Subtle cognitive deficits after cerebellar infarcts.

The role of the cerebellum in cognitive functions has been under debate. We investigated the neuropsychological functioning of patients with cerebellar lesions (infarcts) and evaluated the significance of laterality in cognitive symptoms. Twenty-six patients with exclusive cerebellar lesions as verified by clinical and neuroradiological findings underwent a neuropsychological assessment at the acute stage and at 3 months. Their performance was compared with 14 controls, also assessed twice. The focus was on four domains: visuospatial/motor functions, episodic memory, working memory and attentional shifting/execution. Both groups improved over time. Statistical differences emerged in tests in the visuomotor domain as well as in the episodic and working memory domains. Patients with left cerebellar lesion were slow in a visuospatial task, whereas those with right cerebellar lesions had verbal memory difficulty compared with controls. By 3 months, 77% of the patients had returned to work, and only one had cognitive impairment and did not return to work. Our results indicate that cerebellar infarcts may result in subtle cognitive changes perhaps primarily related to working memory deficit. The symptoms may be mediated by the contralateral cortical hemisphere, left cerebellar infarcts producing mild right hemispheral dysfunction and right cerebellar infarct producing mild left hemispheral dysfunction.

Prevalence of spinal cord injury in Helsinki.

STUDY DESIGN: Retrospective register-based epidemiological study. OBJECTIVE: To estimate the prevalence rate of persons with spinal cord injury (SCI) with special reference to ASIA Impairment Grade A-D. SETTING: Helsinki, Finland. METHODS: Cases were identified using the registers of the Kapyla Rehabilitation Centre, Helsinki University Central Hospital and the local organization for the disabled. Local health centres were informed about the study, residential service houses were contacted, and announcements were published in patient magazines. RESULTS: A regional population was found to have a prevalence rate of 28/100,000 inhabitants with SCI (ASIA Impairment Scale A-D). CONCLUSION: The prevalence rate in this study is consistent with the data published in other Nordic countries. SPONSORSHIP: The Finnish Cultural Foundation.

Normal intelligence in children with prenatal exposure to carbamazepine.

OBJECTIVE: To investigate the effect of antiepileptic drugs, especially carbamazepine and valproate, on intelligence in prenatally exposed children of mothers with epilepsy. METHODS: Intelligence of 182 children of mothers with epilepsy (study group) and 141 control children was tested in a blinded setting at preschool or school age using Wechsler Preschool and Primary Scale of Intelligence-Revised or Wechsler Intelligence Scale for Children-Revised. Data on maternal antiepileptic treatment and seizures during pregnancy were gathered prospectively. The study group represented approximately 50% of the children born to mothers with epilepsy in Uusimaa province during 1989 through 1994. One hundred seven children were exposed to antiepileptic monotherapy: 86 to carbamazepine and 13 to valproate. Thirty children were exposed to polytherapy: 23 combinations included carbamazepine, and 17 included valproate. The median maternal doses and blood levels during the second half of pregnancy were 600 mg and 26 micro mol/L for carbamazepine and 950 mg and 300 micro mol/L for valproate. RESULTS: The mean verbal and nonverbal IQ scores in the children exposed in utero to carbamazepine monotherapy were 96 (95% CI, 93-100) and 103 (95% CI, 100-106). They did not differ from control subjects, whose mean verbal and nonverbal IQ scores were 95 (95% CI, 92-97) and 102 (95% CI, CI, 100-105). Significantly reduced verbal IQ scores were found in children exposed to valproate (mean, 82; 95% CI, 78-87) and to polytherapy (mean, 85; 95% CI, 80-90) compared with the other study group children and control subjects. CONCLUSIONS: Carbamazepine monotherapy with maternal serum levels within the reference range does not impair intelligence in prenatally exposed offspring. Exposures to polytherapy and to valproate during pregnancy were associated with significantly reduced verbal intelligence. The independent effects of valproate remain unconfirmed because the results were confounded by low maternal education and polytherapy.

Fasting serum insulin and lipid levels in men with epilepsy.

