Derivation of Power M-Mode Transcranial Doppler Criteria for Angiographic Proven MCA Occlusion

BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing occlusion are needed for more reliable TCD performance at bedside in the acute stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we performed TCD examination for patients with symptoms of cerebral ischemia who underwent digital subtraction angiography (DSA). We used a standard insonation protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices (PI), and power M-mode resistance signature (absent, high, or low) in symptomatic middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral (i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA, aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings were evaluated with a receiver-operating characteristic (ROC) analysis for angiographically proven MCA occlusion. RESULTS: We studied 120 patients with acute cerebral ischemia with PMD-TCD examinations prior to or immediately after DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055). The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51). High resistance or absent M-mode flow signatures in the proximal MCA were present in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low-resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode signatures are highly predictive of a negative angiogram for MCA occlusion. CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA occlusion have been developed based on combination of MFV ratios and M-mode flow resistance signatures. Validation of these criteria will require multicenter studies.     

Extravasating Contrast Material on Angiography Following Carotid Angioplasty and Stenting: Not Necessarily Subarachnoid Hemorrhage

We describe a case of asymptomatic extravasation of iodinated contrast material into the sulci on digital subtraction angiography following carotid angioplasty and stenting resulting in sulcal hyperdensity on computed tomography (CT). We believe the mechanism for this observation is hyperperfusion injury and that in the absence of any associated clinical signs, it should not be considered alarming for subarachnoid hemorrhage.     

Trial of dextromethorphan/quinidine to treat levodopa‐induced dyskinesia in Parkinson's disease

Background : Nondopaminergic pathways represent potential targets to treat levodopa‐induced dyskinesia in Parkinson's disease (PD). This pilot‐study (NCT01767129) examined the safety/efficacy of the sigma‐1 receptor‐agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa‐induced dyskinesia. Methods : PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2‐week double‐blind, crossover treatment periods, with intervening 2‐week washout. After 14 days, a 2‐hour intravenous levodopa‐infusion was administered. Patient examinations were videotaped before infusion (“off” state) and every 30 minutes during and afterwards until patients returned to “off.” The primary endpoint was dyskinesia‐severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area‐under‐curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical‐change, and adverse‐events. Results : A total of 13 patients were randomized and completed the study (efficacy‐evaluable population). Dyskinesia‐severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area‐under‐curve 966.5 vs 1048.8; P = .191 [efficacy‐evaluable patients]), and significantly lower in a post‐hoc sensitivity analysis of the per‐protocol‐population (efficacy‐evaluable patients with ≥ 80% study‐drug‐compliance, n = 12) when measured from infusion start to 4‐hours post–infusion completion (area‐under‐curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion‐start to return to “off” (13.3 vs 14.9; P = .018 [efficacy‐evaluable patients]). A total of 9 patients rated dyskinesia “much/very much improved” on dextromethorphan/quinidine versus 1‐patient on placebo. Dextromethorphan/quinidine did not worsen PD‐motor scores, was generally well tolerated, and was associated with more frequent adverse events. Conclusion : This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa‐induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society     

Proportion of Patients With Hypertension Resolution Following Adrenalectomy for Primary Aldosteronism: A Systematic Review and Meta‐Analysis

Unilateral primary aldosteronism (PA) is often treated with adrenalectomy, but hypertension resolution rates are variable. A valid estimate of the postoperative normotension rate is necessary to inform the utility of PA testing and treatment. The authors searched MEDLINE In‐Process & Other Non‐Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials. Prospective adult cohort studies with surgically treated PA that reported resolution of hypertension without the aid of medications were included. Among 2620 abstracts identified by the search, 25 studies in the systematic review with data on 1685 patients were investigated. The pooled proportion of normotension following adrenalectomy was 52% (95% confidence interval, 0.44–0.60). Meta‐regression demonstrated a significant negative association between length of follow‐up and proportion of normotension, with normotension dropping by 6.7% per year of follow‐up (coefficient −0.006; 95% confidence interval, −0.01 to 0.002). Overall, approximately half of the patients experienced hypertension resolution, although this outcome may not be durable in all patients.

Primary aldosteronism (PA) is defined as a form of drug‐resistant and potentially curable hypertension with evidence of excess aldosterone secretion, suppressed plasma renin activity, and often hypokalemia.¹ Initially thought to be rare, PA is the leading cause of secondary hypertension. With increased screening and detection, the incidence of PA among hypertensive patients is currently reported at approximately 10%.² This syndrome has multiple etiologies, including inherited gene mutations,³ development of autoantibodies,⁴ and ectopic aberrant functional adrenal receptors.⁵ The clinical management is guided by the definition of unilateral vs bilateral adrenal involvement. With rare exception, adrenalectomy is reserved for unilateral adrenal disease.The proportion “cured” following adrenalectomy for patients with PA has been reported to range from 0% to 100%.⁶ However, “cure” is variably defined in the literature. These definitions include normal blood pressure (BP), normal BP without aid of antihypertensive medications, a reduced need for antihypertensive medications, and biochemical normalization, among others. Biochemical normalization of the aldosterone‐renin ratio is likely a necessary part of a definition of “cure.” At this time, however, there is no global consensus on the interpretation of postoperative aldosterone‐renin ratios with the existence of variable assays and cutoffs for even initial diagnosis. Therefore, from the patient''s perspective and in the absence of patient‐level clinical end point data, attainment of medication‐free normotension may be the most uniform and recognizable health benefit of surgical PA treatment. Individually reported results of long‐term resolution of hypertension without antihypertensive medications are between 30% and 70% following adrenalectomy.⁷ The primary aim of this systematic review and meta‐analysis was to determine the proportion of hypertension resolution without the aid of antihypertensive agents following adrenalectomy in patients with PA. To our knowledge, no previous meta‐analysis has been performed. A secondary objective was to identify patient‐level factors reported to be associated with hypertension resolution in patients managed with adrenalectomy.