Limiting Brain Shift in Malignant Hemispheric Infarction by Decompressive Craniectomy.

OBJECTIVE: Decompressive craniectomy (DC) improves functional outcomes in selected patients with malignant hemispheric infarction (MHI), but variability in the surgical technique and occasional complications may be limiting the effectiveness of this procedure. Our aim was to evaluate predefined perioperative CT measurements for association with post-DC midline brain shift in patients with MHI. METHODS: At two medical centers we identified 87 consecutive patients with MHI and DC between January 2007 and December 2019. We used our previously tested methods to measure the craniectomy surface area, extent of transcalvarial brain herniation, thickness of tissues overlying the craniectomy, diameter of the cerebral ventricle atrium contralateral to the stroke, extension of infarction beyond the craniectomy edges, and the pre and post-DC midline brain shifts. To avoid potential confounding from medical treatments and additional surgical procedures, we excluded patients with the first CT delayed >30 hours post-DC, resection of infarcted brain, or insertion of an external ventricular drain during DC. The primary outcome in multiple linear regression analysis was the postoperative midline brain shift. RESULTS: We analyzed 72 qualified patients. The average midline brain shift decreased from 8.7 mm pre-DC to 5.4 post-DC. The only factors significantly associated with post-DC midline brain shift at the p<0.01 level were preoperative midline shift (coefficient 0.32, standard error 0.10, p=0.002) and extent of transcalvarial brain herniation (coefficient -0.20, standard error 0.05, p <0.001). CONCLUSIONS: In patients with MHI and DC, smaller post-DC midline shift is associated with smaller pre-DC midline brain shift and greater transcalvarial brain herniation. This knowledge may prove helpful in assessing DC candidacy and surgical success. Additional studies to enhance the surgical success of DC are warranted.

Case report of optic atrophy in Dentatorubropallidoluysian Atrophy (DRPLA).

BACKGROUND: Dentatorubropallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease that is associated with numerous movement disorders. Ocular problems also occur with DRPLA with reports of corneal endothelial degeneration in some patients living with the disease. We report a new visual problem associated with DRPLA, optic atrophy. CASE PRESENTATION: A 47 year-old man presented complaining of progressive visual loss associated with optic atrophy on ophthalmological evaluation. He gradually developed a progressive ataxia with dystonia. Brain MRI revealed a diffuse leukoencephalopathy. Genetic analysis revealed 62 CAG repeats in one allele of the DRPLA gene and he was diagnosed with DRPLA. CONCLUSION: Optic atrophy should be included in the clinical spectrum of DRPLA.

Timeliness of intravenous thrombolysis via telestroke in Georgia.

BACKGROUND AND PURPOSE: Through 2-way live video and audio communication, telestroke enhances urgent treatment of patients with acute stroke in emergency departments (EDs) without immediate access to on-site specialists. To assess for opportunities to shorten the door to thrombolysis time, we measured multiple time intervals in a telestroke system. METHODS: We retrospectively analyzed 115 records of consecutive acute stroke patients treated with intravenous thrombolysis during a 20-month period via a statewide telestroke system in 17 EDs in Georgia. On the basis of times documented in the telestroke system, we calculated the time elapsed between the following events: ED arrival, telestroke patient registration, start of specialist consultation, head computed tomography, thrombolysis recommendation, and thrombolysis initiation. RESULTS: The most conspicuous delay was from ED arrival to telestroke patient registration (median, 39 minutes; interquartile range, 21-56). Median time from ED arrival to thrombolysis initiation was 88 minutes, interquartile range 75 to 105. Thrombolysis was initiated within 60 minutes from ED arrival in 13% of patients. CONCLUSIONS: The greatest opportunity to expedite acute thrombolysis via telestroke is by shortening the time from ED arrival to telestroke patient registration.

Simplified modified Rankin Scale questionnaire correlates with stroke severity.

