Konark Malhotra

Imaging in Endovascular Stroke Trials

Ischemic stroke remains a leading cause of death and disability worldwide. Various endovascular trials have addressed clinical outcomes without elucidating the impact of imaging studies in patient selection. The success of recent endovascular trials was bolstered by the use of advanced imaging techniques for optimal selection of reperfusion candidates. This seminal juncture in the history of stroke trials warrants further consideration on the use of imaging to guide future refinements in the treatment of acute stroke. In this article, we systematically review the imaging methodology and key facets used in all published endovascular stroke trials to date, discuss the success of recent trials using latest advanced imaging techniques and focus on the importance of imaging studies for future patient selection.

Imaging of MELAS

Mitochondrial diseases are multisystem disorders that frequently involve the central nervous system. The clinical presentation of these disorders may be challenging to differentiate from cerebrovascular disorders. Various imaging techniques are now available that provide a wide range of imaging modalities during initial clinical evaluation and throughout the disease course. Recent technological advancements have introduced advanced neuroimaging modalities that provide detailed information of metabolic disorders at the tissue level. Imaging findings, though diverse, usually have characteristic features that support differentiating these disorders from vascular syndromes. This article provides an overview of various neuroimaging modalities available along with the advent of new imaging techniques being utilized in these disorders.

Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis

Background and Purpose— Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. Methods— We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. Results— We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41–2.16; P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01–1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00–1.40; P=0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04–1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03–1.47; P=0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93–1.52; P=0.16). Conclusions— Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.

The Role of Antithrombotics in Secondary Stroke Prevention

Antithrombotic therapy plays a key role in secondary ischemic stroke prevention. A multitude of antithrombotic agents exist with varying pharmacologic, efficacy, and safety profiles. In this review, the authors discuss the mechanisms of antithrombotic therapy, summarize the data on commonly used agents, and introduce emerging antithrombotic medications.

Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion

Objective In this multicenter study, we sought to evaluate comparative safety and efficacy of combined IV thrombolysis (IVT) and mechanical thrombectomy (MT) vs direct MT in emergent large vessel occlusion (ELVO) patients. Methods Consecutive ELVO patients treated with MT at 6 high-volume endovascular centers were evaluated. Standard safety and efficacy outcomes (successful reperfusion [modified Thrombolysis in Cerebral Infarction IIb/III], functional independence [FI] [modified Rankin Scale (mRS) score of 0–2 at 3 months], favorable functional outcome [mRS of 0–1 at 3 months], functional improvement [mRS shift by 1-point decrease in mRS score]) were compared between patients who underwent combined IVT and MT vs MT alone. Additional propensity score–matched analyses were performed. Results A total of 292 and 277 patients were treated with combination therapy and direct MT, respectively. The combination therapy group had greater functional improvement (p = 0.037) at 3 months. After propensity score matching, 104 patients in the direct MT group were matched to 208 patients in the combination therapy group. IVT pretreatment was independently (p < 0.05) associated with higher odds of FI (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.02–2.99) and functional improvement (common OR 1.64; 95% CI 1.05–2.56). Combination therapy was independently (p < 0.05) related to lower likelihood of 3-month mortality (0.50; 95% CI 0.26–0.96). Conclusions This observational study provides preliminary evidence that IVT pretreatment may improve outcomes in ELVO patients treated with MT. The question of the potential effect of IVT on ELVO patients treated with MT should be addressed with a randomized controlled trial. Classification of evidence This study provides Class III evidence that for stroke patients with emergent large vessel occlusion, combined IVT and MT is superior to direct MT in improving functional outcomes.

