No abstract

A solitAry occlusion at the M 2 segment of the middle cerebral artery (MCA) is identified as the cause of stroke in 9%-38% of patients in large thrombolysis series, thus accounting for 16%-41% of all MCA infarctions in this population. [1][2][3]5,8,9,11,13,[15][16][17][18] Unfortunately, the benefit of aggressive intraarterial (IA) intervention for M 2 occlusions remains unclear and the benefit-risk ratio is debatable. Compared with the M 1 segment of the MCA and the internal carotid artery (ICA), M 2 divisions are more distal vessels with smaller calibers and thinner walls. Thus, endovascular access can be more challenging and risky. Moreover, the involved vascular territory and ischemic penumbra are more limited in size, which inevitably translates into a narrower margin of benefit. In fact, reported recanalization rates in the literature have been highly variable, ranging from 43% to 82% 1,8,12,16,17 following IA therapy and from 31% to 68% following intravenous (IV) thrombolysis. Methods. Patients with a solitary M 2 occlusion were identified from the Prolyse in Acute Cerebral Thromboembolism (PROACT) II, Interventional Management of Stroke (IMS), and IMS II trial databases and were divided into 2 groups: successful reperfusion (thrombolysis in cerebral infarction [TICI] 2-3) at 2 hours and failed reperfusion (TICI 0-1) at 2 hours. Baseline characteristics and clinical outcomes were compared.Results. Sixty-three patients, 40 from PROACT II and 23 from IMS and IMS II, were identified. Successful early angiographic reperfusion (TICI 2-3) was observed in 31 patients (49.2%). No statistically significant difference in the rates of intracerebral hemorrhage (60.9% vs 47.6%, p = 0.55) or mortality (19.4% vs 15.6%, p = 0.75) was observed. However, there was a trend toward higher incidence of symptomatic hemorrhage in the TICI 2-3 group (17.4% vs 0%, p = 0.11). There was also a trend toward higher baseline glucose levels in this group (151.5 mg/dl vs 129.6 mg/ dl, p = 0.09). Despite these differences, the rate of functional independence (modified Rankin Scale Score 0-2) at 3 months was similar (TICI 2-3, 58.1% vs TICI 0-1, 53.1%; p = 0.80).Conclusions. A positive correlation between successful early reperfusion and clinical outcome could not be demonstrated for patients with M 2 occlusion. Irrespective of reperfusion status, such patients have better outcomes than those with more proximal occlusions, with more than 50% achieving functional independence at 3 months. (http://thejns.org/doi/abs/10.3171/2014.7.JNS131430) keY woRDS • acute ischemic stroke • intraarterial thrombolysis • middle cerebral artery • outcome • reperfusion • vascular disordersAbbreviations used in this paper: IA = intraarterial; ICA = internal carotid artery; ICH = intracerebral hemorrhage; IMS = Interventional Management of Stroke; IV = intravenous; MCA = middle cerebral artery; mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Scale; NINDS = National Institute of Neurological Disorders and Stroke; PROACT = Prolyse in...

