[Analysis of direct costs in therapy of Parkinson disease]. / Analyse der direkten Kosten in der Parkinson-Therapie.

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.

High frequency stimulation of the basal ganglia for the treatment of movement disorders: current status and clinical results.

High frequency stimulation of the basal ganglia has gained much interest during the last years. Based on the reevaluation of the results of functional neurosurgery for movement disorders from Leksell's group, pallidotomy as lesional procedure was the first functional operation that underwent a renaissance for the treatment of movement disorders. The work by Benabid and Siegfried who carried out thalamic high frequency stimulation to suppress tremor, the knowledge about deep brain stimulation (DBS) for the treatment of chronic pain as well as better understanding in basal ganglia physiology and the development of reliable stimulation hardware led to an increasing number of centers worldwide who currently apply high frequency DBS for different movement disorders. In the present review the current status of DBS for movement disorders is presented and the results with high frequency stimulation targeted at different brain areas are summarized.

Deep-brain stimulation for Parkinson's disease.

Deep brain simulation (DBS) is a powerful new therapeutic approach for patients with Parkinson's disease. However, patient selection is critical for a valuable therapeutic result. Dopa sensitivity of the target symptoms, severe disability and low neurosurgical risks are among the major criteria for this indication. Other criteria like age or cognition must still be addressed in future prospective studies. The preferred target for DBS in PD is the subthalamic nucleus for various good reasons. However, prospective studies for this procedure are lacking and some clinical problems may be more easily solved with targeting the internal pallidum or the thalamus. Despite major progress in this field, much work remains to be done.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Pallidal stimulation for generalized dystonia. Report of three cases.

Pallidal stereotactic surgery is a well-accepted treatment alternative for Parkinson's disease. Another indication for this procedure is medically refractory dystonia, especially generalized dystonia with abnormal axial and extremity movements and postures. Improvement of dystonia after pallidotomy has been reported in several recent papers. In this report the authors describe three patients with generalized dystonia (two primary, one secondary) and their improvement after bilateral pallidal stimulation at follow-up times of between 6 and 18 months.

Is the medial globus pallidus a site for stimulation or lesioning in the treatment of Parkinson's disease?

After the encouraging report on bilateral pallidal stimulation by Siegfried in 1994, we started this procedure in 1995 and will report our experience in 6 patients with a mean follow-up of 1 year. In contrast to the good results of pallidotomy reported in the literature improving the 'on' symptoms as dyskinesias as well as 'off' symptoms such as rigidity, bradykinesia and on-off fluctuations, our results indicate that pallidal stimulation improves the 'off' symptoms only to a minor extent and L-dopa-induced dyskinesias remain the main indication. Considering the overall functional outcome, the question arises whether the medial globus pallidus should be lesioned or stimulated.

Liver damage, voluntary alcohol intake and brain histamine.

Liver dysfunction induced by protocaval anastomosis (PCA) in the rat is associated with a great reduction of hepatic alcohol and aldehyde dehydrogenase activities. Despite this, PCA rats voluntarily drank more alcohol than unoperated rats. When subjected to forced alcohol consumption, shunted rats maintained their exaggerated voluntary alcohol intake whereas unoperated rats developed aversion to alcohol. Hypothalamic levels of both histamine and histidine were very high in PCA rats. When these rats were chronically exposed to alcohol, there was a slight decrease in hypothalamic histidine concentration and consequently a lower histamine content. Chronic exposure to alcohol did not, however, influence hypothalamic tissue levels of histamine or histidine in unoperated rats. In both groups, chronic alcohol treatment exerted a stimulatory effect on hepatic alcohol metabolizing enzymes.

The intracerebroventricularly administered mast cells degranulator compound 48/80 increases the pituitary-adrenocortical activity in rats.

The effect of brain mast cells degranulation by compound 48/80 on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, and the involvement of a histaminergic mechanism in that stimulation was investigated in conscious rats. All the drugs were given intracerebroventricularly (icv), histamine antagonists 15 min prior to compound 48/80. Compound 48/80 induced a significant dose- and time-related increase in the serum corticosterone levels. That increase, measured 1 h after administration of compound 48/80, was moderately diminished by icv pretreatment of rats with mepyramine and cimetidine, histamine H1- and H2-receptor antagonists. Three hours after administration of compound 48/80 mast cells of the thalamus and the hypothalamus were completely degranulated. At the same time the thalamus and the whole brain histamine levels were substantially higher than in the saline-treated control rats. The above results suggest that histamine liberated from the brain mast cells and central histamine receptors play a moderate role in increasing the pituitary-adrenocortical activity by compound 48/80.

Brain histamine in rats with hepatic encephalopathy.

Chronic liver failure induced by portocaval anastomosis (PCA) in Wistar rats resulted in a dramatic increase in histamine concentration in hypothalamus and a smaller, but clearly pronounced, elevation in the rest of brain. Between 10 and 120 days following surgery, shunted rats exhibited a histamine level 2.4- to 13-fold higher in hypothalamus and 1.5- to 2.5-fold higher in the rest of brain as compared to their control, sham-operated pairs. There were no significant changes in histamine concentration in the other examined tissues. The increase in brain histamine could not be attributed to the inhibition of its degradation, because activity of histamine N-methyltransferase remained unchanged for at least 40 days. Although the activity of histidine decarboxylase also remained unchanged when measured at a saturating concentration of L-histidine, the increase in histamine content in brain seems to be due to its enhanced synthesis brought about by increased availability of L-histidine in the tissue, as indicated by two to four times higher concentrations of this amino acid in PCA rats.

Mucosal mono- and polyamine oxidase activities in digestive tract are distributed complementary to diamine oxidase.

The distribution of mucosal monoamine and polyamine oxidases along rat gastrointestinal tract presents a complementary pattern to that of diamine oxidase. The maximal diamine oxidase values are found in the last two thirds of small intestine, whereas the highest activities of monoamine and polyamine oxidase occur in the proximal duodenum and in the large intestine.