Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Low-frequency rTMS of the premotor cortex reduces complex movement patterns in a patient with pantothenate kinase-associated neurodegenerative disease (PKAN).

INTRODUCTION: Pantothenate kinase-associated neurodegenerative disease (PKAN) is a secondary generalized dystonia associated with an accumulation of iron in the basal ganglia and increased motor cortex excitability. A pilot study in three patients with secondary generalized dystonia had reported a reduced frequency of painful axial spasms following inhibitory 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the premotor cortex. PATIENT AND METHODS: We compared the effects of real versus sham rTMS on the frequency of the complex movement pattern and the need for additional benzodiazepine medication in a 6-year-old male patient with PKAN. A 20-minute session of left premotor 1-Hz rTMS was performed daily on 5 consecutive days. RESULTS: The occurrence of the complex movement pattern was gradually reduced from three to two attacks daily to one attack daily by real rTMS while sham rTMS had no effect. This reduction was obtained concomitantly with a similar reduction of additional benzodiazepines for both real and sham rTMS sessions. CONCLUSION: Inhibitory rTMS of the premotor cortex may be used to temporarily control motor symptoms in PKAN.

Effect of dietary mannan oligosaccharides and(or) pharmacological additions of copper sulfate on growth performance and immunocompetence of weanling and growing/finishing pigs.

Two experiments were conducted to determine the efficacy of mannan oligosaccharides (MOS) fed at two levels of Cu on growth and feed efficiency of weanling and growing-finishing pigs, as well as the effect on the immunocompetence of weanling pigs. In Exp. 1, 216 barrows (6 kg of BW and 18 d of age) were penned in groups of six (9 pens/treatment). Dietary treatments were arranged as a 2 x 2 factorial consisting of two levels of Cu (basal level or 175 ppm supplemental Cu) with and without MOS (0.2%). Diets were fed from d 0 to 38 after weaning. Blood samples were obtained to determine lymphocyte proliferation in vitro. From d 0 to 10, ADG, ADFI, and gain:feed (G:F) increased when MOS was added to diets containing the basal level of Cu, but decreased when MOS was added to diets containing 175 ppm supplemental Cu (interaction, P < 0.01, P < 0.10, and P < 0.05, respectively). Pigs fed diets containing 175 ppm Cu from d 10 to 24 and d 24 to 38 had greater (P < 0.05) ADG and ADFI than those fed the basal level of Cu regardless of MOS addition. Pigs fed diets containing MOS from d 24 to 38 had greater ADG (P < 0.05) and G:F (P < 0.10) than those fed diets devoid of MOS. Lymphocyte proliferation was not altered by dietary treatment. In Exp. 2, 144 pigs were divided into six pigs/pen (six pens/treatment). Dietary treatments were fed throughout the starter (20 to 32 kg BW), grower (32 to 68 kg BW), and finisher (68 to 106 kg BW) phases. Diets consisted of two levels of Cu (basal level or basal diet + 175 ppm in starter and grower diets and 125 ppm in finisher diets) with and without MOS (0.2% in starter, 0.1% in grower, and 0.05% in finisher). Pigs fed supplemental Cu had greater (P < 0.05) ADG and G:F during the starter and grower phases compared to pigs fed the basal level of Cu. During the finisher phase, ADG increased when pigs were fed MOS in diets containing the basal level of Cu, but decreased when MOS was added to diets supplemented with 125 ppm Cu (interaction, P < 0.05). Results from this study indicate the response of weanling pigs fed MOS in phase 1 varied with level of dietary Cu. However, in phase 2 and phase 3, diets containing either MOS or 175 ppm Cu resulted in improved performance. Pharmacological Cu addition improved gain and efficiency during the starter and grower phases in growing-finishing pigs, while ADG response to the addition of MOS during the finisher phase seems to be dependent upon the level of Cu supplementation.

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinson's disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. METHODS: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinson's disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. RESULTS: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US dollars 20,810, EURO 20,410, GB pounds 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7+/-21.8 (US dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Malignant transformation of benign gliomas during interstitial irradiation.

Interstitial curietherapy with 125-Iodine is an effective therapeutic option in the treatment of low grade gliomas. Four cases with astrocytoma grade II are presented, where tumour growth characteristics have changed to anaplasia during interstitial irradiation after a primary period of tumour regression. Anaplastic transformation could be due to a radiation effect or an insufficient therapeutic influence of interstitial irradiation on natural tumour progression of glioma growth due to genetic events.