BACKGROUND AND PURPOSE:The modified TICI score is the benchmark for quantifying reperfusion after mechanical thrombectomy. There has been limited investigation into the reliability of this score. We aim to identify intra-rater and inter-rater reliability of the mTICI score among endovascular neurosurgeons. MATERIALS AND METHODS:Four independent endovascular neurosurgeons (raters) reviewed angiograms of 67 patients at 2 time points. k statistics assessed inter-and intrarater reliability and compared raters'-versus-proceduralists' scores. Reliability was also assessed for occlusion location and by dichotomizing modified TICI scores (0-2a versus 2b-3). RESULTS:Interrater reliability was moderate-to-substantial, weighted k ¼ 0.417-0.703, overall k ¼ 0.374 (P , .001). The dichotomized modified TICI score had moderate-to-substantial interrater agreement, k statistics ¼ 0.468-0.715, overall k ¼ 0.582 (P , .001). Intrarater reliability was moderate-to-almost perfect, weighted k ¼ 0.594-0.81. The dichotomized modified TICI score had substantial-to-almost perfect reliability, k ¼ 0.632-0.82. Proceduralists had fair-to-moderate agreement with raters, weighted k ¼ 0.348-0.574, and the dichotomized modified TICI score had fair-to-moderate agreement, k ¼ 0.365-0.544. When proceduralists and raters disagreed, proceduralists' scores were higher in 79.6% of cases. M1 followed by ICA occlusions had the highest agreement. CONCLUSIONS:The modified TICI score is a practical metric for assessing reperfusion after mechanical thrombectomy, though not without limitations. Agreement improved when scores were dichotomized around the clinically relevant threshold of successful revascularization. Interrater reliability improved with time, suggesting that formal training of interventionalists may improve reporting reliability. Agreement of the modified TICI scale is best with M1 and ICA occlusion and becomes less reliable with more distal or posterior circulation occlusions. These findings should be considered when developing research trials.

Purpose Malignant middle cerebral artery (MCA) infarctions are thought to be rare in children. In a recent hospital-based study, only 1.3 % of pediatric ischemic strokes were malignant MCA infarctions. However, population-based rates have not been published. We performed subgroup analysis of a population-based study to determine the rate of malignant MCA infarctions in children. Methods In 2005 and 2010, all ischemic stroke-related emergency visits and hospital admissions among the 1.3 million residents of the five-county Greater Cincinnati/Northern Kentucky area were ascertained. Cases that occurred in patients 18 years and younger were reviewed in detail, and corresponding clinical and neuroimaging findings were recorded. Infarctions were considered malignant if they involved 50 % or more of the MCA territory and resulted in cerebral edema and mass effect. Results In 2005, eight pediatric ischemic strokes occurred in the study population, none of which were malignant infarctions. In 2010, there were also eight ischemic strokes. Of these, two malignant MCA infarctions were identified: (1) a 7-year-old boy who underwent hemicraniectomy and survived with moderate disability at 30 days and (2) a 17-year-old girl with significant prestroke disability who was not offered hemicraniectomy and died following withdrawal of care. Thus, among 16 children over 2 years, there were two malignant MCA infarctions (12.5 %, 95 % CI 0–29). Conclusions Malignant MCA infarctions in children may not be as rare as previously thought. Given the significant survival and functional outcome benefit conferred by hemicraniectomy in adults, future studies focusing on its potential role in pediatric patients are warranted.

Chronic cocaine use produces long-lasting changes in reward circuits that may underlie the transition from casual to compulsive patterns of drug use. Although strong neuroadaptations within the mesocorticolimbic system are known to occur, the specific role of these drug-induced plasticities on sensitization remains to be elucidated. Here we investigate whether PKMζ, a protein involved in maintaining long-term potentiation (LTP), plays a role in these cocaine-induced changes in synaptic strengthening. We performed whole-cell voltage clamp recordings of putative ventral tegmental area (VTA) dopamine (DA) cells 24 hours after five days of 15 mg/kg i.p. cocaine or isovolumetric saline injections. We observed that superfusion of 5µM ZIP (PKMζ inhibitory peptide) decreased AMPA currents and AMPA/NMDA ratios only in cocaine sensitized rats. In vivo ZIP microinfusions (10 nmol) into the VTA after cocaine sensitization decreased locomotor activity on a subsequent cocaine challenge only if given ZIP is given before the withdrawal period. On the other hand, ZIP microinfusions into the nucleus accumbens (NAc) core after a seven days withdrawal period disrupt the expression of locomotor sensitization. The present data provide a potentially relevant region, and time-specific PKMζ-dependent brain mechanism that enables sensitization. Our results support the vision that addiction involves a pathological learning process. They imply that if this synaptic strengthening is reversed, changes in the behavioral response may also be overturned.