Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND: The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS: An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS: In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS: Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION: BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS).

Cost-Effectiveness Analysis of Etranacogene Dezaparvovec Versus Extended Half-Life Prophylaxis for Moderate-to-Severe Haemophilia B in Germany.

BACKGROUND AND OBJECTIVE: Haemophilia B is a rare genetic disease that is caused by a deficiency of coagulation factor IX (FIX) in the blood and leads to internal and external bleeding. Under the current standard of care, haemophilia is treated either prophylactically or on-demand via intravenous infusions of FIX. These treatment strategies impose a high burden on patients and health care systems as haemophilia B requires lifelong treatment, and FIX is costly. Etranacogene dezaparvovec (ED) is a gene therapy for haemophilia B that has been recently approved by the United States Food and Drug Administration and has received a recommendation for conditional marketing authorization by the European Medicines Agency. We aimed to examine the cost-effectiveness of ED versus extended half-life FIX (EHL-FIX) prophylaxis for moderate-to-severe haemophilia B from a German health care payer perspective. METHODS: A microsimulation model was implemented in R. The model used data from the ED phase 3 clinical trial publication and further secondary data sources to simulate and compare patients receiving ED or EHL-FIX prophylaxis over a lifetime horizon, with the potential for ED patients to switch treatment to EHL-FIX prophylaxis when the effectiveness of ED waned. Primary outcomes of this analysis included discounted total costs, discounted quality-adjusted life years (QALYs), incremental cost-effectiveness, and the incremental net monetary benefit. The annual discount rate for costs and effects was 3%. Uncertainty was examined via probabilistic analysis and additional univariate sensitivity analyses. RESULTS: Probabilistic analysis indicated that patients treated with ED instead of EHL-FIX prophylaxis gained 0.50 QALYs and experienced cost savings of EUR 1,179,829 at a price of EUR 1,500,000 per ED treatment. ED was the dominant treatment strategy. At a willingness to pay of EUR 50,000/QALY, the incremental net monetary benefit amounted to EUR 1,204,840. DISCUSSION: Depending on the price, ED can save costs and improve health outcomes of haemophilia patients compared with EHL-FIX prophylaxis, making it a potentially cost-effective alternative. These results are uncertain due to a lack of evidence regarding the long-term effectiveness of ED.

Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland.

BACKGROUND: Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval. OBJECTIVES: This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype. METHODS: We developed a three-state Markov cohort model with a cycle length of 1 month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses. RESULTS: Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%. CONCLUSIONS: Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies.

Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland: a retrospective study using insurance claims data.

AIM OF THE STUDY: Newly approved therapies with high and uncertain budget impact pose challenges to public health care systems worldwide. One recent example is chimeric antigen receptor T cell (CAR-T) therapies for adults with large B-cell lymphoma (LBCL). This study's primary objective is to examine the expenditures of Swiss public payers before, during, and after CAR-T cell therapy in patients with LBCL aged ≥30 years. Its secondary objective is to analyse 24-month survival rates. METHODS: This retrospective observational data analysis used the administrative databases of the Swiss health insurers Concordia, CSS, Groupe Mutuel, Helsana, ÖKK, Sanitas, SWICA, Sympany, and Visana. These health insurers or groups provide mandatory health insurance to approximately 78% of Swiss residents in 2021. Using the relevant procedure codes, we identified CAR-T therapies administered between October 2018 (first approval) and June 2021 (treatment identification cut-off). Patients aged <30 years were excluded because they might be treated for pediatric acute lymphoblastic leukaemia. Expenditures were categorised as pre-infusion, peri-infusion (excluding CAR-T therapy acquisition costs), and post-infusion based on the time of service provision. Overall survival rates were estimated using the Kaplan-Meier method. RESULTS: This study identified 81 patients aged ≥30 years, with a median follow-up period for censored observations of 27 months (interquartile range: 21-31 months). The median age group was 70-74, and 60% of patients were male. Mean healthcare expenditures per patient per month amounted to CHF 8,115-22,564 pre-infusion, CHF 38,490 peri-infusion, and CHF 5,068-11,342 post-infusion. For the total peri- and post-infusion period (i.e. 1-month before infusion to 23 months after infusion), mean healthcare expenditures amounted to CHF 215,737. The 24-month overall survival rate was 48% (95% confidence interval: 38-61%). CONCLUSIONS: Healthcare expenditures after CAR-T cell infusion are relatively high compared to previous estimates of patients with LBCL in the last year of treatment. Further research is needed to understand the drivers behind these post-infusion expenditures. Especially, clinical data should be used to assess the time until disease progression. The analysis of 24-month overall survival is consistent with results from the pivotal trials. Our findings stress the importance of post-approval studies to monitor real-world expenditures and outcomes related to innovative therapies.