OBJECTIVE: To further validate the simplified modified Rankin Scale questionnaire (smRSq), we compare it here to a well-established predictor of functional outcome after stroke, the initial stroke severity. DESIGN: Retrospective correlation analysis. PARTICIPANTS: Forty patients identified from a registry of stroke patients treated with intravenous tissue plasminogen activator. SETTING: Community and 17 hospital Emergency Departments within a web-based telestroke network throughout the state of Georgia, USA. MEASURES: Five certified raters assessed the initial stroke severities with the National Institutes of Health Stroke Scale (NIHSS) via the telestroke system. Over a 20 month period, one certified rater, unaware of the NIHSS scores, attempted to contact each patient in the registry to assess their functional outcomes with the smRSq via telephone. We analyzed patients who had the smRSq assessment at least three months after stroke. RESULTS: Forty of 120 registered patients were contacted and qualified for this study. The baseline clinical characteristics of the 40 analyzed and the 80 disqualified patients were similar. The correlation between the initial NIHSS and the smRSq was good (r = 0.69, R(2) = 0.47, P < 0.001). CONCLUSIONS: The good correlation of the smRSq with the initial stroke severity further confirms the smRSq validity in assessing functional outcome after stroke.

Distribution of cerebral age-related white matter changes in relation to risk factors in stroke patients.

INTRODUCTION: The distribution of cerebral age-related white matter changes (ARWMC) may be indicative of the underlying etiology and could suggest optimal interventions. We aimed to determine if left ventricular hypertrophy (LVH), a marker of uncontrolled hypertension, along with additional risk factors are associated with the distribution of cerebral ARWMC. METHODS: We analyzed data of 172 patients from a hospital stroke registry who had acute stroke and brain MRI. We classified lesion location as superficial (frontal, parieto-occipital, or temporal) or deep (basal nuclei) using the ARWMC scale. We defined a superficial ARWMC index as the superficial minus the deep score. We excluded infratentorial lesions and patients with bilateral strokes. Regression analysis analyzed LVH and other relevant clinical factors for independent association with the superficial ARWMC index. RESULTS: The superficial ARWMC scores ranged from 0 to 6, the deep scores from 0 to 3, and the superficial ARWMC index from -2 to 6. We categorized the superficial ARWMC index as -2 to 1 (n = 65), 2 (n = 50), and 3 - 6 (n = 57). In bivariate analysis, ARWMC distribution was significantly associated with older age, lower household income (HI), and lower serum triglyceride (TG) levels. In multiple logistic regression analysis, higher superficial ARWMC index was significantly associated with lower HI (OR 10.72, 95 % CI 2.30-49.85), lower serum low density cholesterol (LDL) (OR 0.86, 95 % CI 0.75-0.98, per 10 mg/dL), and lower serum TG levels (OR 0.91, 95 % CI 0.85-0.99, per 10 mg/dL). The area under the curve in receiver operating characteristic analysis (95 % CI) for HI was 0.63 (0.49-0.76), LDL level 0.64 (0.51-0.77), and TG level 0.77 (0.65-0.88). CONCLUSION: In this study, LVH was not associated with the distribution of cerebral ARWMC. Using an alternate classification of ARWMC distribution and analyzing additional risk factors in larger studies may yield further discoveries.

Impact of primary stroke center certification on location of acute ischemic stroke care in Georgia.