BACKGROUND: Previous studies suggest that obese women taking valproate (VPA) for epilepsy are insulin resistant. OBJECTIVE: To assess the effects of antiepileptic drugs on serum insulin and lipid levels in men with epilepsy. METHODS: Body mass index (BMI) and fasting serum concentrations of insulin and lipids were measured in 102 men with epilepsy who were treated with VPA, carbamazepine (CBZ), or oxcarbazepine (OXC) monotherapy. Thirty-two healthy men served as control subjects. RESULTS: Obesity was not more common among VPA-treated men than among other men with epilepsy or the control subjects. However, the obese VPA-treated men had higher serum insulin levels (p < 0.001) than the obese control subjects despite similar BMI. CBZ and OXC did not have any significant effect on any of the measurements. Fasting serum insulin concentrations above the normal range were observed in seven obese VPA-treated patients (35%) but in only one obese control subject (5%). Five obese VPA-treated patients (25%) and one obese control subject (5%) had serum triglyceride levels above the normal range, and a low high-density lipoprotein/total cholesterol ratio was observed in two obese VPA-treated patients (10%). CONCLUSIONS: Obese valproate-treated men have high serum insulin levels, indicating insulin resistance. Moreover, some of the valproate-treated men cluster cardiovascular risk factors such as obesity, hyperinsulinemia, and elevated serum triglyceride concentrations. CBZ and OXC do not seem to have any significant effects on serum insulin or lipid levels in men with epilepsy.

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy.

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.

Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy.

BACKGROUND: Recent observations have indicated that reproductive endocrine disorders are common among women taking valproate (VPA) for epilepsy, but it is not known whether respective abnormalities develop in men taking VPA for epilepsy. Carbamazepine (CBZ) may induce endocrine disorders in men with epilepsy, but the endocrine effects of oxcarbazepine (OXC) are not known. METHODS: Reproductive endocrine function was evaluated in 90 men taking VPA (n = 21), CBZ (n = 40), or OXC (n = 29) as monotherapy for epilepsy and in 25 healthy control men. RESULTS: Twelve men (57%) taking VPA had increased serum androgen levels. The mean serum level of androstenedione was high in patients taking VPA. Serum levels of dehydroepiandrosterone sulfate were low, and serum concentrations of sex hormone-binding globulin (SHBG) were high in men taking CBZ. The endocrine effects of OXC seemed to be dose-dependent, because serum hormone levels were normal in patients with low OXC doses (< 900 mg/day), but serum concentrations of testosterone, gonadotropins, and SHBG were high in patients with a daily OXC dose > or = 900 mg. CONCLUSIONS: VPA increases serum androgen concentrations in men with epilepsy. The endocrine effects of CBZ and OXC were different, because CBZ appears to decrease the bioactivity of androgens, whereas OXC does not.

Decreased severity of brain infarct can in part explain the decreasing case fatality rate of stroke.

BACKGROUND AND PURPOSE: Case fatality rates for stroke has declined in most Western industrialized countries during recent decades. One possible explanation for this is a decrease in the severity of stroke symptoms. We therefore sought evidence for a change in stroke severity and its relationship with case fatality rates. METHODS: We compared the severity of symptoms among first-ever stroke patients in 2 population-based prospective stroke registers maintained during 1972 to 1973 and 1989 to 1991 in Finland. Patients who were evaluated by study assistants or the investigator during the first week after the onset of symptoms were included in the study, and their severity of symptoms was assessed with the use of comparable scales modified from the Scandinavian Stroke Scale. RESULTS: A total of 244 and 594 patients were registered, and a portion of them (155 [63.5%] and 360 [60.6%]) were included in the analyses in the registers for Espoo-Kauniainen from 1972 to 1973 and for 4 separate districts in Finland from 1989 to 1991, respectively. The death rates during the first week among those who were not included did not differ between the registers. The severity of symptoms decreased significantly between the registers in both patients with brain infarct or intracerebral hemorrhage but not in those with subarachnoid hemorrhage. The severity of symptoms was an independent factor of case fatality at 1 month. CONCLUSIONS: The severity of symptoms of brain infarcts has decreased and can in part explain the decreased case fatality rate of stroke in Finland. However, the change in patients with intracerebral hemorrhage may be overestimated due to undiagnosed intracerebral hemorrhages in the first register resulting from the lack of brain CT.

Post-stroke depression and functional recovery in a population-based stroke register. The Finnstroke study.

Post-stroke depression and functional outcome were examined in a population-based stroke register active in four different districts (total population, 134 804) in Finland. Five hundred and ninety four first time strokes were registered. Beck's depression inventory (BDI), with ten as the cutoff point for depression, was applied to 321 of 423 survivors after three months and to 311 of 390 survivors after 12 months. Functional outcome was measured with the Barthel Index (BI) and the Rankin Scale (RS). One hundred and fifty one of 321 (47.0%) and 147 of 311 (47.3%) patients were depressed after three and 12 months, respectively. Depression at three months was associated with poor functional outcome at the one-year follow-up (P = 0.001 for the BI and the RS). On the other hand, poor functional outcome at three months was associated with depression after one year (P = 0.004 and 0.002 for the BI and the RS, respectively). Patients who were depressed at three months were more often in institutional care between three and 12 months later than non-depressed patients (P = 0.005). Post-stroke depression is associated with poor functional recovery of patients. If depression were diagnosed and treated early, it might help patients to recover more completely and/or faster, which could save community healthcare resources by avoiding or shortening the time of institutional care or reducing the need for home care.