Endovascular therapy of 623 patients with anterior circulation stroke.

BACKGROUND AND PURPOSE: Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both. METHODS: We prospectively acquired data for 623 patients with acute cerebral infarcts in the carotid artery territory who received endovascular treatment at a single center. Logistic regression analysis was performed to determine predictors of outcome. RESULTS: Median National Institutes of Health Stroke Scale (NIHSS) at admission was 15. Partial or complete recanalization was achieved in 70.3% of patients; it was independently associated with hypercholesterolemia (P=0.02), absence of coronary artery disease (P=0.023), and more proximal occlusion site (P<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients reached favorable outcome (modified Rankin scale score 0-2). Good collaterals (P<0.0001), recanalization (P=0.023), hypercholesterolemia (P=0.03), lower NIHSS at admission (P=0.001), and younger age (P<0.0001) were independent predictors for survival. More peripheral occlusion site (P<0.0001), recanalization (P<0.0001), hypercholesterolemia (P=0.002), good collaterals (P=0.002), lower NIHSS (P<0.0001), younger age (P<0.0001), absence of diabetes (P=0.002), and no previous antithrombotic therapy (P=0.036) predicted favorable outcome. Time to treatment was only a predictor of outcome, when collaterals were excluded from the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was independently predicted by poor collaterals (P=0.004). CONCLUSIONS: Several independent predictors for outcome and complications were identified. Unlike in intravenous thrombolysis trials, time to treatment was a predictor of outcome only when collaterals were excluded from the model, indicating the important role of collaterals for the time window.

Impact of thrombolysis on stroke outcome at 12 months in a population: the Bern stroke project.

BACKGROUND AND PURPOSE: Thrombolysis improves outcome of patients with acute ischemic stroke, but it is unknown whether thrombolysis has a measurable effect on long-term outcome in a defined population. METHODS: We prospectively assessed demographic data, management, and outcome of acute ischemic stroke patients admitted within 48 hours to 18 primary care hospitals of the canton of Bern (969 299 inhabitants) during 12 months. Blinded follow-up was obtained at 3 and 12 months. Predictors of mortality and favorable outcome (modified Rankin Scale score ≤2) at 3 and 12 months using logistic regression were analyzed. RESULTS: From December 2007 to December 2008, 807 patients (mean age, 72 years) were included. Median National Institutes of Health Stroke Scale score on admission was 5; 107 patients (13%) received intravenous, intra-arterial, or mechanical thrombolysis. Estimated cumulative mortality at 3 months was 20.6% and at 12 months 27.4%. Age 75 years or older, higher National Institutes of Health Stroke Scale scores, and higher Charlson comorbidity index were independent predictors of mortality at 3 and 12 months. Estimated favorable outcome at 3 months was 48.2% and at 12 months was 44.6%. Thrombolysis was the only modifiable independent predictor of favorable outcome at 3 (relative risk, 1.49; 95% CI, 1.18-1.89) and 12 months (relative risk, 1.59; 95% CI, 1.24-2.04), whereas age younger than 75 years, male gender, National Institutes of Health Stroke Scale score <4, and lower Charlson comorbidity index were nonmodifiable predictors. CONCLUSIONS: Thirteen percent of acute ischemic stroke patients admitted within 48 hours to Bernese hospitals underwent thrombolysis, which exerted a measurable effect on 3-month outcome in this population. This effect was sustained at 12 months. Age, stroke severity, Charlson comorbidity index, and male gender were independent nonmodifiable predictors of outcome.