BACKGROUND AND PURPOSE: Primary stroke centers (PSCs) are associated with greater rates of tissue plasminogen activator use and improved outcomes. The American Stroke Association has advocated for the preferential transport of stroke patients to PSCs. We investigated the impact of PSC certification on hospital stroke discharge patterns in Georgia communities with a choice between PSC and non-PSC. METHODS: We analyzed data from the Georgia Discharge Data System before (2004) and after stroke certification (2009). Only Metropolitan Statistical Areas containing ≥1 PSC and ≥1 non-PSC were included in the analysis. We calculated the odds of acute stroke discharge from a PSC in 2009 compared with 2004. RESULTS: In Georgia Metropolitan Statistical Areas with at least 1 PSC and 1 non-PSC hospital, the percent of patients discharged from a subsequently designated PSC increased from 50.2% to 56.6% between 2004 and 2009 (OR, 1.29; P<0.0001). In 4 Metropolitan Statistical Areas, the proportion of stroke discharges from PSCs increased, whereas in 2 Metropolitan Statistical Areas, there was no significant increase, and in 1, there was a trend toward less stroke discharges from PSCs. CONCLUSIONS: Although there has been an overall increase in stroke discharges from PSCs, the impact of stroke certification on patient destination was small and inconsistent across the state suggesting that local factors influence the location of hospitalization.

A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes.

BACKGROUND AND PURPOSE: There is debate regarding the approach for analysis of modified Rankin scale scores, the most common functional outcome scale used in acute stroke trials. METHODS: We propose to use tests to assess treatment differences addressing the metric, "if a patient is chosen at random from each treatment group and if they have different outcomes, what is the chance the patient who received the investigational treatment will have a better outcome than will the patient receiving the standard treatment?" This approach has an associated statement of treatment efficacy easily understood by patients and clinicians, and leads to statistical testing of treatment differences by tests closely related to the Mann-Whitney U test (Wilcoxon Rank-Sum test), which can be tested precisely by permutation tests (randomization tests). RESULTS: We show that a permutation test is as powerful as are other approaches assessing ordinal outcomes of the modified Rankin scores, and we provide data from several examples contrasting alternative approaches. DISCUSSION: Whereas many approaches to analysis of modified Rankin scores outcomes have generally similar statistical performance, this proposed approach: captures information from the ordinal scale, provides a powerful clinical interpretation understood by both patients and clinicians, has power at least equivalent to other ordinal approaches, avoids assumptions in the parameterization, and provides an interpretable parameter based on the same foundation as the calculation of the probability value.

Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage.

BACKGROUND AND PURPOSE: The effectiveness of prothrombin complex concentrate (PCC) products available in the United States that contain low levels of factor VII (3-factor PCC) has not been tested. The purpose of this study was to review our experience with 3-factor PCC (Profilnine) in the setting of warfarin-associated intracranial hemorrhage (wICH). METHODS: In November 2007, we implemented a protocol for reversal of anticoagulation in wICH using Profilnine. Additional treatment with fresh-frozen plasma was at the discretion of the treating physician. Medical records of all patients receiving PCC for wICH between November 1, 2007, and December 7, 2011 were reviewed. Correction of the international normalized rate (INR) was defined as an INR <1.4. RESULTS: Seventy wICH patients were treated with Profilnine, including 46 (66%) with intraparenchymal hemorrhage, 22 (31%) with subdural hemorrhage, and 2 (3%) with subarachnoid hemorrhage. Mean INR was reduced from 3.36 to 1.96, and in 44 (62.9%) patients the INR corrected to <1.4. Baseline INR ≥3.0 decreased the likelihood of INR correction. Concomitant administration of fresh-frozen plasma (mean, 2.6 U) did not increase the likelihood of INR correction. Seven (10%) patients had serious adverse events during their hospital course, including 2 sudden deaths from suspected pulmonary embolism. CONCLUSIONS: Reversal of coagulopathy in wICH with Profilnine was incomplete and associated with serious adverse events. In the absence of available 4-factor PCC, options for urgent reversal of anticoagulation in wICH remain limited.

Predicting Functional Outcome After Decompressive Craniectomy for Malignant Hemispheric Infarction: Clinical and Novel Imaging Factors.

