Reijo J. Marttila

Oxygen toxicity protecting enzymes in Parkinson's disease: Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus

Oxygen-derived toxicity has been suggested as being involved in the pathogenesis of Parkinsons disease. Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase provide the enzymatic defence against oxygen toxicity. The activities of these enzymes were measured in peripheral blood leucocytes, cerebrospinal fluid and in different brain regions from patients with idiopathic Parkinsons disease and from controls. There was no indication of a generalized defect in any of these enzymes in Parkinsons disease. The brain activities of catalase, glutathione peroxidase and glutathione reductase were also comparable to those of the controls. An increased superoxide dismutase-like activity was observed in several regions of parkinsonian brains, including the temporal cortex, thalamus and red nucleus. However, the most pronounced increase occurred in the substantia nigra and basal nucleus. This may be due to an increase of the superoxide dismutase activity or be a result of the presence of a compound with superoxide dismutase-like activity, and may reflect the involvement of radical-induced cell damage in the pathogenesis of Parkinsons disease.

Etiology of aseptic meningitis and encephalitis in an adult population

Objective: To investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods. Methods: Consecutive patients (ages ≥16) with aseptic meningitis or encephalitis treated in Turku University Hospital, Finland, during 1999 to 2003 were included in the study. Microbiologic tests were performed, including CSF PCR tests for enteroviruses, herpes simplex virus (HSV) 1, HSV-2, and varicella zoster virus (VZV), as well as serum and CSF antibody analysis for these viruses. Antibody testing was also performed for other pathogens commonly involved in neurologic infections. Virus culture was performed on CSF, fecal, and throat swab specimens. Results: Etiology was defined in 95 of 144 (66%) patients with aseptic meningitis. Enteroviruses were the major causative agents (26%), followed by HSV-2 (17% of all, 25% of females) and VZV (8%). Etiology was identified in 15 of 42 (36%) patients with encephalitis, VZV (12%), HSV-1 (9%), and tick-borne encephalitis virus (9%) being the most commonly involved pathogens. Etiologic diagnosis was achieved by PCR in 43% of the patients with meningitis and in 17% of those with encephalitis. Conclusions: Enteroviruses and HSV-2 are the leading causes of adult aseptic meningitis, and PCR is of diagnostic value. However, in most cases of encephalitis, the etiology remains undefined.

Survival and cause of death in Alzheimer's disease and multi-infarct dementia.

ABSTRACT Survival and causes of death of 218 patients with Alzheimers disease (AD) and of 115 patients with multi‐infarct dementia (MID) were examined. The patients were originally found in a community‐based epidemiological survey of dementia, and all patients with AD or MID alive on the prevalence day were included. The 6‐years survival rate for AD was 21.1% vs. the expected rate 48.5%, that for MID 11.9% vs. 45.2% expected. A comparison of relative survival rates suggested that MID carries a less favorable survival prognosis than AD. The mean durations were: AD 5.7 years and MID 5.2 years; median duration being 5 years in both diseases. The excess mortality in both AD and MID was independent of age. In AD, the survival rate decreased with increasing severity of dementia, while in MID the mortality was the same regardless of the severity of the dementia. The dementia disorder was the underlying cause of death in 68% of AD patients, and in 38% of MID patients, bronchopneumonia being the most frequent immediate cause of death in both groups. As a cause of death, acute cerebrovascular accidents occurred more often in MID patients than in the general population of comparable age. Malignant diseases were less frequent as a cause of death in both dementia groups than in the general population.

Epidemiology of dementia in a Finnish population

An epidemiological study of dementia was carried out in the city of Turku (population 164,568) in Finland. A total of 421 patients with moderate to severe dementia were found. Degenerative dementia, i.e. presenile and senile dementia, was present in 218 patients (51.8 %), and in 152 patients (36.1 %) the dementia was associated with arteriosclerosis, including multi‐infarct and combined dementia. The prevalence rate of dementia, all types, was 256 per 100,000 population, and 1,961 per 100,000 population over 65 years old. The age‐specific prevalence rates of dementia increased with advancing age from 0.1 % in the age group 55–64 years to 11 % in the age group over 85 years. The peak annual incidence rate for all types of dementia was 58 per 100,000 population, and 447 per 100,000 population over 65 years old. Both prevalence and incidence figures suggested a female preponderance in dementia of degenerative origin and in dementia with associated arteriosclerosis.

DEMENTIA IN PARKINSON'S DISEASE

The occurrence of dementia in patients with Parkinsons disease was studied in a Parkinsonian population consisting of all traceable patients residing in a defined area. the prevalence of dementia was found to be 29 per cent in 444 patients studied. the frequency of dementia increased with advancing age and the patients showing signs of clinical arteriosclerosis were more often demented than the patients without arteriosclerosis. There was, however, an evident association between the stage of the disease and the frequency of dementia. the most severely disabled patients displayed dementia more often than the mildly affected, both among the patients with and without arteriosclerosis. the demented patients showed significantly more severe rigidity and hypokinesia when compared with the non‐demented. Increasing severity of rigidity and hypokinesia, in particular, was found to have a positive correlation with the degree of dementia. the association between dementia and the degree of motor involvement is considered to suggest the role of subcortical structures in the pathophysiology of dementia in Parkinsons disease.