Clinical Reasoning: A Dizzy Architect.

There is an increasing body of evidence describing an association between anti-Kelch-like protein 11 (KLHL11) encephalitis and various tumors such as seminoma. However, when the diagnosis of neoplasia is uncertain and the clinical syndrome resembles those caused by other etiologies, the possibility of anti-KLHL11 encephalitis may not be obvious during early clinical evaluations. We present the case of a 68-year-old man with clinical features of anti-KLHL11 encephalitis, in whom no clear signs of an active neoplasia could be found. However, a burnt-out germ cell tumor was suspected. This case highlights the importance of having a high clinical suspicion for anti-KLHL11 encephalitis in patients who exhibit symptoms and signs, even in the absence of an active tumor.

Intracranial hemorrhage, outcome, and mortality after intra-arterial therapy for acute ischemic stroke in patients under oral anticoagulants.

BACKGROUND AND PURPOSE: Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7. The present study assessed the risk of symptomatic intracranial hemorrhage, clinical outcome, and mortality after intra-arterial therapy (IAT) in patients with and without previous use of OAC. METHODS: Consecutive patients treated with IAT from December 1992 to October 2010 were included. Clinical outcome and mortality were assessed 90 days after stroke onset. Patients with and without previous use of OAC were compared. RESULTS: Overall, 714 patients were treated with IAT. Twenty-eight patients (3.9%) were under OAC at time of symptom onset. Median INR in the OAC group was 1.79 (interquartile range [IQR], 1.41-2.3) and 1.01 (IQR, 1.0-1.09; P<0.0001) in the group without OAC. Patients treated with OAC at admission underwent more often mechanical-only IAT than did patients without OAC (46.4% versus 12.8%; P<0.0001). Comparing patients with and without previous use of OAC, we did not find any statistical difference in the rate of symptomatic intracranial hemorrhage (7.1% versus 6.0%; P=0.80), unfavorable outcome (modified Rankin Scale score, 3-6; 67.9% versus 50.9%; P=0.11), and mortality (17.9% versus 21.6%; P=0.58). CONCLUSIONS: Previous use of OAC did not significantly increase the risk of symptomatic intracranial hemorrhage after IAT or the risk of unfavorable outcome and mortality 90 days after IAT.

Decompressive craniectomy after intra-arterial thrombolysis: safety and outcome.

OBJECTIVES: Data on decompressive craniectomy (DC) after intra-arterial thrombolysis (IAT) for treatment of malignant middle cerebral artery (MCA) stroke are lacking. METHODS: The authors compared consecutive patients with middle cerebral artery (MCA) strokes who underwent decompressive craniectomy (DC) after IAT with DC patients without prior thrombolysis. RESULTS: Thirty of 2395 consecutive patients with acute ischaemic stroke or transient ischaemic attack were treated with DC because of space-occupying oedema 12-72 h after symptom onset. Fifteen patients underwent intra-arterial thrombolysis (IAT) prior to DC. Baseline characteristics did not differ between thrombolysed and non-thrombolysed patients except for lower National Institute of Health Stroke Scale score in non-thrombolysed patients (median National Institute of Health Stroke Scale 17 vs. 14, p=0.033). The outcome at 3 months was favourable (modified Rankin scale 0-3) in seven (47%) thrombolysed patients and in four (27%) non-thrombolysed patients (p=0.45). Mortality and major complications after DC did not differ between the two groups (p>0.05). Older age (p=0.037) and previous hypertension (p=0.047) independently predicted unfavourable outcome in DC patients, but not IAT prior DC. CONCLUSIONS: There was no difference of outcome of patients with DC with or without prior IAT. DC after IAT did not cause any more complications than DC without prior thrombolysis.

Outcome after thrombolysis for acute isolated posterior cerebral artery occlusion.