OBJECTIVE: Decompressive craniectomy (DC) is an established optional treatment for malignant hemispheric infarction (MHI). We analyzed relevant clinical factors and computed tomography (CT) measurements in patients with DC for MHI to identify predictors of functional outcome 3-6 months after stroke. METHODS: This study was performed at 2 comprehensive stroke centers. The inclusion criteria required DC for MHI, no additional intraoperative procedures (strokectomy or cerebral ventricular drain placement), and documented functional status 3-6 months after the stroke. We classified functional outcome as acceptable if the modified Rankin Scale score was <5, or as unacceptable if it was 5 or 6 (bedbound and totally dependent on others or death). Multiple logistic regression analyzed relevant clinical factors and multiple perioperative CT measurements to identify predictors of acceptable functional outcome. RESULTS: Of 87 identified consecutive patients, 66 met the inclusion criteria. Acceptable functional outcome occurred in 35 of 66 (53%) patients. Likelihood of acceptable functional outcome decreased significantly with increasing age (OR 0.92, 95% CI 0.82-0.97, P = 0.004) and with increasing post-DC midline brain shift (OR 0.78, 95% CI 0.64-0.96, P = 0.016), and decreased non-significantly with left-sided stroke (OR 0.30, 95% CI 0.08-1.10, P = 0.069) and with increasing craniectomy barrier thickness (OR 0.92, 95% CI 0.85-1.01, P = 0.076). CONCLUSIONS: Patient age and the post-DC midline shift may be useful in prognosticating functional outcome after DC for MHI. Stroke side and craniectomy barrier thickness merit further ideally prospective outcome prediction testing.

Simplified modified rankin scale questionnaire: reproducibility over the telephone and validation with quality of life.

BACKGROUND AND PURPOSE: The simplified modified Rankin Scale questionnaire (smRSq) enables a reliable and rapid determination of the modified Rankin Scale score after stroke. We test the reliability and validity of a slightly revised smRSq. METHODS: Fifty consecutive outpatients 4.83 ± 3.00 months after stroke were scored with a slightly revised smRSq by 3 raters selected consecutively from a list of 10: 4 stroke faculty, 3 neurology residents, 2 medial students, and 1 stroke research coordinator. Two ratings were in person within 20 minutes of each other and 1 was by telephone 1 to 3 days later. The telephone rating also included a quality of life scale, the Short-Form-12v2. Each rater was blinded to the other raters' scores. RESULTS: The average estimated time to administer the smRSq was 1.29 minutes (range, 0.50 to 2.25 minutes). The in-person raters agreed 78% (κ=0.71; CI, 0.57 to 0.86 and weighted κ [κ(w)]=0.86; CI, 0.79 to 0.94). The first in-person and telephone raters agreed 82% (κ=0.76; CI, 0.63 to 0.90 and κ(w)=0.87; CI, 0.79 to 0.95). The second in-person and telephone rates agreed 82% (κ=0.77; CI, 0.63 to 0.90 and κ(w)=0.89; CI, 0.82 to 0.96). The smRSq correlated with the physical (r=-0.50, P=0.005) than the mental (r=-0.36, P=0.048) components of the Short-Form-12v2. CONCLUSIONS: The slightly revised smRSq appears to be useful in clinical stroke; it has excellent reliability in person and by telephone, can usually be administered in <1.5 minutes by a wide variety of raters, and correlates with quality of life.

A telestroke network enhances recruitment into acute stroke clinical trials.

