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A K Granérus

Publications and source records attributed to A K Granérus.

At least 19 recordsLinked to original sources

[Drug treatment is beneficial also for elderly patients with Parkinson disease. Important to consider also other co-existing diseases].

Parkinson's disease is a relatively common disorder in elderly patients. With carefully performed treatment a considerable improvement can be seen also in patients of high age. L-dopa as well as other antiparkinsonian drugs should be used in lower doses than those subscribed for younger patients. Cognitive decline implies a certain risk for mental confusion, in which case the dose of the causing agent has to be lowered or the treatment interrupted.

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Both total and phosphorylated tau are increased in Alzheimer's disease.

BACKGROUND: [corrected] Pathological tau protein concentrations in CSF are found in both Alzheimer's disease (AD) and frontotemporal dementia (FTD), but studies on brain tissue have suggested that the tau pathology in AD differs from that in FTD and that the difference may be related to the degree of phosphorylation. As CSF tau protein is increased after stroke, tau may also be implicated in the pathophysiology of vascular dementia, of which subcortical arteriosclerotic encephalopathy (SAE) is a putative subtype. OBJECTIVES: To investigate the nature of tau protein in CSF and the involvement of total CSF tau and phosphorylated CSF tau (phosphotau) in various types of dementia. METHODS: Using ELISAs for total tau and tau phosphorylated at Thr181 (phosphotau), the CSF concentrations of total tau and phosphotau were determined in patients with probable and possible AD (n=41 and 19, respectively), FTD (n=18), SAE (n=17), and Parkinson's disease (PD; n=15) and in age matched controls (n=17). All the antibodies stained the lower molecular weight bands, whereas only the antibodies that recognise phosphorylated tau stained the higher molecular bands. RESULTS: Both CSF tau and CSF phosphotau were increased in probable AD compared with FTD (p<0.001), SAE (p<0.001), PD (p<0.001), and controls (p<0.001). CSF phosphotau was increased in possible AD compared with FTD (p<0.001) and SAE (p<0.001). CSF tau and CSF phosphotau were positively correlated in all the groups. Molecular weight forms of tau ranging from 25 kDa to 80 kDa were found in the CSF CONCLUSION: Both phosphorylated and unphosphorylated tau isoforms were present in the CSF, and tau protein appeared in both truncated and full length forms. The results suggest that the CSF concentrations of tau and phosphotau are increased in about two thirds of patients with probable AD and in half of those with possible AD but are normal in FTD, SAE, and PD compared with normal aging. Values in the normal range do not exclude AD.

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ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT.

Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2beta-carboxymethyl-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was performed with six PD patients in whom the [123I]beta-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomatology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [123I]beta-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

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Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden.

PURPOSE AND METHODS: To investigate the possible impact of nutritional and environmental risk factors for idiopathic Parkinson's disease (IP), a case-control study was performed in the county of Ostergötland in southeastern Sweden. The study involved 113 cases of IP and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire. RESULTS: No increased risk was found for any of the nutritional items in which information was requested. A reduced risk was found for coffee, wine, and liquor at various consumption levels but also for fried or broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. All these food and drink items contain niacin. As in many studies, the frequency of preceding and present smoking was reduced in IP patients. Various occupational groups and exposures were analyzed and increased risks of IP in men were found for agricultural work along with pesticide exposure; this was also the case for male carpenters and female cleaners. CONCLUSIONS: The findings indicate that nutritional factors and occupational exposures, especially to pesticides, could be of etiologic importance in IP.

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Maintenance ECT in Parkinson's disease.

Electroconvulsive therapy (ECT) has an anti-Parkinsonian effect. In two cases repeated single ECT, i.e. maintenance ECT (MECT), caused different, hitherto unreported positive effects. One patient had either severe mental side effects from higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT entailed a marked improvement in parkinsonian symptoms without mental side effects. Another patient with depression as well as Parkinson's disease who showed a slight improvement of motor symptoms after a series of ECT presented further anti-parkinsonian effects on MECT.

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L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma.

OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients. METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time. RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy. CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.

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Age-standardized incidence and prevalence of Parkinson's disease in a Swedish community.

Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low L-dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

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ECT in Parkinson's disease. Changes in motor symptoms, monoamine metabolites and neuropeptides.

Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.

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Influence of Parkinson's disease on oral health.

Thirty patients with Parkinson's disease were investigated with regard to their oral health. They had significantly more teeth and less caries than a control group of corresponding age. However, the salivary secretion rate was significantly lower with advancing parkinsonian symptoms. It is concluded that not only motor impairment but also autonomic dysfunction, as an expression of a more advanced neuron degeneration, could be of importance when the possibility of maintaining a good oral health in parkinsonian patients is considered.

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'On-off' phenomenon in Parkinson's disease: relationship between dopa and other large neutral amino acids in plasma.

Administration of a low-protein diet to parkinsonian patients with "on-off" syndromes consistently increased the total daily time of "on" states when compared with a high-protein diet. The clinical effect of the low-protein diet may be due to a marked decrease in the plasma concentration of large neutral amino acids that compete with L-dopa for carrier-mediated transport into the brain.

