clinicaltrials.gov Identifier: NCT01829581.

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In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.

Objective:The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus.Methods: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. Results:The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects.Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p ϭ 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p ϭ 0.08). The VDADL score decreased from 6.00 to 1.50 (p ϭ 0.02). 4AP was well-tolerated.Conclusions: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. Level of evidence:This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias. Neurology Episodic ataxia type 2 (EA2) is a rare autosomal dominant hereditary disorder caused by heterozygous mutations of the gene CACNA1A on chromosome 19p13.1 The carbonic anhydrase inhibitor acetazolamide has been the drug of first choice for the preventive treatment of episodic ataxia (EA) and especially EA2 (doses of 250 -1,000 mg/day), 2,3 because of the serendipitous discovery of its dramatic impact. 4 Its efficacy, however, has never been proven in a randomized controlled trial. 5,6 Acetazolamide effectively prevents or attenuates the attacks in approximately 50%-75% of all patients with EA2. 7 Clinical experience, however, shows that many patients stop this treatment in the long run because they develop adverse effects or are no longer responsive. 5,6 Furthermore, the adverse effects of acetazolamide (such as nephrocalcinosis, hyperhidrosis, paresthesia, muscle stiffening with easy fatigability, and gastrointestinal disturbances) limit its usage. 6 In view of the need to identify an alternative treatment option to acetazolamide and on the basis of pilot studies in subjects with downbeat nystagmus 8 and EA 9 as well as findings from animal studies, 10,11 we conducted a prospective randomized, doubleblind, placebo-controlled crossover study of 4AP in familial EA with nystagmus (the majority

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IMPORTANCEThe association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. OBJECTIVE To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.DESIGN, SETTING, AND PARTICIPANTS Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).EXPOSURE Surgical hematoma evacuation vs conservative treatment. MAIN OUTCOMES AND MEASURESThe primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS,(4)(5)(6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. RESULTS Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm 3 vs 18.8 cm 3 ). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], −3.7% [95% CI, −8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm 3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume Յ12 cm 3 , 30.6% vs 62.3% [P = .003]; ARD, −34.7% [−38.8% to −30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume Ն15 cm 3 , 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).CONCLUSIONS AND RELEVANCE Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

Background and Purpose: Non-arteritic branch/central retinal artery occlusions (BRAO/CRAO) and amaurosis fugax (AF) are predominantly caused by embolism. Additionally, transported embolic material could cause ischemic stroke. The aim of the study was to investigate the prevalence, pattern and underlying cause of concurrent acute brain infarctions in unselected patients with RAO and AF. Methods: A total of 213 consecutive patients with BRAO (20.7%), CRAO (47.4%), or AF (31.9%) were retrospectively studied from 2008 to 2013. Magnetic resonance imaging (MRI) was used to detect acute brain infarctions and a cardiovascular workup was performed to detect underlying etiologies according to the Trial of Org 10172 in Acute Stroke Management (TOAST). Results: MRI was obtained after 23.78 (±32.26) hours from the time of symptom onset. Acute brain infarctions were detected in 49 patients (23%); 44 of them (89.8%) did not experience any additional neurological symptoms. Older age (p < 0.001/p < 0.001), hypertension (p = 0.01/p = 0.03), atrial fibrillation (p = 0.006/p = 0.03) and type of RAO (p = 0.02/p = 0.016) were associated with total/silent stroke, respectively. In multivariate analysis, only age and type of occlusion remained positive predictors for silent stroke. Etiology of BRAO/CRAO and AF remained undetermined in 124 patients (58.2%). This rate was lower in patients with acute stroke (40.8 vs. 63.4%). Conclusions: Silent brain infarction is a frequent finding in unselected patients with BRAO/CRAO and AF. Etiology remains undetermined in approximately every second case. Because silent brain infarctions bear a high risk of future stroke, patients with BRAO/CRAO and AF should undergo prompt neuroimaging and cardiovascular checkup, preferably on a stroke unit.

AimsEvidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.Methods and resultsWe pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67–35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33–21.37; P < 0.01). The hazard for the composite—balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10–5.70; P = 0.03).ConclusionRestarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing—between least risks for thromboembolic and haemorrhagic complications—provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.