BACKGROUND AND PURPOSE: Acute stroke clinical trials are conducted primarily at academic medical centers. As a result, patients living in rural areas are excluded from participation, results may not be generalizable to nonacademic settings, and studies may be slow to recruit subjects. Telemedicine can provide rural patients with emergency neurovascular consultation. We sought to determine whether telemedicine facilitates enrollment into acute stroke trials. METHODS: We have an established rural "hub and spoke" telestroke network. From 2005 to 2009, we participated in 2 time-sensitive acute stroke trials: Factor Seven for Acute Hemorrhagic Stroke and Minocycline to Improve Neurological Outcome. Candidates for the 2 trials could be identified at either the hub or at the spokes, with patients presenting to the latter transferred to the hub for enrollment. We analyzed the times from symptom onset to consultation via telemedicine, arrival at the hub, and to initiation of a study drug to determine the impact of telemedicine on study enrollment. RESULTS: Nineteen of 28 subjects enrolled in the 2 trials were identified initially at an outside facility via a telemedicine link. An additional 9 candidates identified by telemedicine could not be enrolled because of transportation time. Arrival at the hub was 127 minutes later (median, 207 [95% CI, 145 to 255] versus 80 [95% CI, 55 to 142]; P=0.0002), and study drug was started 74 minutes later (median, 298 [95% CI, 218 to 352] versus 225 [95% CI, 147 to 330]; P=0.05) for subjects who were identified via telemedicine and required transport to the hub compared with local subjects who presented directly to the hub. CONCLUSIONS: Telemedicine can enhance enrollment into time-sensitive acute stroke trials. However, transfer of subjects to the hub results in delays in study initiation for some and precludes enrollment for others similar to the weaknesses of "ship and drip" thrombolytic strategies. To save time, efforts are needed to enroll clinical trial subjects and begin the research drug at the remote site under telemedicine guidance.

Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study.

BACKGROUND AND PURPOSE: Minocycline is a promising anti-inflammatory and protease inhibitor that is effective in multiple preclinical stroke models. We conducted an early phase trial of intravenous minocycline in acute ischemic stroke. METHODS: Following an open-label, dose-escalation design, minocycline was administered intravenously within 6 hours of stroke symptom onset in preset dose tiers of 3, 4.5, 6, or 10 mg/kg daily over 72 hours. Minocycline concentrations for pharmacokinetic analysis were measured in a subset of patients. Subjects were followed for 90 days. RESULTS: Sixty patients were enrolled, 41 at the highest dose tier of 10 mg/kg. Overall age (65±13.7 years), race (83% white), and sex (47% female) were consistent across the doses. The mean baseline National Institutes of Health Stroke Scale score was 8.5±5.8 and 60% received tissue plasminogen activator. Minocycline infusion was well tolerated with only 1 dose limiting toxicity at the 10-mg/kg dose. No severe hemorrhages occurred in tissue plasminogen activator-treated patients. Pharmacokinetic analysis (n=22) revealed a half-life of approximately 24 hours and linearity of parameters over doses. CONCLUSIONS: Minocycline is safe and well tolerated up to doses of 10 mg/kg intravenously alone and in combination with tissue plasminogen activator. The half-life of minocycline is approximately 24 hours, allowing every 24-hour dosing. Minocycline may be an ideal agent to use with tissue plasminogen activator.

Improving modified Rankin Scale assessment with a simplified questionnaire.

BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is a popular primary stroke outcome measure, but its usefulness is limited by suboptimal reliability (inter-rater agreement). METHODS: We developed and tested the reliability of a simplified mRS questionnaire (smRSq) in 50 patients after stroke seen in outpatient clinics. Randomly chosen paired raters administered the smRSq within 20 minutes of each other and the ratings were blinded until the end of this study. RESULTS: Agreement among the raters was 78%, the kappa statistic was 0.72 (95% CI, 0.58-0.86), and the weighted kappa(w) statistic taking into account the extent of disagreement was 0.82 (95% CI, 0.72-0.92). The average time to administer the smRSq was 1.67 minutes. CONCLUSIONS: The smRSq appears to have very good reliability that is similar to that of a structured interview mRS and is considerably less time-consuming.

New CT measurements to assess decompression after hemicraniectomy: A two-center reliability study.

