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Biomedical subjects

Martin S Dennis

Publications and source records attributed to Martin S Dennis.

At least 19 recordsLinked to original sources
PubMed2006

Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem cell Trial of recovery EnhanceMent after Stroke (STEMS) pilot randomized, controlled trial (ISRCTN 16784092).

BACKGROUND AND PURPOSE: Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34+ stem cells. METHODS: We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 microg/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34+ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. RESULTS: Thirty-six patients, whose mean+/-SD age was 76+/-8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 microg/kg) increased CD34+ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P=0.005). A dose-dependent rise in white cell count (P<0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. CONCLUSIONS: G-CSF is effective at mobilizing bone marrow CD34+ stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined.

Aged↗
PubMed2006

Abnormal breathing patterns in stroke: relationship with location of acute stroke lesion and prior cerebrovascular disease.

OBJECTIVE: To determine whether central periodic breathing (CPB) is associated with acute involvement of any particular part of the brain, or the extent of total damage in patients with acute stroke. METHODS: CPB was identified using portable monitoring equipment in patients with stroke on admission. A neuroradiologist classified acute stroke lesions and prior cerebrovascular disease on brain images. RESULTS: Among 134 patients with acute stroke, those with CPB were more likely to have a large acute stroke lesion in a cerebral hemisphere (p = 0.01) and more mass effect (p = 0.03). There was no association between CPB and severe prior cerebrovascular disease on imaging (p = 0.76). CONCLUSION: CPB is related to the acute (not old) lesions, particularly large acute cerebral hemispheric lesions with mass effect. A relationship between lesions in any discrete brain location (unilateral or bilateral) and CPB could not be shown.

Acute Disease↗
PubMed2006

Cerebral microbleeds are associated with lacunar stroke defined clinically and radiologically, independently of white matter lesions.

BACKGROUND AND PURPOSE: Associations among microbleeds, white matter lesions (WMLs), and small deep infarcts on imaging have been reported. Because many of these imaging infarcts were asymptomatic, the relationship of microbleeds to clinical lacunar stroke is unclear. An association between microbleeds and clinically defined lacunar stroke might suggest a common causal microangiopathy. METHODS: Patients with lacunar, partial anterior circulation or posterior circulation stroke syndromes and older healthy subjects underwent MRI. Microhemorrhages, infarcts, hemorrhages, and WMLs were coded blind to clinical details. A final clinicoradiologic stroke subtype diagnosis was assigned. RESULTS: Among 308 subjects (67 older healthy and 241 with stroke), 54 patients had microbleeds (17%). Microbleeds were twice as frequent in lacunar than cortical strokes (26% versus 13%, P=0.03) or healthy older subjects (9%) and associated with increasing WML scores (P<0.0001). Lacunar and cortical stroke subtypes and healthy older subjects had similar WML scores. CONCLUSIONS: Microbleeds are associated with lacunar stroke defined clinicoradiologically more than other stroke subtypes but not simply by association with WMLs. This suggests that microbleeds and lacunar stroke have a similar microvascular abnormality.

Aged↗
PubMed2006

Persistent infarct hyperintensity on diffusion-weighted imaging late after stroke indicates heterogeneous, delayed, infarct evolution.

BACKGROUND AND PURPOSE: Some infarcts have persistently hyperintense areas on diffusion-weighted MRI (DWI) even at 1 month after stroke, whereas others have become isointense to normal brain. We hypothesized that late DWI hyperintensity reflected different infarct evolution compared with areas that were isointense by 1 month. METHODS: We recruited patients prospectively with ischemic stroke, performed DWI and perfusion-weighted MRI (PWI) on admission, at 5 days, 14 days, and 1 month after stroke, and assessed functional outcome at 3 months (Rankin Scale). Patient characteristics and DWI/PWI values were compared for patients with or without "still hyperintense" infarct areas on 1-month DWI. RESULTS: Among 42 patients, 27 (64%) had "still hyperintense" infarct regions at 1 month, mostly in white matter. Patients with "still hyperintense" regions at 1 month had lower baseline apparent diffusion coefficient ratio (ADCr; mean+/-SD 0.76+/-0.12 versus 0.85+/-0.12; hyperintense versus isointense; P<0.05), prolonged reduction of ADCr (repeated-measures ANOVA; P<0.01), no difference in baseline perfusion but delayed normalization of mean transit time (P<0.05) and cerebral blood flow ratios (repeated measures ANOVA; P<0.05), initially more severe stroke, and worse 3-month outcome than patients whose lesions were isointense by 1 month. CONCLUSIONS: The late DWI lesion hyperintensity emphasizes the heterogeneity in temporal evolution of stroke injury and suggests ongoing "ischemia." Lower baseline ADCr precedes delayed perfusion normalization, suggesting that worse cell swelling impedes reperfusion. Further study is required to determine underlying mechanisms and any potential for subacute intervention to improve recovery.