Modification of neuromagnetic cortical signals by thalamic infarctions.

Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-channel neuromagnetometer from 7 patients, who had small thalamic infarctions in the region of the left anterior tuberothalamic artery and associated memory defects. In contrast to healthy control subjects, with dominant rhythmic activity at 10.6 +/- 0.6 Hz in the parieto-occipital region, the spectral maximum in the patients was at 8.9 +/- 0.4 Hz. Abnormal acceleration of rhythmic activity was also observed bilaterally in rolandic areas. Our findings imply that lesions of non-specific thalamic nuclei may disturb human brain rhythms in widespread cortical areas. 'Mismatch responses' to deviant tones (1.1 kHz) among standards (1.0 kHz), suggested to reflect sensory auditory memory in healthy subjects, were absent in 2 patients, markedly decreased in 3, and normal in 2, implying that pathways passing through the anteromedial thalamus contribute to modulation of these responses. We conclude that local unilateral lesions in the anteromedial thalamus may cause extensive, bilateral alterations in the brain's electric activity.

Depression after stroke: results of the FINNSTROKE Study.

BACKGROUND AND PURPOSE: We compared the incidence and severity of depression at 3 and 12 months after stroke in patients and their chief caregivers (spouses, 63%; children, 37%) in four districts of Finland, two with and two without after-hospital-discharge interventional programs (outpatient rehabilitation and activities of the local divisions of the Finnish Heart Association [FHA]). A population-based stroke register was used, and factors influencing depression were analyzed. METHODS: A stroke register of patients recruited over 2 years in four different districts (total population, 134804) in Finland; 594 first-ever strokes were registered. Beck's Depression Inventory (BDI), with 10 as the cutoff point for depression, was applied to 321 of 423 survivors and 195 caregivers at 3 months and to 311 of 390 survivors and 184 caregivers at 12 months in the districts with and without interventional programs. RESULTS: At 3 months, fewer patients in the districts with active programs (41%) were depressed than in the control districts (54%) (odds ratio, 0.59; 95% confidence interval, 0.37 to 0.94), and the difference was maintained at 12 months (42% versus 55%) (odds ratio, 0.55; 95% confidence interval, 0.34 to 0.88). Univariate risk factors for depression at 3 months were female sex and severe prognostic score at the onset of stroke (< or = 14 points) on the Scandinavian Stroke Scale (SSS). Only SSS prognostic score and age emerged as significant independent contributors to depression on both linear and logistic multivariate analyses. There was no significant difference in the depression rate of caregivers between districts with active programs (42%) and those without such programs (41%) at 3 months; at 12 months the results were the same (39% in districts with active programs versus 42% in those without such programs). However, at 12 months there were significantly more severely depressed caregivers in districts without active programs than in districts with such programs (P.036). Poor Rankin scale score (grades III through V) and severe SSS long-term score (< or = 42 points) at 3 months among the patients were associated with depression of the caregivers at 3 months in the univariate analysis. Poor Rankin Scale score of the patients was independently associated with the depression of their caregivers at 3 months on multivariate logistic regression analysis. CONCLUSIONS: Depression was common among stroke survivors and among their caregivers at 3 months, and its rate did not decrease at 1-year follow-up. The lower depression rate in districts with active programs compared to those without supports the idea that outpatient rehabilitation and support provided by local divisions of the FHA may be an effective way of decreasing the rate of depression after stroke.

Spin-echo MRI of chronic intracerebral haematomas.

Our purpose was to characterise the MRI appearances of clinically non-neoplastic chronic intracerebral haematomas (ICH). We examined 25 patients with a history of clinically non-neoplastic 0.5-to 1.5-year-old ICH who underwent prospective follow-up 1.0-T spin-echo MRI of the brain. On T1-weighted images most lesions gave lower signal than white matter and were isointense with cerebrospinal fluid (CSF). On T2-weighted images most were either totally low-signal and slit-like, or had a high-signal centre and a low-signal margin. The low-signal (haemosiderin) rim showed areas of discontinuity in 7 cases. Of 24 lesions, 4 showed small enhancing areas on contrast-enhanced images. In 10 cases the brain parenchyma surrounding the lesion showed high-signal on T2- and low signal on T1-weighted images, probably representing encephalomalacia. In 20 cases enlargement of a nearby CSF space was observed, and 14 cases showed atrophy of the brain stem ipsilateral to the lesion. We thus found more variation on MRI of clinically non-neoplastic chronic ICH than previously described.