Reporting Compliance of Stroke Trials: Cross-Sectional Analysis

BACKGROUND The FDA mandates timely reporting of all clinical trials conducted in the United States. However, often the results are not reported in a timely manner, resulting in wastage of finite resources. We assessed the reporting of results of completed stroke trials and compared the reporting trends between U.S. and non-U.S. stroke trials. METHODS We assessed consecutive clinical stroke trials registered as completed in ClinicalTrials.gov between January 1, 2008 and January 1, 2015. Descriptive data collected included study phase, study type, participant age, number of enrolled patients, study locations, start and primary completion dates, result availability, time to reporting (months), sponsorship, funding sources, and publication status. We also performed manual search for stroke trials in Pubmed, Web of Science, and Google scholar. RESULTS Out of a total 140 completed trials, 39 trials (35,359 patients) involved at least 1 U.S. center and 101 trials (58,542 patients) were conducted in non-U.S. centers. Of the trials involving at least a single U.S. center, 31 of 39 (79%) reported their results, whereas only 6 of 31 (19%) reported their results within 1 year. Of the trials conducted at non-U.S. centers, 72 of 101 (71%) reported their results, whereas results for 24 of 72 (33%) trials were available within a year of completion. The time to reporting of results was significantly lower for all the included clinical trials in the 2012-2014 period (P < .001, Cohens d = .726) as compared to the 2008-2011 period. CONCLUSION Only one-fifth of completed stroke trials involving at least a single U.S. center report their results within 1 year. Additionally, every fifth completed trial involving stroke patients at U.S. centers remain unreported.

Unusual case of recurrent SMART (stroke-like migraine attacks after radiation therapy) syndrome

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cerebral radiation therapy. A 53-year-old female initially presented with headache, confusion and left homonymous hemianopia. Her medical history was notable for cerebellar hemangioblastoma, which was treated with radiation in 1987. Her initial brain MRI (magnetic resonance imaging) revealed cortical enhancement in the right temporo-parieto-occipital region. She improved spontaneously in 2 weeks and follow-up scan at 4 weeks revealed no residual enhancement or encephalomalacia. She presented 6 weeks later with aphasia. Her MRI brain revealed similar contrast-enhancing cortical lesion but on the left side. Repeat CSF studies was again negative other than elevated protein. She was treated conservatively and recovered completely within a week. Before diagnosing SMART syndrome, it is important to rule out tumor recurrence, encephalitis, posterior reversible encephalopathy syndrome (PRES) and stroke. Typically the condition is self-limiting, and gradually resolves.

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage

Background Magnesium (Mg) has potential hemostatic properties. We sought to investigate the potential association of serum Mg levels (at baseline and at 48 hours) with outcomes in patients with acute spontaneous intracerebral hemorrhage (ICH). Methods and Results We reviewed data on all patients with spontaneous ICH with available Mg levels at baseline, over a 5‐year period. Clinical and radiological outcome measures included initial hematoma volume, admission National Institutes of Health Stroke Scale and ICH scores, in‐hospital mortality, favorable functional outcome (modified Rankin Scale scores, 0–1), and functional independence (modified Rankin Scale scores, 0–2) at discharge. Our study population consisted of 299 patients with ICH (mean age, 61±13 years; mean admission serum Mg, 1.8±0.3 mg/dL). Increasing admission Mg levels strongly correlated with lower admission National Institutes of Health Stroke Scale score (Spearmans r, −0.141; P=0.015), lower ICH score (Spearmans r, −0.153; P=0.009), and lower initial hematoma volume (Spearmans r, −0.153; P=0.012). Higher admission Mg levels were documented in patients with favorable functional outcome (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.025) and functional independence (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.022) at discharge. No association between serum Mg levels at 48 hours and any of the outcome variables was detected. In multiple linear regression analyses, a 0.1‐mg/dL increase in admission serum Mg was independently and negatively associated with the cubed root of hematoma volume at admission (regression coefficient, −0.020; 95% confidence interval, −0.040 to −0.000; P=0.049) and admission ICH score (regression coefficient, −0.053; 95% confidence interval, −0.102 to −0.005; P=0.032). Conclusions Higher admission Mg levels were independently related to lower admission hematoma volume and lower admission ICH score in patients with acute spontaneous ICH.

Restrictive Arteriopathy in Late-Onset Pompe Disease: Case Report and Review of the Literature

Late-onset Pompe disease (LOPD) is an adult type of classical Pompe disease and presents without cardiomyopathy. Neuroimaging in LOPD is typically limited to posterior circulation and involves dilative arteriopathy, especially dolichoectasia and intracranial aneurysms. We report an interesting case of an established diagnosis of asymptomatic LOPD in a young man with a restrictive-variant pattern in posterior vasculature. We discuss the clinical presentation, neuroimaging, existing literature, and prognosis in vascular variants of LOPD.

Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review

Background Since large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death. Methods To delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3–6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset. Results Among 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3–6) within 3–6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53–5.63, p < 0.0001). Mortality within 3–6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5–6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8–55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8–81.3%) of poststroke dependence or death and 95.6% (CI: 89.0–98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality. Conclusion LVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.