cardiovascular autonomic dysfunction, which is mainly related to increased sympathetic activity, is most evident in the acute phase of stroke, whereas other autonomic disorders, such as abnormal sweating, are long-standing or even irreversible. In addition to the well-established sympathetic hyperfunction, abnormalities of the parasympathetic nervous system may also contribute to the autonomic imbalance after stroke. Reliable recognition of autonomic dysfunction using quantitative analysis methods is important, because these disturbances are not only subjectively disabling and uncomfortable, but they may also be prognostically unfavorable. Moreover, quantitative measurements also form the ground for successive treatment of various stroke-related autonomic disorders.

Heart rate variability in patients with untreated Parkinson’s disease

The aim of this study was to evaluate cardiovascular responses as a marker of autonomic nervous system (ANS) disturbances in patients with untreated Parkinson’s disease (PD) and to assess the relationship between them and the clinical characteristics of PD. The ANS functions were investigated in 50 patients with PD and 55 healthy subjects by measuring standard cardiovascular autonomic reflexes and heart rate variability (HRV) at rest using spectral analysis (the autoregressive model and the fast Fourier transformation), the percentage of the counts of beat‐to‐beat variation greater than 50 ms and the fractal dimension. Significantly attenuated HRV and deficient blood pressure reaction to tilting were found in the PD patient group. The patients with hypokinesia/rigidity as the initial symptom of PD had a more pronounced HRV deficit than those with tremor onset. Untreated PD patients suffer significant failure in cardiovascular nervous system regulation, and in patients with hypokinesia/rigidity as their initial disease manifestation the risk of this ANS dysfunction is high. However, in the early stages of PD these changes did not reach significance at individual level.

Heart rate dynamics predict poststroke mortality

Background: Impaired cardiovascular autonomic regulation assessed by heart rate (HR) variability provides prognostic information in patients with heart disease as well as among elderly. Reduced HR variability has been described in stroke patients, but the prognostic significance of HR variability measures after stroke has not been studied. Methods: A series of 84 patients (mean age 59 ± 12years) with an acute first-ever ischemic stroke underwent a comprehensive clinical investigation, laboratory tests, and 24-hour EKG recordings and were followed up for 7 years (mean 83 ± 54 months). Various conventional and newer qualitative measures of HR variability were analyzed from the baseline 24-hour EKG. Risk factors for all-cause mortality were assessed. Results: During the follow-up, 33 (39%) patients died and 51 survived. Among all the variables analyzed, abnormal long-term HR variability measure power-law slope β (β < −1.5), reflecting an altered distribution of spectral characteristics over ultra and very low frequency bands, was the best univariate predictor of death (hazard ratio 4.5, 95% CI 2.2 to 9.5, p < 0.001). High age, poor Scandinavian Stroke Scale score, and abnormal short-term HR variability scaling measure (α) also predicted mortality in univariate analysis. In multivariate analysis, after adjustment for age, the only independent predictor of the risk of death was abnormal long-term power-law slope β (hazard ratio 3.8, CI 1.8 to 8.2, p < 0.001). Conventional HR variability measures showed no prognostic power. Conclusion: Abnormal long-term HR dynamics predict poststroke mortality. This measure may have value in the risk stratification of stroke patients.

Pharmacokinetics and metabolism of selegiline

Abstract– Selegiline is readily absorbed from the gastrointestinal tract. It is distributed rapidly into the tissues, including the brain. It is the L‐form of selegiline that is an active MAO‐B inhibitor, the D‐(+)‐form being 25 times less active. Selegiline is metabolised into L‐(−)‐desmethylselegiline (DES), L‐(−)‐amphetamine (A) and L‐(−)‐methamphetamine (MA), mainly in the liver. We measured the steady state concentrations of the metabolites in the serum and cerebrospinal fluid (CSF) of patients with Parkinsons or Alzheimers diseases who were on continuous selegiline therapy. The mean concentrations in serum and CSF were similar, and were not affected by the addition of levodopa. The mean concentrations of patients with Alzheimers or Parkinsons disease were 6.5±2.5 ng/ml for A, 14.7±6.5 ng/ml for MA and 0.9±0.7 ng/ml for DES. The metabolites of selegiline were excreted in urine, and the recovery as metabolites was 87%. Due to the stereospecificity and the low CSF concentrations of the (−)amphetamine metabolites during the therapy with 10 mg selegiline, these metabolites do not seem to contribute significantly to the clinical efficacy of selegiline.