Declining incidence and mortality rates of stroke in Finland from 1972 to 1991. Results of three population-based stroke registers.

BACKGROUND AND PURPOSE: We aimed to determine trends in stroke incidence, mortality rates, case-fatality rates, and their relation in Finland. METHODS: We compared the results of three population-based stroke registers that included first-ever strokes in people aged > or = 15 years. Two registers were kept in Espoo-Kauniainen, the first in 1972 to 1973 (EK 72-73) and the second in 1978 to 1980 (EK 78-80). The present register of the Finnish Heart Association (FHA 89-91) was kept in four districts in Finland in 1989 to 1991. RESULTS: The age-adjusted incidence rates were 240.9, 174.4, and 191.6, and the 1-year mortality rates were 121.9, 77.0, and 65.3 in the EK 72-73, EK 78-80, and FHA 89-91 registers, respectively. The overall decline from 1972 to 1991 was 20% in the stroke incidence rate and 46% in the stroke mortality rate. One-month case-fatality rates decreased from 34.8% to 29.4% in the EK 72-73 and EK 78-80 registers and to 23.3% in the present register. CONCLUSIONS: The decline in the stroke incidence rate during the 1970s stabilized during the late 1980s and early 1990s; however, the case-fatality rate is still decreasing. Their combined effects may explain the continuing decline in stroke mortality.

Psychosocial and health status in stroke survivors after 14 years.

BACKGROUND AND PURPOSE: Most studies of long-term survival and assessment of health status in survivors of stroke are hospital based and are often based only on a relatively short follow-up. This study was aimed at evaluating survival of acute stroke after 14 years. We also assessed psychosocial and health status among the long-term stroke survivors. METHODS: This study is a follow-up of the Finnish part of the collaborative World Health Organization Stroke Study that took place during 1972 through 1974. All survivors were interviewed by telephone after being sent a structured questionnaire approximately 14 years after the initial stroke attack. Information on clinical history, socioeconomic situation, self-reported functional capacity, psychosomatic status, perceived mental status, and perceived health was collected. RESULTS: Of the 1241 persons who had been entered in the stroke register from 1972 through 1974, 241 (19.4%) were still alive after 14 years. Participation rate in the telephone interview was 83.4%. Over 80% of all stroke survivors lived at home or with relatives at the time of interview. Functional capacity was good in about two thirds of the stroke survivors. Only 10% to 15% of all respondents felt depressed. About half of both men and women aged 64 years or younger perceived their health as good, while only 25% of men aged 65 years or over did. CONCLUSIONS: Most stroke survivors did not need institutionalized care in the long term. Although a large proportion of them suffered from various somatic diseases, their functional capacity was found to be good.

Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease.

A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.

Epilepsy after stroke.

A retrospective follow-up of 200 consecutive stroke patients [ischemic brain infarction (IBI) 157, intracerebral hemorrhage (ICH) 20, subarachnoid hemorrhage (SAH) 23] who were in need of ambulatory rehabilitation was conducted for a mean period of 40 months after stroke. Epilepsy developed in 33 (17%) patients. The occurrence of epilepsy was 14% in IBI, 15% in ICH, and 35% in SAH. Significantly more patients developed epilepsy in the SAH group than in the IBI group (8 of 23 vs. 22 of 157, p less than 0.05). Of the 33 patients, 15% had their first seizures within the first 2 weeks after stroke, and 55% developed epilepsy in 6 months. Forty-eight percent of the patients had generalized seizures. Antiepileptic drug (AED) treatment was started in 28 of 33 patients, of whom 17 still had seizures during follow-up. Epilepsy was an important consequence of stroke among patients who needed rehabilitation, especially in SAH patients. In most, this was due to arterial spasm leading to IBI.

Pharmacokinetics and metabolism of selegiline.

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 Parkinson's or Alzheimer's 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 Alzheimer's or Parkinson's 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.

Quality of life 4 years after stroke.

The quality of life for 46 stroke survivors under the age of 65 years in a stroke register was studied 4 years after their first stroke. A questionnaire covering four domains of life (working conditions, activities at home, family relationships, and leisure time activities) was used for investigation of the quality of life. The results showed that in spite of a good recovery in terms of discharge from the hospital, activities of daily living, and return to work, the quality of life of most patients (83%) had not been restored to the prestroke level. Deterioration among the several domains of life ranged from 39% to 80%, the lowest being in the domain of activities at home and the highest in the domain of leisure time activities. Hemispheral localization of the lesion, paresis, coordination disturbances, and especially subjective tendency to depression were highly correlated with a deterioration in the quality of life. Dependence in activities of daily living and an inability to return to work were also associated with the lack of restoration. Our results suggest that much more attention should be paid to the quality of life of stroke patients.