Adult↗
PubMed2006

Distinguishing between stroke and mimic at the bedside: the brain attack study.

BACKGROUND AND PURPOSE: The bedside clinical assessment of the patient with suspected stroke has not been well studied. Improving clinical skills may accelerate patient progress through the emergency department. We aimed to determine the frequency and nature of stroke mimics and to identify the key clinical features that distinguish between stroke and mimic at the bedside. METHODS: Consecutive presentations to an urban teaching hospital with suspected stroke were recruited. A standard bedside clinical assessment was performed. The final diagnosis was determined by an expert panel, which had access to clinical features, brain imaging, and other tests. Univariate and multivariate analyses determined the bedside features that distinguished stroke from mimic. RESULTS: There were 350 presentations by 336 patients. The final diagnosis was stroke in 241 of 350 (69%) and mimic in 109 (31%). The mimics included 44 events labeled "possible stroke or TIA." Eight items independently predicted the diagnosis in patients presenting with brain attack: cognitive impairment and abnormal signs in other systems suggested a mimic, an exact time of onset, definite focal symptoms, abnormal vascular findings, presence of neurological signs, being able to lateralize the signs to the left or right side of the brain, and being able to determine a clinical stroke subclassification suggested a stroke. CONCLUSIONS: The bedside clinical assessment can be streamlined substantially. This has important implications for teaching less experienced clinicians how to assess the patient with suspected stroke.

Adolescent↗
PubMed2006

Interobserver agreement for the bedside clinical assessment of suspected stroke.

BACKGROUND AND PURPOSE: Stroke remains primarily a clinical diagnosis, with information obtained from history and examination determining further management. We aimed to measure inter-rater reliability for the clinical assessment of stroke, with emphasis on items of history, timing of symptom onset, and diagnosis of stroke or mimic. We explored reasons for poor reliability. METHODS: The study was based in an urban hospital with an acute stroke unit. Pairs of observers independently assessed suspected stroke patients. Findings from history, neurological examination, and the diagnosis of stroke or mimic, were recorded on a standard form. Reliability was measured by the kappa statistic. We assessed the impact of observer experience and confidence, time of assessment, and patient-related factors of age, confusion, and aphasia on inter-rater reliability. RESULTS: Ninety-eight patients were recruited. Most items of the history and the diagnosis of stroke were found to have moderate to good inter-rater reliability. There was agreement for the hour and minute of symptom onset in only 45% of cases. Observer experience and confidence improved reliability; patient-related factors of confusion and aphasia made the assessment more difficult. There was a trend for worse inter-rater reliability among patients assessed very early and very late after symptom onset. CONCLUSIONS: Clinicians should be aware that inter-rater reliability of the clinical assessment is affected by a variety of factors and is improved by experience and confidence. Our findings have implications for training of doctors who assess patients with suspected stroke and identifies the more reliable components of the clinical assessment.

Aged↗
PubMed2006

Central periodic breathing observed on hospital admission is associated with an adverse prognosis in conscious acute stroke patients.

BACKGROUND: Central periodic breathing (CPB) is common following acute stroke, but its prognostic significance is uncertain. We determined the frequency of CPB on admission with stroke and assessed whether it was related to outcome. METHODS: We measured arterial oxygen saturation (SaO2), chest wall movements and nasal airflow continually with portable monitoring equipment in a large cohort of acute stroke patients, from arrival at hospital through acute assessment to reaching the ward. Baseline neurological examination and 3-month outcome (modified Rankin scale, MRS) were assessed blind to recordings. CPB was defined as cyclical rises and falls in ventilation, with intermittent reduced respiratory airflow or total apnoea. RESULTS: CPB was common in acute stroke (33/138, 24%), but was poorly recognised by clinical staff. Patients with CPB were more likely to have a total anterior circulation syndrome and higher National Institutes of Health Stroke Scale scores than those without (both p<0.01). Patients with CPB had significantly higher median SaO2 than those without (p<0.01), unrelated to whether they received oxygen or not. At 3-month follow-up: 91% of patients with CPB were dead or dependent (MRS>or=3) compared with 53% of those without (OR 8.8; 95% CI 2.5-30.5); the association remained statistically significant after adjusting for covariates (OR 5.9; 95% CI 1.4-25.4). CONCLUSION: CPB is independently associated with poor outcome after stroke, but is not by association with hypoxia. Further work is required to identify causes, effects and interventions that might improve effects of CPB.

Aged↗
PubMed2006

Measurement of brain temperature with magnetic resonance spectroscopy in acute ischemic stroke.

