Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients.

BACKGROUND: Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia. METHODS: All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated. RESULTS: A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%. CONCLUSIONS: Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias.

Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588(®) (CBM 588(®)), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, ß, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin.

AIMS: We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. METHODS: For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. RESULTS: Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. CONCLUSIONS: Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations.

The outcome of tibial diaphyseal fractures in the elderly.

We describe the outcome of tibial diaphyseal fractures in the elderly (≥ 65 years of age). We prospectively followed 233 fractures in 225 elderly patients over a minimum ten-year period. Demographic and descriptive data were acquired from a prospective trauma database. Mortality status was obtained from the General Register Office database for Scotland. Diaphyseal fractures of the tibia in the elderly occurred predominantly in women (73%) and after a fall (61%). During the study period the incidence of these fractures decreased, nearly halving in number. The 120-day and one-year unadjusted mortality rates were 17% and 27%, respectively, and were significantly greater in patients with an open fracture (p < 0.001). The overall standardised mortality ratio (SMR) was significantly increased (SMR 4.4, p < 0.001) relative to the population at risk, and was greatest for elderly women (SMR 8.1, p < 0.001). These frailer patients had more severe injuries, with an increased rate of open fractures (30%), and suffered a greater rate of nonunion (10%). Tibial diaphyseal fractures in the elderly are most common in women after a fall, are more likely to be open than in the rest of the population, and are associated with a high incidence of nonunion and mortality.

High frequency of missense mutations in glycogen storage disease type VI.

Deficiency of liver glycogen phosphorylase in glycogen storage disease (GSD) type VI results in a reduced ability to mobilize glucose from glycogen. Six mutations of the PYGL gene, which encodes the liver isoform of the enzyme, have been identified in the literature. We have characterized eight patients from seven families with GSD type VI and identified 11 novel PYGL gene defects. The majority of the mutations were missense, resulting in the substitution of highly conserved residues. These could be grouped into those that were predicted to affect substrate binding (p.V456M, p.E673K, p.S675L, p.S675T), pyridoxal phosphate binding (p.R491C, p.K681T), or activation of glycogen phosphorylase (p.Q13P) or that had an unknown effect (p.N632I and p.D634H). Two mutations were predicted to result in null alleles, p.R399X and [c.1964_1969inv6;c.1969+1_+4delGTAC]. Only 7 of the 23 (30%) reported PYGL alleles carry nonsense, splice site or frameshift mutations compared to 68-80% of affected alleles of the highly homologous muscle glycogen phosphorylase gene, PYGM, that underlie McArdle disease. There was heterogeneity in the clinical symptoms observed in affected individuals. These varied from hepatomegaly and subclinical hypoglycaemia, to severe hepatomegaly with recurrent severe hypoglycaemia and postprandial lactic acidosis. We conclude that deficiency of liver glycogen phosphorylase is predominantly the result of missense mutations affecting enzyme activity. There are no common mutations and the severity of clinical symptoms varies significantly.

Physical activity and white matter lesion progression: assessment using MRI.

We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.

Perfusion-weighted MRI as a marker of response to treatment in acute and subacute stroke.

We carried out baseline and short-term follow-up MRI, including perfusion-weighted imaging (PWI) and tests of neurologic and cognitive function on 15 consecutive patients with large-vessel ischemic stroke who showed a persistent large perfusion-diffusion mismatch at enrollment up to seven days after the onset of symptoms. Of these, ten underwent induced blood pressure elevation with phenylephrine and oral medications (in eight) or intravenous fluids (in two) with the goal of improving perfusion; five had no such treatment. Significant functional improvement was defined by a reduction of 3 or more points on the NIH stroke scale (NIHSS). Significant improvement in perfusion was defined by a reduction in the volume of hypoperfused brain by 30 cc on PWI using time-to-peak (TTP) maps, without enlargement of the infarct. There was a strong, statistically significant association between improved function and improved perfusion: six (75%) of eight patients who improved in function, but none of the seven who did not, showed a reduction in volume of hypoperfused brain. All six patients who met the perfusion goal, and only two (22%) of nine who did not showed significant functional improvement (Fisher's exact: P < 0.01). There were no differences between patients who improved functionally and those who did not with respect to age, initial volume of abnormality on DWI or PWI, initial NIHSS, or changes on DWI. These findings indicate that reduction in volume of hypoperfused brain on PWI is a marker of response to treatment to improve perfusion even in subacute stroke and that partial reperfusion of regions of salvageable but dysfunctional tissue is a mechanism of improved function associated with induced blood pressure elevation.

A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.

BACKGROUND: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. METHODS: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation ('treated' patients, n = 9) or conventional management ('untreated' patients, n = 6). RESULTS: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6-8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. CONCLUSION: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

MRI and proton MRSI in women heterozygous for X-linked adrenoleukodystrophy.