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A double-blind evaluation of electroconvulsive therapy in Parkinson's disease with "on-off" phenomena.

Eleven patients with severe Parkinson's disease and on-off-phenomena were included in a controlled double-blind study on the effect of electroconvulsive therapy (ECT). Pharmacological treatment was optimally adjusted before the trial. The severity of extrapyramidal symptoms was measured before, during and after the treatment. The patients were randomly allocated into one group, receiving active ECT and another, receiving sham treatment. The patients given active ECT showed significantly (P less than 0.05) prolonged duration of "on"-phases after ECT, in comparison to the sham-treated group. When collecting data from the controlled part of the study and the subsequent with open administration of ECT, the treatment was in addition found to significantly decrease the time and number of steps required to walk 10 meters. Moreover it reduced the severity of parkinsonian symptoms according to the Webster scale. The improvement induced by ECT was generally short-lasting. Lumbar punctures were performed before and after ECT. The concentrations of monoamine metabolites in cerebrospinal fluid were not affected by the treatment. The results indicate that ECT has an antiparkinsonian effect which probably is mediated via changed responsiveness of dopamine receptors and that further improvement is possible in patients, therapy resistant to the presently available medication.

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"On-off" phenomenon in Parkinson's disease: correlation to the concentration of dopa in plasma.

To investigate the relation between "on-off" fluctuations in symptomatology and bioavailability of dopa in patients with Parkinson's disease, five Parkinsonian patients with pronounced "on-off" symptoms were studied. Continuously during the study the degree of disability in the patients was registered. Every one hour, and in addition, whenever there was a change from "on" to "off" or vice versa, a blood sample was collected for dopa determination. Since dopa is transported from plasma into the brain by a saturable carrier for which it has to compete with endogenous large neutral amino acids (LNAA), the concentrations of these competitors were measured too. In four of the patients there were considerable oscillations in the plasma dopa concentration during the day; in one of these patients the highest value was as much as 12 times higher than the lowest value. These dramatic fluctuations in the absolute concentration of dopa in plasma had a major influence on the relative dopa concentrations (calculated as the ratio dopa/sum of LNAA) as the fluctuations in the concentrations of LNAA in plasma were much less pronounced. Consequently, the absolute and the relative concentrations of dopa in plasma were highly parallelled. In four of the five patients "on"-periods began within one hour after a peak in the concentration of dopa in plasma and in the fifth patient five out of seven "on"-periods were preceded by a rise in plasma dopa concentration within the same time interval. From the present data it could be concluded that the "on-off" phenomenon in Parkinson's disease, at least partly, is due to oscillations in the concentration of dopa in plasma. A reduction in the variations of the concentration of dopa in plasma seems to be necessary to overcome the "on-off" problem. The introduction of a slow release preparation of dopa is therefore urgently warranted. The concentration of LNAA in plasma must, however, also be considered in this context.

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Neuroendocrine evidence for increased responsiveness of dopamine receptors in humans following electroconvulsive therapy.

The previous finding that electroconvulsive therapy (ECT) enhances effects of dopamine (DA) agonists was further investigated in the present clinical experiment using neuroendocrine techniques. Apomorphine chloride (AP) (0.18-0.24 mg IV) induced stimulation of growth hormone (GH) and suppression of prolactin (PRL), as shown 2-3 days before and after ECT in mentally depressed patients (N = 12) and therapy-resistant parkinsonian patients with on-off phenomena (N = 9). AP-stimulated GH secretion was not significantly affected by ECT, whereas AP-induced suppression of PRL, expressed as percentage of baseline PRL levels, was significantly enhanced after ECT. Changes in clinical and hormonal parameters were not significantly correlated. Control patients not receiving ECT showed no significant changes in AP-induced GH secretion or PRL suppression in repeated investigations. The results support the view that ECT increases responsiveness of DA receptors and indicates that AP-induced suppression of PRL is a useful model to reflect these changes in humans.

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Predictors for improvement after electroconvulsive therapy in parkinsonian patients with on-off symptoms.

The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in nine parkinsonian patients with "on-off" phenomena. The patients were maintained on previously adjusted doses of antiparkinsonian drugs during and after ECT. Parkinsonian as well as mental symptoms were rated before and after treatment. Basal serum levels of prolactin (PRL) and growth hormone (GH) as well as apomorphine induced changes (0.24 mg i.v.) in these levels were investigated three days before start of treatment. Marked improvement of parkinsonian symptoms was seen in five patients. Two further patients showed slight improvements. The improvement persisted for 2-41 weeks. Improvement after ECT was found to correlate with age at the time of treatment and with duration of L-dopa therapy as well as the estimated life-dose of L-dopa. No correlation was found between depression before treatment, basal serum levels of GH and PRL or apomorphine induced changes in these hormone levels. The investigation indicates that ECT is a valuable adjuvant in the treatment of a selected group of parkinsonian patients with "on-off" phenomena. Furthermore, the results support our earlier proposal that ECT increases the responsiveness in postsynaptic dopamine sensitive structures.

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