M. Kloss

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.).

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.

OBJECTIVE: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. METHODS: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). RESULTS: Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09-2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56-1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01-1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27-0.48]) or had cerebral ischemia (OR = 0.32 [0.21-0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12-1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13-2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42-0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32-6.88]), but this was no longer significant after adjusting for baseline NIHSS score. CONCLUSION: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

OBJECTIVE: Several small to medium-sized studies indicated a link between cervical artery dissection (CeAD) and migraine. Migrainous CeAD patients were suggested to have different clinical characteristics compared to nonmigraine CeAD patients. We tested these hypotheses in the large Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) population. METHODS: A total of 968 CeAD patients and 653 patients with an ischemic stroke of a cause other than CeAD (non-CeAD IS) were recruited. CeAD patients with stroke (CeAD(stroke), n = 635) were compared with non-CeAD IS patients regarding migraine, clinical characteristics, and outcome. CeAD patients with and without migraine were compared in terms of clinical characteristics and outcome. RESULTS: Migraine was more common among CeAD(stroke) patients compared to non-CeAD IS patients (35.7 vs 27.4%, p = 0.003). The difference was mainly due to migraine without aura (20.2 vs 11.2%, p < 0.001). There were no differences in prevalence of strokes, arterial distribution, or other clinical or prognostic features between migrainous and nonmigrainous CeAD patients. CONCLUSION: Migraine without aura is more common among CeAD(stroke) patients compared to non-CeAD IS patients. The mechanisms and possible causative link remain to be proved. Although CeAD is often complicated by stroke, our data do not support increased risk of stroke in migrainous CeAD patients.