Small Vessel Cerebrovascular Disease: The Past, Present, and Future

Brain infarction due to small vessel cerebrovascular disease (SVCD)—also known as small vessel infarct (SVI) or “lacunar” stroke—accounts for 20% to 25% of all ischemic strokes. Historically, SVIs have been associated with a favorable short-term prognosis. However, studies over the years have demonstrated that SVCD/SVI is perhaps a more complex and less benign phenomenon than generally presumed. The currently employed diagnostic and therapeutic strategies are based upon historical and contemporary perceptions of SVCD/SVI. What is discovered in the future will unmask the true countenance of SVCD/SVI and help furnish more accurate prognostication schemes and effective treatments for this condition. This paper is an overview of SVCD/SVI with respect to the discoveries of the past, what is known now, and what will the ongoing investigations evince in the future

Small Vessel Cerebrovascular Disease: The Past, Present, and Future

Brain infarction due to small vessel cerebrovascular disease (SVCD)-also known as small vessel infarct (SVI) or "lacunar" strokeaccounts for 20% to 25% of all ischemic strokes. Historically, SVIs have been associated with a favorable short-term prognosis. However, studies over the years have demonstrated that SVCD/SVI is perhaps a more complex and less benign phenomenon than generally presumed. The currently employed diagnostic and therapeutic strategies are based upon historical and contemporary perceptions of SVCD/SVI. What is discovered in the future will unmask the true countenance of SVCD/SVI and help furnish more accurate prognostication schemes and effective treatments for this condition. This paper is an overview of SVCD/SVI with respect to the discoveries of the past, what is known now, and what will the ongoing investigations evince in the future

Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest

BACKGROUND AND PURPOSE: Anecdotal reports suggest that a loss of distinction between gray (GM) and white matter (WM) as adjudged by CT scan predicts poor outcome in comatose patients after cardiac arrest. To address this, we quantitatively assessed GM and WM intensities at various brain levels in comatose patients after cardiac arrest. METHODS: Patients for whom consultation was requested within 24 hours of a cardiac arrest were identified with the use of a computerized database that tracks neurological consultations at our institution. Twenty-five comatose patients were identified for whom complete medical records and CT scans were available for review. Twenty-five consecutive patients for whom a CT scan was interpreted as normal served as controls. Hounsfield units (HUs) were measured in small defined areas obtained from axial images at the levels of the basal ganglia, centrum semiovale, and high convexity area. RESULTS: At each level tested, lower GM intensity and higher WM intensity were noted in comatose patients compared with normal controls. The GM/WM ratio was significantly lower among comatose patients compared with controls (P:\u3c0.0001, rank sum test). There was essentially no overlap in GM/WM ratios between control and study patients. The difference was greatest at the basal ganglia level. We also observed a marginally significant difference in the GM/WM ratio at the basal ganglia level between those patients who died and those who survived cardiac arrest (P:=0. 035, 1-tailed t test). Using receiver operating characteristic curve analysis, we determined that a difference in GM/WM ratio of \u3c1.18 at the basal ganglia level was 100% predictive of death. At the basal ganglia level, none of 12 patients below this threshold survived, whereas the survival rate was 46% among patients in whom the ratio was \u3e1.18. The empirical risk of death was 21.67 for comatose patients with a value below threshold. CONCLUSIONS: The ratio in HUs of GM to WM provides a reproducible measure of the distinction between gray and white matter. A lower GM/WM ratio is observed in comatose patients immediately after cardiac arrest. The basal ganglia level seems to be the most sensitive location on CT for measuring this relationship. Although a GM/WM ratio \u3c1.18 at this level predicted death in this retrospective study, the difference in this study is not robust enough to recommend that management decisions be dictated by CT results. The results, however, do warrant consideration of a prospective study to determine the reliability of CT scanning in predicting outcome for comatose patients after cardiac arrest

Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome

Background and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events

Spreading Depolarization as a Therapeutic Target in Severe Ischemic Stroke: Physiological and Pharmacological Strategies

Background: Spreading depolarization (SD) occurs nearly ubiquitously in malignant hemispheric stroke (MHS) and is strongly implicated in edema progression and lesion expansion. Due to this high burden of SD after infarct, it is of great interest whether SD in MHS patients can be mitigated by physiologic or pharmacologic means and whether this intervention improves clinical outcomes. Here we describe the association between physiological variables and risk of SD in MHS patients who had undergone decompressive craniectomy and present an initial case of using ketamine to target SD in MHS. Methods: We recorded SD using subdural electrodes and time-linked with continuous physiological recordings in five subjects. We assessed physiologic variables in time bins preceding SD compared to those with no SD. Results: Using multivariable logistic regression, we found that increased ETCO2 (OR 0.772, 95% CI 0.655&ndash;0.910) and DBP (OR 0.958, 95% CI 0.941&ndash;0.991) were protective against SD, while elevated temperature (OR 2.048, 95% CI 1.442&ndash;2.909) and WBC (OR 1.113, 95% CI 1.081&ndash;1.922) were associated with increased risk of SD. In a subject with recurrent SD, ketamine at a dose of 2 mg/kg/h was found to completely inhibit SD. Conclusion: Fluctuations in physiological variables can be associated with risk of SD after MHS. Ketamine was also found to completely inhibit SD in one subject. These data suggest that use of physiological optimization strategies and/or pharmacologic therapy could inhibit SD in MHS patients, and thereby limit edema and infarct progression. Clinical trials using individualized approaches to target this novel mechanism are warranted