BACKGROUND: To date, there is limited data on intra-arterial thrombolysis (IAT) and intravenous thrombolysis (IVT) for isolated posterior cerebral artery (PCA) occlusion. We aimed to evaluate recanalization, outcome and quality of life in patients who undergo thrombolysis for isolated PCA occlusion. METHODS: Analysis of 9 patients treated with IAT and 9 patients treated with IVT with short-term (3 months) outcome and long-term (median 23 months) outcome after IAT. RESULTS: 9 of 546 patients treated with IAT (4 women and 5 men; median age 66 years) had isolated PCA occlusion. Median baseline National Institute of Health Stroke Scale (NIHSS) score on admission was 9. Eight patients presented with visual field defects and variable additional symptoms. One patient suffered bithalamic infarction. Median time to treatment was 5.8 h. Recanalization was complete in 2, partial in 2, minimal in 2, and not achieved in 3 patients. Recanalization tended to be better when the microcatheter was placed in or close to the thrombus. We observed no major complications, and 3 months outcome was favorable (modified Rankin Scale score 0-2) in 67% of the patients after IAT. During the same period, 9 patients with PCA occlusion were treated with IVT with 89% favorable clinical outcomes at 3 months. At long-term follow-up after IAT, neuropsychological domains were more severely impaired than other neurologic functions. CONCLUSION: IAT is a feasible treatment of isolated PCA strokes. Clinical outcome was favorable in the majority of patients after IAT and IVT. No major complications were observed. Further studies are needed to compare IAT and IVT for isolated PCA stroke.

Trunk sway in mildly disabled multiple sclerosis patients with and without balance impairment.

Multiple sclerosis (MS) causes a broad range of neurological symptoms. Most common is poor balance control. However, knowledge of deficient balance control in mildly affected MS patients who are complaining of balance impairment but have normal clinical balance tests (CBT) is limited. This knowledge might provide insights into the normal and pathophysiological mechanisms underlying stance and gait. We analysed differences in trunk sway between mildly disabled MS patients with and without subjective balance impairment (SBI), all with normal CBT. The sway was measured for a battery of stance and gait balance tests (static and dynamic posturography) and compared to that of age- and sex-matched healthy subjects. Eight of 21 patients (38%) with an Expanded Disability Status Scale of 1.0-3.0 complained of SBI during daily activities. For standing on both legs with eyes closed on a normal and on a foam surface, patients in the no SBI group showed significant differences in the range of trunk roll (lateral) sway angle and velocity, compared to normal persons. Patients in the SBI group had significantly greater lateral sway than the no SBI group, and sway was also greater than normal in the pitch (anterior-posterior) direction. Sway for one-legged stance on foam was also greater in the SBI group compared to the no SBI and normal groups. We found a specific laterally directed impairment of balance in all patients, consistent with a deficit in proprioceptive processing, which was greater in the SBI group than in the no SBI group. This finding most likely explains the subjective symptoms of imbalance in patients with MS with normal CBT.

D-dimers predict stroke subtype when assessed early.

BACKGROUND: Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations. METHODS: Levels of coagulation activation [fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT)] and fibrinolysis activation [plasmin-alpha(2)-antiplasmin complex (PAP), D-dimers] markers were measured in 98 consecutive patients with a first-ever acute ischemic stroke admitted within 12 h after symptom onset. RESULTS: Median age was 67 years and 44% were women. Median time from symptom onset to blood sampling was 4 h. Stroke subtype was classified as 'cardioembolic' (54%), 'large-artery atherosclerosis' (11%), 'small-vessel disease' (5%), 'other determined' (9%) or 'undetermined etiology' (20%). Patients with cardioembolic stroke suffered more often from coronary artery disease than patients with other stroke etiologies (40 vs. 22%, p = 0.019). There were no differences in age, sex, stroke severity, time to blood sampling, frequency of hypertension, diabetes mellitus or current smoking. D-dimers (medians) were higher in patients with cardioembolic strokes than in those with other etiologies (615 vs. 322 microg/l, p < 0.001). No differences in F1+2, FPA, TAT or PAP levels were found. After multivariate analysis, higher D-dimer levels remained independently associated with cardioembolic stroke (p = 0.022). When measured within 6 h, D-dimers below 300 microg/l excluded cardioembolic stroke with a sensitivity of 100% and a specificity of 52%. CONCLUSIONS: Low D-dimer levels in the first few hours make a cardioembolic stroke unlikely, and may be useful to guide further investigations. Other coagulation markers were not useful in differentiating between different stroke etiologies.

