P.A. Barber

Refining the Perfusion–Diffusion Mismatch Hypothesis

Background and Purpose— The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)–diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods— Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2Day 90-vol-DWIAcute-vol) were also assessed. Results— Mean age was 68±11, time to MRI 4.5±0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch ≥20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=−0.51; P=0.009). Conclusions— Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Cerebral Ischemic Lesions on Diffusion-Weighted Imaging Are Associated With Neurocognitive Decline After Cardiac Surgery

Background and Purpose— Improvements in cardiac surgery mortality and morbidity have focused interest on the neurological injury such as stroke and cognitive decline that may accompany an otherwise successful operation. We aimed to investigate (1) the rate of stroke, new ischemic change on MRI, and cognitive impairment after cardiac valve surgery; and (2) the controversial relationship between perioperative cerebral ischemia and cognitive decline. Methods— Forty patients (26 men; mean [SD] age 62.1 [13.7] years) undergoing intracardiac surgery (7 also with coronary artery bypass grafting) were studied. Neurological, neuropsychological, and MRI examinations were performed 24 hours before surgery and 5 days (MRI and neurology) and 6 weeks (neuropsychology and neurology) after surgery. Cognitive decline from baseline was determined using the Reliable Change Index. Results— Two of 40 (5%) patients had perioperative strokes and 22 of 35 (63%) tested had cognitive decline in at least one measure (range, 1 to 4). Sixteen of 37 participants (43%) with postoperative imaging had new ischemic lesions (range, 1 to 17 lesions) with appearances consistent with cerebral embolization. Cognitive decline was seen in all patients with, and 35% of those without, postoperative ischemic lesions (P<0.001), and there was an association between the number of abnormal cognitive tests and ischemic burden (P<0.001). Conclusion— We have provided a reliable estimate of the rate of stroke, postoperative ischemia, and cognitive impairment at 6 weeks after cardiac valve surgery. Cognitive impairment is associated with perioperative ischemia and is more severe with greater ischemic load.

Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra

Objectives: In acute ischemic stroke the pattern of a perfusion-imaging (PI) lesion larger than the diffusion-weighted imaging (DWI) lesion may be a marker of the ischemic penumbra. We hypothesized that acute middle cerebral artery (MCA) occlusion would predict the presence of presumed “penumbral” patterns (PI > DWI), ischemic core evolution, and stroke outcome. Methods: Echoplanar PI, DWI, and magnetic resonance angiography (MRA) were performed in 26 patients with MCA territory stroke. Imaging and clinical studies (Canadian Neurological Scale, Barthel Index, and Rankin Scale) were performed within 24 hours of onset and repeated at days 4 and 90. Results: MCA flow was absent in 9 of 26 patients. This was associated with larger acute PI and DWI lesions, greater PI/DWI mismatch, early DWI lesion expansion, larger final infarct size, worse clinical outcome (p < 0.01) and provided independent prognostic information (multiple linear regression analysis, p < 0.05). Acute penumbral patterns were present in 14 of 26 patients. Most of these patients (9 of 14) had no MCA flow, whereas all nonpenumbral patients (PI ≤ DWI lesion) had MCA flow (p < 0.001). Penumbral-pattern patients with absent MCA flow had greater DWI lesion expansion (p < 0.05) and worse clinical outcome (Rankin Scale score, p < 0.05). Conclusions: Absent MCA flow on MRA predicts the presence of a presumed penumbral pattern on acute PI and DWI and worse stroke outcome. Combined MRA, PI, and DWI can identify individual patients at risk of ischemic core progression and the potential to respond to thrombolytic therapy beyond 3 hours.

Combined 1H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome

Background: The prognostic value of the biochemical changes seen with proton MR spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel localization. Methods: Nineteen patients had 36 1H MRS studies, 13 patients acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels from the infarct core. Outcome measures were final infarct volume and clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale). Results: Acute lactate/choline ratio correlated more strongly with clinical outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0.96; p < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of acute lactate/choline ratio with acute DWI lesion volume improved prediction of all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In subacute and chronic infarction, both lactate/choline and NAA/choline ratios continued to correlate with outcome (p < 0.05). At the chronic stage, persistent lactate/choline ratio elevation strongly correlated with outcome measures (r = 0.71 to 0.87). Conclusion: Lactate/choline ratio measured in the acute infarct core by 1H MRS improves the prediction of stroke outcome and provides prognostic information complementary to DWI. Lactate/choline ratio could be used as an additional marker to select patients for acute and chronic therapies.

