Asymmetric TCD Findings in Malignant MCA Infarction, Resolution after Decompressive Hemicraniectomy: A Case Report

Transcranial Doppler (TCD) is a non-invasive method for assessing cerebral hemodynamics in the acute phase of stroke. We report a case of a 33-year-old man who presented with a massive left hemispheric infarct developing into “malignant” MCA infarction. TCD was utilized to monitor intracranial hemodynamics while the clinical and neuroimaging findings were used to help us in the decision to proceed with decompressive craniectomy (DC). Pre-operatively, there was reduced mean flow velocities (MFV) of the middle cerebral artery (MCA) with increasing pulsatility index (PI) ipsilateral to the infarct. The subsequent but smaller rise in the PI in the contralateral MCA was suggestive of very high intracranial pressure (ICP) from massive brain swelling. Serial TCD examinations post-operatively showed normalization of the PI, and subsequent rise in the left MCA MFV. Clinical improvement was also noted as the TCD findings improved. The asymmetry in TCD findings can be attributed to occlusion of the MCA with subsequent spontaneous recanalisation, occlusion of the MCA with subsequent recanalisation due to the DC, or initial occlusion and subsequent pressure effects on the arterioles of the MCA due to the “malignant” edema of that hemisphere that was relieved by DC. This case illustrates the value of TCD as a useful modality in monitoring intracranial hemodynamics in acute stroke.

Outcome After Decompressive Craniectomy for Middle Cerebral Artery Infarction: Timing of the Intervention

BACKGROUND Based on randomized controlled trials (RCTs), clinical guidelines for the treatment of space-occupying hemispheric infarct employ age (≤60 yr) and time elapsed since stroke onset (≤48 h) as decisive criteria whether to perform decompressive craniectomy (DC). However, only few patients in these RCTs underwent DC after 48 h. OBJECTIVE To study the association between the timing of DC and (un)favorable outcome in patients with space-occupying middle cerebral artery (MCA) infarct undergoing DC. METHODS We performed a single-center cohort study from 2007 to 2017. Unfavorable outcome at 1 yr was defined as a Glasgow outcome scale 1 to 3. Additionally, we systematically reviewed the literature up to November 2018, including studies reporting on the timing of DC and other predictors of outcome. We performed Firth penalized likelihood and random-effects meta-analysis with odds ratio (OR) on unfavorable outcome. RESULTS A total of 66 patients were enrolled. A total of 26 (39%) patients achieved favorable and 40 (61%) unfavorable outcomes (13 [20%] died). DC after 48 h since stroke diagnosis did not significantly increase the risk of unfavorable outcome (OR 0.8, 95% CI 0.3-2.3). Also, in the meta-analysis, DC after 48 h of stroke onset was not associated with a higher risk of unfavorable outcome (OR 1.11; 95% CI 0.89-1.38). CONCLUSION The outcome of DC performed after 48 h in patients with malignant MCA infarct was not worse than the outcome of DC performed within 48 h. Contrary to current guidelines, we, therefore, advocate not to set a restriction of ≤48 h on the time elapsed since stroke onset in the decision whether to perform DC.

Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial

ObjectiveIn this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints.MethodsBlinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined.ResultsIn the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 [58.5%] in IV glyburide vs n = 23 [63.9%] in placebo, p = 0.91) or the incidence of malignant edema (n = 19 [46%] in IV glyburide vs n = 17 [47%] in placebo, p = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 [2.4%] with IV glyburide vs n = 8 [22.2%] with placebo, p = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 9) levels (p < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 [37%] in IV glyburide vs n = 12 [71%] in placebo, p = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 [58%] vs n = 15 [94%], p = 0.016).ConclusionIV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings.ClinicalTrials.gov identifierNCT01794182.Level of evidenceThis study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.