Essential tremor in a Finnish population.

A two‐phase epidemiological study of essential tremor was carried out by investigating a rural population aged over 40 years in 2 municipalities in southwestern Finland. In the first phase, the subjects answered a questionnaire as to whether they had experienced tremor during the month preceding the inquiry. In the second phase, the persons who had tremor often or fairly often, were examined clinically. The total prevalence of essential tremor, calculated on the basis of clinically established cases, was 55.5‰ of the population aged over 40 years. The disease became more prevalent with advancing age and was, with the exception of the oldest age‐group, more common in men than in women.

Changing epidemiology of Parkinson’s disease in southwestern Finland

Objective: Investigation of the epidemiology of PD in southwestern Finland in 1992 (population 196,864), including urban and rural areas, with a comparison with a similar study, done in the same area in 1971, to evaluate the temporal pattern. Methods: Community-based method of patient ascertainment with personal investigation of cases. Results: The age-adjusted prevalence (to the Finnish general population in 1991) was 139 per 100,000 population in 1971 and 166 in 1992. Prevalence ratio for PD in men versus women was 1.2 (NS) in 1971 and 1.7 in 1992 (p < 0.001); in the rural versus urban populations the prevalence ratio was 0.8 (NS) in 1971 and 1.3 in 1992 (p = 0.013). The age-specific prevalence rates showed a male preponderance in all age groups in 1992 and a rural preponderance in the age groups over 60 years. In 1992, compared with 1971, the male and rural preponderance occurred in the age groups over 70 years. The age-adjusted incidence was 15.7 per 100,000 population in 1971 and 14.9 in 1992. Relative risk for PD in men versus women was 0.9 (NS) in 1971 and 1.9 (p < 0.001) in 1992, and in rural versus urban populations 1.4 (p = 0.093) in 1992. Conclusions: A very significant male and a significant rural predominance, not seen in 1971, suggests a possible environmental causative factor, perhaps more frequent in the rural environment, associated with PD. Men may be either more exposed to it or more susceptible to its effects than women.

Extrapyramidal signs in Alzheimer's disease

The occurrence and type of extrapyramidal signs were investigated in 143 patients with dementia of the Alzheimer type. Only 8% of the patients were free of extrapyramidal signs. The most common type of extrapyramidal involvement was a rigid, hypokinetic, and hypomimic pattern. Resting tremor was rarely encountered. Dyskinetic signs, mostly orofacial, were seen in 17%. These observations suggest that in most patients with advanced Alzheimers disease, there is a striatal dopaminergic hypofunction, appearing clinically as hypokinesia and rigidity. However, some patients exhibit predominantly dyskinetic signs, implying more complex basal ganglia dysfunction.

Atrial Fibrillation and Stroke Mortality and Causes of Death After the First Acute Ischemic Stroke

BACKGROUND AND PURPOSE Atrial fibrillation (AF) is a risk factor for stroke. This study was undertaken to determine the influence of AF on the mortality of stroke patients and on the causes of death after a stroke event. METHODS Patients with first ischemic stroke who were .35 to 74 years old and registered in the FINMONICA stroke register during 1982 through 1992 were analyzed (n = 6912). There were 642 patients with AF (9.3%) (mean age, 67 years) and 6270 patients without AF (90.3%) (mean age, 63 years). The association between AF and stroke mortality was investigated by use of logistic regression and Cox proportional hazards models. RESULTS Mortality was higher in the AF group both at 28 days (19.5% versus 14.4%, P < .001) and 1 year after the attack (30.5% versus 21.8%, P < .001). After adjustment for age and sex, the odds ratio for 28-day case fatality (AF versus non-AF) was 1.27 (95% CI, 1.03 to 1.56; P = .003), and that for 1-year mortality was 1.36 (95% CI, 1.14 to 1.63; P < .001). In the proportional hazards model, AF was a significant independent risk factor for 1-year mortality (hazard ratio, 1.26; 95% CI, 1.09 to 1.46; P = .002). Cardiac causes of death were more common in the AF group at the acute stage. In the course of 1 year, there were no differences in the distributions of causes of death. CONCLUSIONS Stroke patients with AF are at high risk of death both at the acute phase of stroke and during the subsequent year after the first acute stroke event. Mortality from cardiac diseases prevailed in the AF group during the acute phase of stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.

Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia.

Long‐term survival was examined for 218 patients with Alzheimers disease (AD) and 115 patients with multi‐infarct dementia (MID). The 14‐year survival rate for AD was 2.4% versus an expected rate of 16.6%, and for MID 1.7% versus 13.3% expected. MID showed a more malignant natural course than AD. Men carried a less favourable survival prognosis than women, both in AD and MID: the relative risk of dying for women was half that for men in both diseases. In MID, advanced disability indicated a relative risk of dying over twice as high. In both diseases the risk of death was substantially higher in the event of occurrence of primitive reflexes.