OBJECTIVE: Pyrexia is associated with poor outcome after stroke, but the temperature changes in the brain after stroke are poorly understood. We used magnetic resonance spectroscopic imaging (water-to-N-acetylaspartate frequency shift) to measure cerebral temperature noninvasively in stroke patients. METHODS: We performed magnetic resonance diffusion, perfusion (diffusion- and perfusion-weighted imaging), and magnetic resonance spectroscopic imaging, compared temperatures in tissues as defined by the diffusion-weighted imaging appearance (definitely abnormal, possibly abnormal and immediately adjacent normal-appearing brain, and normal brain), and tested associations with lesion and patient characteristics. RESULTS: Among 40 patients, temperature was higher in possibly abnormal (37.63 degrees C) than in definitely abnormal tissue (37.30 degrees C; p < 0.001) or in normal-appearing brain (ipsilateral, 37.16 degrees C; contralateral, 37.22 degrees C; both p < 0.001). Ischemic lesion temperature increased before normal brain temperature. Higher temperatures occurred in lesions that were large, had diffusion/perfusion-weighted imaging mismatch, had reduced cerebral blood flow, and in clinically severe strokes. Only 1 of 25 patients with ischemic lesion temperature greater than 37.5 degrees C was pyrexial. INTERPRETATION: Temperature is elevated in acutely ischemic brain. More work is required to determine whether raised temperature results from ischemic metabolic reactions, impaired heat exchange from reduced cerebral blood flow, or early inflammatory cell activity (or a combination of these), but magnetic resonance spectroscopic imaging could be used in studies of temperature after brain injury and to monitor interventions.

Aged↗
PubMed2005

Hypoxaemia in acute stroke is frequent and worsens outcome.

BACKGROUND: Hypoxaemia in the acute phase of stroke might damage the ischaemic penumbra and worsen clinical outcome. We determined the frequency of hypoxaemia on admission with stroke and assessed whether it was related to outcome. METHODS: We measured arterial oxygen saturation (SaO2) and breathing effort with portable monitoring equipment in a large cohort of acute stroke patients, continually from arrival at hospital, during interdepartment transfer, in imaging and on the ward. Patients received best medical care according to current guidelines. Baseline neurological examination and 3-month outcome (Modified Rankin Scale) were assessed blind to other data. Hypoxaemia was defined as SaO2 <90% for >or=10% of each assessment stage. RESULTS: Mean SaO2 was lowest during transfers (p < 0.01), but hypoxaemia was common in all assessment stages. Patients with hypoxaemia (30/153, 20%) were more likely to have a pre-existing respiratory disease on admission than those without hypoxaemia (p < 0.04). More patients with hypoxaemia (40%) died than those without hypoxaemia (20%) (hazard ratio, 2.0; 95% CI, 1.0-4.1), though after adjusting for National Institute of Health Stroke Scale and age this association was not statistically significant (hazard ratio, 1.5; 95% CI, 0.7-3.1). There were similar numbers of dependent survivors in both groups. CONCLUSION: Hypoxaemia during acute stroke assessment was associated with increased risk of death. Although SaO2 is lower during transfers, hypoxaemia occurs in all stages of the admission process. Further research is necessary to determine whether strategies to avoid hypoxaemia during acute assessment improve stroke survival.

Aged↗
PubMed2005

Study of the relationship between social deprivation and outcome after stroke.

BACKGROUND AND PURPOSE: Although the incidence and mortality of stroke are known to be inversely related to socioeconomic status (SES), the relationship between SES and recovery after stroke has been little-studied. This study has investigated the relationship between SES and case fatality, "death or dependency," and "death or institutional care" at 6 months after stroke. METHODS: Patients with acute stroke (n=2709) were identified using routine hospital discharge data and SES was measured using Carstairs scores (an ecological index of social deprivation). Case mix and treatment data were collected by medical chart review, case fatality by record linkage, and functional status and place of residence by questionnaire. Logistic regression was used to adjust the association of social deprivation and outcome for case mix and selected treatment variables. RESULTS: With increasing social deprivation, patients were younger, more likely to live alone, and, on admission, more likely to need help to walk. Social deprivation was not associated with case fatality or with "death or institutional care" in any analysis. However, patients residing in the most deprived areas (deprivation categories 6 and 7) were significantly more likely to be dead or dependent than patients from more affluent areas. This association was weakened but remained after adjusting for case mix and treatment variables. CONCLUSIONS: These findings contribute to growing evidence of an inverse social gradient in disability after stroke. Institutionalization, as a proxy for functional outcome, may not reflect this fact. A marked social gradient in case fatality after stroke seems unlikely.

Aged↗
PubMed2003

Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case-control study in patients with transient ischemic attacks.