OBJECTIVES: To test the reliability of three simplified measurements made after decompressive hemicraniectomy (DHC) for malignant hemispheric infarction on computed tomography (CT) scan. PATIENTS AND METHODS: We defined new simple methods to measure the thickness of the soft tissues overlying the craniectomy defect and the extent of infarction beyond the anterior and posterior craniectomy edges on post-DHC CT. Multiple raters independently made the three new CT measurements in 49 patients from two institutions. The Intraclass Correlation Coefficient (ICC) compared the raters for interrater agreements (reliability). RESULTS: Between two raters at Augusta University Medical Center, each measuring 21 CT scans, the ICC coefficient point estimates were good to excellent (0.83 - 0.92). Among four raters at University of Virginia Medical Center, with three raters measuring each of 28 CT scans, the ICC coefficient point estimates were good to excellent (0.87 - 0.95). CONCLUSIONS: The proposed simple methods to obtain three additional CT measurements after DHC in malignant hemispheric infarction have good to excellent reliability in two independent patient samples. The clinical usefulness of these measurements should be investigated.

A web-based telestroke system facilitates rapid treatment of acute ischemic stroke patients in rural emergency departments.

Patients in rural communities lack access to acute stroke therapies. Rapid administration of thrombolytic therapy increases the likelihood of a favorable outcome in ischemic stroke. We aimed to detail the safety, feasibility, and treatment times of thrombolytic therapy with a web-based telestroke system. At the Medical College of Georgia, we have developed a telestroke system (Remote Evaluation of Acute IsCHemic Stroke; REACH) in which emergency physicians in surrounding counties may consult stroke specialists at our institution. The web-based system allows the stroke consultant to obtain history, examine the patient with live video, and review computed tomography. A recommendation is made regarding the administration of tissue plasminogen activator (tPA) before patient transport to the tertiary medical center. A systematic review of the literature was conducted regarding the use of tPA in academic and community hospitals. Symptomatic hemorrhagic transformation and stroke onset-to-treatment times were compared between the REACH network and other stroke care delivery systems. Between February 2003 and March 2006, 50 patients were treated with intravenous tPA using the REACH telestroke system. There was one (2%) symptomatic hemorrhage. The mean onset-to-treatment time was 127.6 min (95% confidence interval 117.1-138.0) using REACH compared with 145.9 min (95% confidence interval 126.9-164.9) in our Emergency Department and 147.8 min in other published systems. REACH, a web-based telestroke system, facilitates the safe administration of thrombolytic therapy to patients within rural communities suffering an acute ischemic stroke.

Are limb-shaking transient ischemic attacks a risk factor for postendarterectomy hemorrhage? Case report and literature review.

Postoperative intracerebral hemorrhage occurs in about 0.5% of all carotid endarterectomies. There are no recognized risk factors for this complication. We report on a 74-year-old woman with right sided limb-shaking transient ischemic attacks and severe stenosis of the left internal carotid artery. She suffered a fatal intracerebral hemorrhage 11 days after endarterectomy. This case prompted a review of the literature to determine if limb-shaking transient ischemic attacks might be a risk factor for postoperative intracerebral hemorrhage. We propose that patients with limb-shaking transient ischemic attacks have loss of vasomotor reactivity placing them at high risk for carotid reperfusion syndrome and hemorrhage into the revascularized territory.

A Simplified Quantitative Method to Measure Brain Shifts in Patients with Middle Cerebral Artery Stroke.

BACKGROUND AND PURPOSE: A standardized and validated method to measure brain shifts in malignant middle cerebral artery (MCA) stroke with decompressive hemicraniectomy (DHC) could facilitate clinical decision making, prognostication, and comparison of results between studies. METHODS: We tested for reliability simplified methods to measure transcalvarial herniation, midline brain shift, and the contralateral cerebral ventricular atrium in malignant MCA stroke after DHC. Multiple raters measured brain shifts on post-DHC computed tomography (CT) scans with aligned and unaligned slice orientations in 25 patients. We compared the simplified measurements to previously reported more meticulous measurements. RESULTS: The simplified measurements correlate well with the more meticulous measurements on both aligned and unaligned CTs (intraclass correlation coefficients .72-.89). CONCLUSIONS: These simplified and expedient methods of measuring brain shifts in malignant MCA stroke after DHC correlate well with the more meticulous methods.