OBJECTIVE: To utilize neuroimaging procedures to assess the extent of cerebral involvement in female subjects heterozygous for X-linked adrenoleukodystrophy (X-ALD). METHODS: Brain MRI studies were performed in 76 female subjects heterozygous for X-ALD (mean age 43 years, range 8 to 75 years). Sixty-five had clinical evidence of spinal cord involvement resembling that in males with adrenomyeloneuropathy (AMN), two had clinical evidence of cerebral involvement, and nine showed no neurologic abnormality. Readers blinded to clinical findings further analyzed abnormal MRI studies. In eight women whose MRI results were normal, four-slice long echo time MRS imaging (MRSI) studies were performed and compared to those of eight age-matched controls. RESULTS: MRI results were normal in 65 subjects and abnormal in 11. In eight of the latter group, the MRI changes were judged to be due to causes other than X-ALD. Lesions were attributed to X-ALD in the remaining three. Two of these patients had lesions that resembled those in male patients with cerebral X-ALD. In one patient with a mild AMN-like syndrome, brain MRI abnormalities were confined to the corticospinal tract. When compared to those of controls, MRSI studies in eight female patients with normal results on brain MRI showed a significant reduction of N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in the internal capsule and corticospinal projection fibers. The N-acetylaspartate/choline ratio was significantly reduced in the parieto-occipital white matter and the choline/creatine ratio was significantly increased in the frontal white matter. CONCLUSION: Brain involvement demonstrable by MRI is rare in female subjects heterozygous for X-ALD, including those who have clinical evidence of spinal cord involvement. Nevertheless, N-acetylaspartate levels are reduced in the corticospinal projection fibers in female subjects with normal results on MRI, suggesting axonal dysfunction.

Subcortical aphasia and neglect in acute stroke: the role of cortical hypoperfusion.

We have hypothesized that most cases of aphasia or hemispatial neglect due to acute, subcortical infarct can be accounted for by concurrent cortical hypoperfusion. To test this hypothesis, we demonstrate: (i) that pure subcortical infarctions are associated with cortical hypoperfusion in subjects with aphasia/neglect; (ii) that reversal of cortical hypoperfusion is associated with resolution of the aphasia; and (iii) that aphasia/neglect strongly predicts cortical ischaemia and/or hypoperfusion. We prospectively evaluated a consecutive series of 115 patients who presented within 24 h of onset or progression of stroke symptoms, with MRI sequences including diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI), and detailed testing for aphasia or hemispatial neglect. The association between aphasia or neglect and cortical infarct (or dense ischaemia) on DWI and cortical hypoperfusion indicated by PWI, was evaluated with chi-squared analyses. Fisher exact tests were used for analyses with small samples. Cases of DWI lesion restricted to subcortical white matter and/or grey matter structures (n = 44) were examined for the presence of aphasia or neglect, and for the presence of cortical hypoperfusion. In addition, subjects who received intervention to restore perfusion were evaluated with DWI, PWI, and cognitive tests before and after intervention. Finally, the positive predictive value of the cognitive deficits for identifying cortical abnormalities on DWI and PWI were calculated from all patients. Of the subjects with only subcortical lesions on DWI in this study (n = 44), all those who had aphasia or neglect showed concurrent cortical hypoperfusion. Among the patients who received intervention that successfully restored cortical perfusion, 100% (six out of six) showed immediate resolution of aphasia. In the 115 patients, aphasia and neglect were much more strongly associated with cortical hypoperfusion (chi(2) = 57.3 for aphasia; chi(2) = 28.7 for neglect; d.f. = 1; P < 0.000001 for each), than with cortical infarct/ischaemia on DWI (chi(2) = 8.5 for aphasia; chi(2) = 9.7 for neglect; d.f. = 1; P < 0.005 for each). Aphasia showed a much higher positive predictive value for cortical abnormality on PWI (95%) than on DWI (62%), as did neglect (100% positive predictive value for PWI versus 74% for DWI). From these data we conclude that aphasia and neglect due to acute subcortical stroke can be largely explained by cortical hypoperfusion.

Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke.

Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernicke's area, we tested the hypothesis that the severity of word comprehension impairment was correlated with the magnitude of delay in perfusion of Wernicke's area on magnetic resonance perfusion-weighted imaging. Eighty patients were prospectively studied within 24 hours of onset or progression of acute left hemisphere stroke symptoms, with diffusion-weighted imaging, perfusion-weighted imaging, and detailed language tests. For 50 patients without infarct in Wernicke's area, we found a strong Pearson correlation between the rate of errors on a word comprehension test and the mean number of seconds of delay in time-to-peak concentration of contrast in Wernicke's area, relative to the homologous region on the right. These results add further evidence for the crucial role of Wernicke's area (Brodmann's area 22) in word comprehension and indicate that the magnitude of delay on PWI may be a gross indicator of tissue dysfunction.

Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly. OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors. METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts. RESULTS: Approximately 28% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes). CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

Vascular compression by a ventricular shunt catheter: clinical value of volume-rendered CT angiography.

One of the strongest advantages of CT angiography (CTA) lies in its unique ability to display simultaneously the anatomy of the vascular system and the topographic relationships existing between the vessels and the neighboring structures. The case we report, a 76-year-old man who underwent an intraventricular shunt placement complicated by a stroke, shows how this topographic assessment also provides important diagnostic information when vascular lesions resulting from an extrinsic compression mechanism are suspected.

Interaction of phytochromes A and B in the control of de-etiolation and flowering in pea.

The interactions of phytochrome A (phyA) and phytochrome B (phyB) in the photocontrol of vegetative and reproductive development in pea have been investigated using null mutants for each phytochrome. White-light-grown phyA phyB double mutant plants show severely impaired de-etiolation both at the seedling stage and later in development, with a reduced rate of leaf production and swollen, twisted internodes, and enlarged cells in all stem tissues. PhyA and phyB act in a highly redundant manner to control de-etiolation under continuous, high-irradiance red light. The phyA phyB double mutant shows no significant residual phytochrome responses for either de-etiolation or shade-avoidance, but undergoes partial de-etiolation in blue light. PhyB is shown to inhibit flowering under both long and short photoperiods and this inhibition is required for expression of the promotive effect of phyA. PhyA is solely responsible for the promotion of flowering by night-breaks with white light, whereas phyB appears to play a major role in detection of light quality in end-of-day light treatments, night breaks and day extensions. Finally, the inhibitory effect of phyB is not graft-transmissible, suggesting that phyB acts in a different manner and after phyA in the control of flower induction.

Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients with neurologic complications after cardiac surgery.

BACKGROUND: Neurologic complications after cardiac surgery include stroke, encephalopathy, and persistent cognitive impairments. More precise neuroimaging of patients with these complications may lead to a better understanding of the etiology and treatment of these disorders. OBJECTIVE: To study the pattern of ischemic changes on diffusion- and perfusion-weighted magnetic resonance imaging (DWI, and MRPI, respectively) in patients with neurologic complications after cardiac surgery. METHODS: All records were reviewed of our patients undergoing cardiac surgery in the previous year who also underwent postoperative DWI or MRPI. Neurologic symptoms, vascular studies, and the pattern of ischemic changes were recorded. Acute ischemic lesions were classified as having a territorial, watershed, or lacunar pattern of infarction. Patients with multiple territorial infarcts in differing vascular distributions that were not explained by occlusive vascular lesions were classified as having multiple emboli. RESULTS: Fourteen patients underwent DWI and 4 underwent MRPI. Acute infarcts were found in 10 of 14 patients by DWI as compared with 5 of 12 patients by computed tomography. Eight patients presented with encephalopathy (associated with focal neurologic deficits in 4), 4 with focal deficits alone, and 2 with either fluctuating symptoms or transient ischemic attacks. Among patients with encephalopathy, 7 of 8 had patterns of infarction suggestive of multiple emboli, including 3 of 4 patients with no focal neurologic deficits. Several patients had combined watershed and multiple embolic patterns of ischemia. Findings of MRPI studies were abnormal in 2 of 4 patients, showing diffusion-perfusion mismatch; both patients had either fluctuating deficits or transient ischemic attacks, and their conditions improved with blood pressure manipulation. CONCLUSIONS: In patients with neurologic symptoms after cardiac surgery, DWI is more sensitive to ischemic change than computed tomographic scanning and can demonstrate patterns of infarction that may help us understand etiology. The most common pattern was multiple embolic infarcts. Preliminary experience with MRPI suggests that some patients have persistent diffusion-perfusion mismatch after surgery and may benefit from therapeutic intervention.

Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study.

OBJECTIVE: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis. SUBJECTS AND METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations. RESULTS: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected. CONCLUSIONS: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.

Restoring blood pressure reperfused Wernicke's area and improved language.

Longitudinal clinical and imaging data from a patient who sustained a left frontal-temporal stroke with hypoperfusion of the adjacent Wernicke's area are reported. His language deficits were partially ameliorated by pharmacologically increasing his blood pressure, and were exacerbated when blood pressure dropped. There was a striking temporal and statistical correlation between mean arterial pressure and language accuracy. MR perfusion imaging showed that language gains were accompanied by improved perfusion of Wernicke's area when mean arterial pressure was increased.