BACKGROUND AND PURPOSE: The evidence that obstructive sleep apnea/hypopnea (OSAH) is a risk factor for ischemic cerebrovascular disease is inconclusive. We explored this relationship in transient ischemic attack (TIA) patients because they are less likely than stroke patients to have OSAH as a consequence of cerebrovascular disease. METHODS: We performed a case-control study among 86 patients with TIA from a hospital neurovascular clinic, matched for age (+/-5 years) and sex with controls from the referring local family practice registers. RESULTS: Forty-nine of the 86 matched pairs were male and the body mass index was similar among cases and controls. The primary outcome measure, the apnea/hypopnea index [AHI=number of (apneas+hypopneas)/h slept, measured during overnight polysomnography and scored blind to case-control status], was the same for cases and controls (21/hour). However, the median number of 4% desaturations during sleep was slightly greater in the cases (12/hour) than controls (6/hour, P=0.04). There were the expected associations between TIA and higher fibrinogen levels (TIA 3.3, control 3.0 g/L, P=0.01), previous myocardial infarction (TIA 22, control 6%, P=0.007), a history of ever smoking (TIA 71, control 54%, P=0.01), hypertension (TIA 51, control 21%, P=0.001), and raised cholesterol (TIA 27, control 10%, P=0.01), with a weak trend for diabetes mellitus (TIA 10, control 6%, P=0.4). CONCLUSIONS: OSAH does not appear to be strongly associated with TIAs.

Aged↗
PubMed2003

Outcome after brain haemorrhage.

Between 10 and 20% of strokes are due to intracerebral haemorrhage. The 1-month case fatality is about 42% in unselected cohorts. This relatively low incidence (compared with ischaemic stroke) and high early case fatality means that relatively few patients are available for long-term follow-up and therefore the available data on prognosis are imprecise. Moreover, improvements in diagnostic methods, such as the introduction of gradient echo MRI, which is very sensitive to intracerebral haemorrhage, are altering the types of patients being entered into studies of prognosis. Despite these methodological difficulties, it does appear that the overall prognosis with respect to survival and residual disability is similar to that for ischaemic stroke of equivalent clinical severity. Greater age and stroke severity, whether graded by neurological score or extent of haemorrhage on imaging, are both associated with increased case fatality and poorer functional outcomes. There is no definite evidence of differential recovery between ischaemic and haemorrhagic stroke. Epileptic seizures occur more commonly after haemorrhagic stroke (about 8 per 100 patient-years) compared with ischaemic stroke and more commonly in lobar rather than basal ganglia haemorrhage. There is no reliable evidence to indicate that the risk of recurrent stroke after haemorrhage differs from that after ischaemic stroke. However, strokes due to haemorrhage, like those due to infarction, are heterogeneous not only in terms of severity but also in their causes. The causes (e.g. amyloid angiopathy, hypertension, coagulation deficits) are likely to influence the risk of subsequent stroke. Pooling of data from community-based studies of haemorrhagic stroke that have used consistent definitions and methods represents the only feasible way to obtain more precise data on prognosis after intracerebral haemorrhage.

Humans↗
PubMed2002

Extensive haemorrhagic transformation of infarct: might it be an important cause of primary intracerebral haemorrhage?

Data from prior studies using serial imaging and post mortem data support the possibility that at least some cases of apparent primary intracerebral haemorrhage are due to early haemorrhagic transformation of infarct. If some primary intracerabral haemorrhage is actually early haemorrhagic transformation of infarct, then secondary stroke prevention for ischaemic stroke might be appropriate and so future studies should obtain data to determine the frequency of early major haemorrhagic transformation of infarct.

Aged↗
PubMed2002

Relationship between absolute mean cerebral transit time and absolute mean flow velocity on transcranial Doppler ultrasound after ischemic stroke.

BACKGROUND AND PURPOSE: Previous studies of transcranial Doppler (TCD) sonography in acute stroke have used the relative difference between the symptomatic and asymptomatic arteries to assess arterial occlusion. However, a simple measure of absolute mean flow velocity might provide a direct assessment of "perfusion reserve" in acute ischemic stroke. METHODS: In a prospective study, 62 patients with ischemic stroke had TCD and a mean cerebral transit time examination within 48 hours of stroke. Absolute intracranial arterial mean flow velocities were correlated with the corresponding absolute mean transit times. RESULTS: The authors found a significant correlation between middle cerebral artery (MCA) mean flow velocity and transit time in the symptomatic (Spearman rank correlation coefficient [rho] = -0.65, P < .01) but not in the asymptomatic (rho = -0.04, P = ns) MCA territory. Equations relating absolute mean flow velocity to absolute transit time were derived. CONCLUSION: The findings suggest that in the normal hemisphere (with intact autoregulation on the horizontal portion of the autoregulation curve), flow velocity and transit time are not closely related to each other, but in the symptomatic hemisphere (on the downward slope of the autoregulation curve), flow velocity is directly proportional to the transit time and, therefore, to its inverse, perfusion reserve. The use of absolute mean flow velocity values on TCD should be further explored as a simple way of assessing "perfusion" in acute ischemic stroke.

Blood Flow Velocity↗