To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with 'off' FOG. Nineteen patients (12 men, mean age 62.0 +/- 8.4 years) with Parkinson's disease and clinically significant FOG during 'off' states were videotaped whilst walking 130 m during 'off' and 'on' states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra-class correlation coefficient assessed inter-observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During 'off' states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during 'on' states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during 'on' states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of 'off'-related FOG.

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Patients with Parkinson's disease (PD) often experience freezing of gait, a debilitating phenomenon during which the subject suddenly becomes unable to start walking or to continue to move forward. Little is known about the gait of those subjects with PD who experience freezing of gait or the pathophysiology of freezing. One possibility is that freezing of gait is a truly paroxysmal phenomenon and that the usual walking pattern of subjects who experience freezing of gait is not different than that of other patients with PD who do not experience these transient episodes of freezing of gait. On the other hand, a recent study noted gait changes just prior to freezing and concluded that dyscontrol of the cadence of walking contributes to freezing. To address this question, we compared the gait of PD subjects with freezing of gait to PD subjects without freezing of gait. Given the potential importance of the dyscontrol of the cadence of walking in freezing, we focused on two aspects of gait dynamics: the average stride time (the inverse of cadence, a measure of the walking pace or rate) and the variability of the stride time (a measure of "dyscontrol," arrhythmicity and unsteadiness). We found that although the average stride time was similar in subjects with and without freezing, stride-to-stride variability was markedly increased among PD subjects with freezing of gait compared to those without freezing of gait, both while "on" (P<0.020) and "off" (P<0.002) anti-parkinsonian medications. Further, we found that increased gait variability was not related to other measures of motor control (while off medications) and levodopa apparently reduced gait variability, both in subjects with and without freezing. These results suggest that a paradigm shift should take place in our view of freezing of gait. PD subjects with freezing of gait have a continuous gait disturbance: the ability to regulate the stride-to-stride variations in gait timing and maintain a stable walking rhythm is markedly impaired in subjects with freezing of gait. In addition, these findings suggest that the inability to control cadence might play an important role in this debilitating phenomenon and highlight the key role of dopamine-mediated pathways in the stride-to-stride regulation of walking.

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Background and Purpose— If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods— Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results— Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results. Conclusions— In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.

BackgroundPerforming mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based.ObjectiveTo compare patients’ outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT.MethodsIn the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms.ResultsMT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 – 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 – 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO.ConclusionsIn selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR.Trial registration numberNCT03496064

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