Abstract TMP57: Cerebral Oxygen Metabolism as a Biomarker to Stratify Stroke Risk in Young Adults with Sickle Cell Disease

Background: While imaging biomarkers guide stroke prevention strategies in children with sickle cell (SC) disease, none have been adequately studied in adults. High oxygen extraction (OEF) predicts stroke in non-SC adults with carotid occlusion, while low oxygen metabolism (CMRO 2 ) predicts tissue at imminent risk in acute ischemic stroke. We hypothesized that metrics of cerebral metabolism: (1) differ between SC adults with and without stroke and (2) correlate with infarct burden. Methods: A prospective MRI study enrolled 37 adults (28 ± 8 yr) from SC clinic into 4 groups: (1) 9 age/race matched healthy controls, (2) 6 SC adults without infarcts, (3) 15 SC adults with infarcts (infarct volume 7.4 ± 17.5 ml), and (4) 7 SC adults on chronic transfusions (Tx) (infarct volume 3.6 ± 6.6 ml). Arterial spin labelling and asymmetric spin echo measured voxel-wise cerebral blood flow (CBF) and OEF. CMRO 2 = CBF x OEF x blood oxygen content. Infarcts were delineated on FLAIR. OEF, CBF, and CMRO 2 (excluding infarcted tissue) were compared: between groups 1-3 (Kruskal-Wallis) and in group 4 between pre- and post-tx scans (Signed Rank). An ROI defined by high OEF within the deep white matter (a region at high stroke risk in SC) was applied to group 3. OEF, CBF, and CMRO 2 within the ROI were correlated with hemispheric infarct volume (IV) (Spearman’s ρ ). Results: Whole brain OEF showed a stepwise increase from controls, to SC adults without stroke, to SC adults with stroke (P<.001). SC adults on chronic Tx had intermediate OEF, with lowering of OEF post-Tx (Fig A). CBF and CMRO 2 were similar for SC adults with and without stroke (Fig B, C). High OEF and low CBF/CMRO 2 in the ROI correlated with hemispheric infarct burden: IV vs. OEF ( ρ =.40, P=.043); IV vs. CBF ( ρ =-.61, P=.002); and IV vs. CMRO 2 ( ρ =-.50, P=.016). Conclusion: Global OEF holds promise to stratify stroke risk in SC disease. Regional metrics of cerebral oxygen metabolism may indicate tissue-specific metabolic stress at imminent risk of infarction.

Abstract 154: Protection from Transient Focal Cerebral Ischemia by Transfusion of Polynitroxylated Pegylated Hemoglobin

Polynitroxylation of hemoglobin (Hb) confers superoxide dismutase and catalase mimetic activity and can protect neurons from native Hb and glutamate. Here, we determined if transfusion of polynitroxylated pegylated Hb (PNPH) is protective in the rat filament model of 2 h of middle cerebral artery occlusion (MCAO). Transfusion of 10 ml/kg of PNPH at 20 min of MCAO reduced the median infarct volume in cerebral cortex from 40% (37-47% interquartile range; n=10) in controls to 3% (0-7%; n=10; P<0.001) with PNPH and in striatum from 78% (66-88%) to 34% (0-37%; P<0.001). The therapeutic window was evaluated in a second experiment. Compared to the control median hemispheric infarct volume of 22% (13-34%; n=15), infarct volume was reduced to 7% (3-13%; n=14; P<0.05) when PNPH was transfused at 4 h after MCAO (2 h of reperfusion) but not significantly when transfused at 6 h (8%; 3-35%; n=14) or at 8 h (12%; 10-25%; n=14) after MCAO. To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows during MCAO. With no transfusion, MCAO induced an initial dilation (36±5%; ±SD; n=8) that subsided by 2 h (5±11%). With PNPH transfusion at 20 min of MCAO, the initial dilation (31±8%; n=7) was better maintained at 2 h (21±11%; P<0.02). To determine whether delaying PNPH transfusion until 90 min of MCAO would improve penumbral perfusion, laser-Doppler flow (LDF) was measured in the ischemic border region where the reduction in LDF was less severe than in the core. LDF significantly increased from 48±18% of the pre-ischemic baseline to 67±21% (P<0.005). Thus, PNPH transfusion has a significant therapeutic window for protection from transient MCAO and may act, in part, by stabilizing vascular function and improving collateral blood flow.