Cerebral amyloid angiopathy related inflammation: three case reports and a review

Cerebral amyloid angiopathy related inflammation (CAA-I), previously described under various names, is a treatable encephalopathy usually occurring in older adults. Here, three patients are described with histopathologically confirmed CAA-I, and summarised data from the published literature are presented. CAA-I has a characteristic combination of clinical and radiological features. Definite diagnosis requires brain and leptomeningeal biopsy. A favourable response to immunosuppressive therapy is common and treatment without brain biopsy may be considered in selected patients. Diagnostic criteria for CAA-I are proposed.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch

Objective: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. Methods: EPITHET randomized patients 3–6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. Results: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6–9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6–6.2 mL, p < 0.001). Perfusion–diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. Conclusions: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion–diffusion mismatch.

Limbic encephalitis – a review

The clinical features of limbic encephalitis are diverse and early diagnosis of the disorder is frequently difficult. Four patients with limbic encephalitis are described. An antineuronal antibody was identified in three of these patients. Antibodies directed against voltage-gated potassium channels, the N-methyl-D-aspartate receptor and an unidentified neuropil antigen were each found in one patient. The fourth patient had multifocal paraneoplastic encephalitis associated with small cell lung cancer. The clinical and imaging findings associated with these antibodies and the other antineuronal antibodies described in patients with limbic encephalitis are reviewed. An approach to the diagnosis and management of limbic encephalitis is presented.

Cannabis, Ischemic Stroke, and Transient Ischemic Attack A Case-Control Study

Background and Purpose— There is a temporal relationship between cannabis use and stroke in case series and population-based studies. Methods— Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. Results— One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; &khgr;2: P=0.016) and tobacco smokers (88% versus 28%; &khgr;2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08–5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71–3.70). Conclusions— This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022

Improved Survival after Stroke: Is Admission to Hospital the Major Explanation? Trend Analyses of the Auckland Regional Community Stroke Studies

Background: There is uncertainty regarding the impact of changes in stroke care and natural history of stroke in the community. We examined factors responsible for trends in survival after stroke in a series of population-based studies. Methods: We used statistical models to assess temporal trends in 28-day and 1-year case fatality after first-ever stroke cases registered in 3 stroke incidence studies undertaken in Auckland, New Zealand, over uniform 12-month calendar periods in 1981–1982 (n = 1,030), 1991–1992 (1,305) and 2001–2002 (1,423). Cox proportional hazards regression was used to evaluate the significance of pre-defined ‘patient’, ‘disease’ and ‘service/care’ factors on these trends. Results: Overall, there was a 40% decline in 28-day case fatality after stroke over the study periods, from 32% (95% confidence interval, 29–35%) in 1981–1982 to 23% (21–25%) in 1991–1992 and then 19% (17–21%) in 2002–2003. Similar relative declines were seen in 1-year case fatality. In regression models, the trends were still significant after adjusting for patient and disease factors. However, further adjustment for care factors (higher hospital admission and neuroimaging) explained most of the improvement in survival. Conclusions: These data show significant downwards trends in case fatality after stroke in Auckland over 20 years, which can largely be attributed to improved stroke care associated with increases in hospital admission and brain imaging during the acute phase of the illness.

Bilateral Priming Accelerates Recovery of Upper Limb Function After Stroke A Randomized Controlled Trial

Background and Purpose— The ability to live independently after stroke depends on the recovery of upper limb function. We hypothesized that bilateral priming with active–passive movements before upper limb physiotherapy would promote rebalancing of corticomotor excitability and would accelerate upper limb recovery at the subacute stage. Methods— A single-center randomized controlled trial of bilateral priming was conducted with 57 patients randomized at the subacute stage after first-ever ischemic stroke. The PRIMED group made device-assisted mirror symmetrical bimanual movements before upper limb physiotherapy, every weekday for 4 weeks. The CONTROL group was given intermittent cutaneous electric stimulation of the paretic forearm before physiotherapy. Assessments were made at baseline, 6, 12, and 26 weeks. The primary end point was the proportion of patients who reached their plateau for upper limb function at 12 weeks, measured with the Action Research Arm Test. Results— Odds ratios indicated that PRIMED participants were 3× more likely than controls to reach their recovery plateau by 12 weeks. Intention-to-treat and per-protocol analyses showed a greater proportion of PRIMED participants achieved their plateau by 12 weeks (intention to treat, &khgr;2=4.25; P=0.039 and per protocol, &khgr;2=3.99; P=0.046). ANOVA of per-protocol data showed PRIMED participants had greater rebalancing of corticomotor excitability than controls at 12 and 26 weeks and interhemispheric inhibition at 26 weeks (all P<0.05). Conclusions— Bilateral priming accelerated recovery of upper limb function in the initial weeks after stroke. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ANZCTR1260900046822.