Effectiveness of AbobotulinumtoxinA in Post-stroke Upper Limb Spasticity in Relation to Timing of Treatment.

Background: Recent studies of botulinum toxin for post-stroke spasticity indicate potential benefits of early treatment (i. e., first 6 months) in terms of developing hypertonicity, pain and passive function limitations. This non-interventional, longitudinal study aimed to assess the impact of disease duration on the effectiveness of abobotulinumtoxinA treatment for upper limb spasticity. Methods: The early-BIRD study (NCT01840475) was conducted between February 2013 and 2018 in 43 centers across Germany, France, Austria, Netherlands and Switzerland. Adult patients with post-stroke upper limb spasticity undergoing routine abobotulinumtoxinA treatment were followed for up to four treatment cycles. Patients were categorized by time from stroke event to first botulinum toxin-A treatment in the study (as defined by the 1st and 3rd quartiles time distribution) into early-, medium- and late- start groups. We hypothesized that the early-start group would show a larger benefit (decrease) as assessed by the modified Ashworth scale (MAS, primary endpoint) on elbow plus wrist flexors compared with the late-start group. Results: Of the 303 patients enrolled, 292 (96.4%) received ≥1 treatment and 186 (61.4%) received 4 injection cycles and completed the study. Patients in all groups showed a reduction in MAS scores from baseline over the consecutive injection visits (i.e., at end of each cycle). Although reductions in MAS scores descriptively favored the early treatment group, the difference compared to the late group did not reach statistical significance at the last study visit (ANCOVA: difference in adjusted means of 0.15, p = 0.546). Conclusions: In this observational, routine-practice study, patients in all groups displayed a benefit from abobotulinumtoxinA treatment, supporting the effectiveness of treatment for patients at various disease stages. Although the data revealed some trends in favor of early vs. late treatment, we did not find strong evidence for a significant benefit of early vs. late start of treatment in terms of reduction in MAS scores.

Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: There are only limited data on whether prior statin use and/or cholesterol levels are associated with intracranial hemorrhage (ICH) and outcome after intra-arterial thrombolysis. The purpose of this study was to evaluate the association of statin pretreatment and cholesterol levels with the overall frequency of ICH, the frequency of symptomatic ICH, and clinical outcome at 3 months. METHODS: We analyzed 311 consecutive patients (mean age, 63 years; 43% women) who received intra-arterial thrombolysis. RESULTS: Statin pretreatment was present in 18%. The frequency of any ICH was 20.6% and of symptomatic ICH 4.8%. Patients with any ICH were more often taking statins (30% versus 15%, P=0.005), more often had atrial fibrillation (45% versus 30%, P=0.016), had more severe strokes (mean National Institute of Health Stroke Scale score 16.5 versus 14.7, P=0.022), and less often good collaterals (16% versus 24%, P=0.001). Patients with symptomatic ICH were more often taking statins (40% versus 15%, P=0.009) and had less often good collaterals (0% versus 24%, P<0.001). Any ICH or symptomatic ICH were not associated with cholesterol levels. After multivariate analysis, the frequency of any ICH remained independently associated with previous statin use (OR, 3.1; 95% CI, 1.53 to 6.39; P=0.004), atrial fibrillation (OR, 2.5; CI, 1.35 to 4.75; P=0.004), National Institutes of Health Stroke Scale score (OR, 1.1; CI, 1.00 to 1.10; P=0.037), and worse collaterals (OR, 1.7; CI, 1.19 to 2.42; P=0.004). There was no association of outcome with prior statin use, total cholesterol level, or low-density lipoprotein cholesterol level. CONCLUSIONS: Prior statin use, but not cholesterol levels on admission, is associated with a higher frequency of any ICH after intra-arterial thrombolysis without impact on outcome.

Stent placement in acute cerebral artery occlusion: use of a self-expandable intracranial stent for acute stroke treatment.

BACKGROUND AND PURPOSE: Stent placement has been applied in small case series as a rescue therapy in combination with different thrombolytic agents, percutaneous balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke treatment. These studies report a considerable mortality and a high rate of intracranial hemorrhages when balloon-mounted stents were used. This study was performed to evaluate feasibility, efficacy, and safety of intracranial artery recanalization for acute ischemic stroke using a self-expandable stent. METHODS: All patients treated with an intracranial stent for acute cerebral artery occlusion were included. Treatment comprised intraarterial thrombolysis, thromboaspiration, MT, PTA, and stent placement. Recanalization result was assessed by follow-up angiography immediately after stent placement. Complications related to the procedure and outcome at 3 months were assessed. RESULTS: Twelve patients (median NIHSS 14, mean age 63 years) were treated with intracranial stents for acute ischemic stroke. Occlusions were located in the posterior vertebrobasilar circulation (n=6) and in the anterior circulation (n=6). Stent placement was feasible in all procedures and resulted in partial or complete recanalization (TIMI 2/3) in 92%. No vessel perforations, subarachnoid, or symptomatic intracerebral hemorrhages occurred. One dissection was found after thromboaspiration and PTA. Three patients (25%) had a good outcome (mRS 0 to 2), 3 (25%) a moderate outcome (mRS 3), and 6 (50%) a poor outcome (mRS 4 to 6). Mortality was 33.3%. CONCLUSIONS: Intracranial placement of a self-expandable stent for acute ischemic stroke is feasible and seems to be safe to achieve sufficient recanalization.

Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation.

OBJECTIVE: To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms "off" and "on" levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality. RESULTS: Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery ("on" dopamine/"on" STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score). CONCLUSIONS: We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.

Cerebrospinal fluid outflow resistance as a diagnostic marker of spontaneous cerebrospinal fluid leakage.

OBJECTIVE Spinal CSF leakage causes spontaneous intracranial hypotension (SIH). The aim of this study was to characterize CSF dynamics via lumbar infusion testing in patients with and without proven spinal CSF leakage in order to explore possible discriminators for the presence of an open CSF leak. METHODS This analysis included all patients with suspected SIH who were treated at the authors' institution between January 2012 and February 2015. The gold standard for "proven" CSF leakage is considered to be extrathecal contrast accumulation after intrathecal contrast injection. To characterize CSF dynamics, the authors performed computerized lumbar infusion testing to measure lumbar pressure at baseline (opening pressure) and at plateau, as well as pulse amplitude, CSF outflow resistance (RCSF), craniospinal elastance, and pressure-volume index. RESULTS Thirty-one patients underwent clinical imaging and lumbar infusion testing and were included in the final analysis. A comparison of the 14 patients with proven CSF leakage with the 17 patients without leakage showed a statistically significantly lower lumbar opening pressure (p < 0.001), plateau pressure (p < 0.001), and RCSF (p < 0.001) in the group with leakage. Sensitivity, specificity, and positive and negative predictive values for an RCSF cutoff of ≤ 5 mm Hg/(ml/min) were 0.86, 1.0, 1.0, and 0.89 (area under the curve of 0.96), respectively. The median pressure-volume index was higher (p = 0.003), and baseline (p = 0.017) and plateau (p < 0.001) pulse amplitudes were lower in patients with a proven leak. CONCLUSIONS Lumbar infusion testing captures a distinct pattern of CSF dynamics associated with spinal CSF leakage. RCSF assessed by computerized lumbar infusion testing has an excellent diagnostic accuracy and is more accurate than evaluating the lumbar opening pressure. The authors suggest inclusion of RCSF in the diagnostic criteria for SIH.