Biomedical subjects

J M Wardlaw

Publications and source records attributed to J M Wardlaw.

At least 19 recordsLinked to original sources

PubMed2004

What is the best imaging strategy for acute stroke?

OBJECTIVES: To determine the cost-effectiveness of computed tomographic (CT) scanning after acute stroke. To assess the contribution of brain imaging to the diagnosis and management of stroke, and to estimate the costs, benefits and risks of different imaging strategies in order to provide data to inform national and local policy on the use of brain imaging in stroke. DESIGN: A decision-analysis model was developed to represent the pathway of care in acute stroke using 'scan all patients within 48 hours' as the comparator against which to cost 12 alternative scan strategies. SETTING: Hospitals in Scotland. PARTICIPANTS: Subjects were patients admitted to hospital with a first stroke and those managed as outpatients. INTERVENTIONS: The effect on functional outcome after ischaemic or haemorrhagic stroke, tumours or infections, of correctly administered antithrombotic or other treatment; of time to scan and stroke severity on diagnosis by CT or MRI; on management, including length of stay, functional outcome, and quality-adjusted life years (QALYs), of the diagnostic information provided by CT scanning; the cost-effectiveness (cost versus QALYs) of different strategies for use of CT after acute stroke. MAIN OUTCOME MEASURES: Death and functional outcome at long-term follow-up; accuracy of CT and MRI; cost of CT scanning by time of day and week; effect of CT diagnosis on change in health outcome, length of stay in hospital and QALYs; cost-effectiveness of various scanning strategies. RESULTS: CT is very sensitive and specific for haemorrhage within the first 8 days of stroke only. Suboptimal scanning used in epidemiology studies suggests that the frequency of primary intracerebral haemorrhage (PICH) has been underestimated. Aspirin increases the risk of PICH. There were no reliable data on functional outcome or on the effect of antithrombotic treatment given long term after PICH. In 60% of patients with recurrent stroke after PICH, the cause is another PICH and mortality is high among PICH patients. A specific MR sequence (gradient echo) is required to identify prior PICH reliably. CT scanners were distributed unevenly in Scotland, 65% provided CT scanning within 48 hours of stroke, and 100% within 7 days for hospital-admitted patients, but access out of hours was very variable, and for outpatients was poor. The average cost of a CT brain scan for stroke was pounds 30.23 to pounds 89.56 in normal working hours and pounds 55.05 to pounds 173.46 out of hours. Average length of stay was greatest for severe strokes and those who survived in a dependent state. For a cohort of 1000 patients aged 70-74 years, the policy 'scan all strokes within 48 hours', cost pounds 10,279,728 and achieved 1982.3 QALYS. The most cost-effective strategy was 'scan all immediately' (pounds 9,993,676 and 1982.4 QALYS). The least cost-effective was to 'scan patients on anticoagulants, in a life-threatening condition immediately and the rest within 14 days'. CONCLUSIONS: In general, strategies in which most patients were scanned immediately cost least and achieved the most QALYs, as the cost of providing CT (even out of hours) was less than the cost of inpatient care. Increasing independent survival by even a small proportion through early use of aspirin in the majority with ischaemic stroke, avoiding aspirin in those with haemorrhagic stroke, and appropriate early management of those who have not had a stroke, reduced costs and increased QALYs.

Aged↗

PubMed2003

Thrombolytic therapy with recombinant tissue plasminogen activator for acute ischemic stroke: where do we go from here? A cumulative meta-analysis.

BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA; Actilyse) is not as widely used in clinical practice as it could be. Have new data since 1995 strengthened the evidence sufficiently to justify more widespread use of rtPA? METHODS: We performed a sequential year-to-year cumulative meta-analysis of randomized controlled trials of rtPA in acute ischemic stroke. RESULTS: Although the amount of data has doubled since 1995, effect estimates for key outcomes remain imprecise, and significant between-trial heterogeneity persists. In the most recent analysis, rtPA up to 6 hours after stroke yielded 55 fewer dead or dependent people per 1000 treated (95% CI, 18 to 92) despite some risk (nonsignificant excess of 19 deaths per 1000 patients treated; 95% CI, 6 fewer to 48 more). Severity of stroke, patient age, and aspirin use were possible sources of heterogeneity. CONCLUSIONS: Despite doubling of the data since 1995, the magnitude of risks and benefits with rtPA remains imprecise. This gap in knowledge may be hindering clinical use of rtPA and can be filled only by new trials designed to address these specific issues.

Acute Disease↗

PubMed2003

Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?

BACKGROUND: The pathogenesis of and relationship between small deep (lacunar) infarcts, cerebral white matter disease (leukoaraiosis or white matter hyperintensities), and progressive cognitive impairment or dementia are much debated. SUMMARY OF COMMENT: We hypothesize that cerebral small-vessel endothelial (ie, blood-brain barrier) dysfunction, with leakage of plasma components into the vessel wall and surrounding brain tissue leading to neuronal damage, may contribute to the development of 3 overlapping and disabling cerebrovascular conditions: lacunar stroke, leukoaraiosis, and dementia. This hypothesis could explain the link between ischemic cerebral small-vessel disease and several apparently clinically distinct dementia syndromes. This hypothesis is supported by pathological, epidemiological, and experimental studies in lacunar stroke and leukoaraiosis and observations on the blood-brain barrier with MRI. We suspect that the potential significance of blood-brain barrier failure as a pathogenetic step linking vascular disease with common, disabling brain diseases of insidious onset has been overlooked. For example, lipohyalinosis, which has a pathological appearance of uncertain origin and is possibly responsible for some discrete lacunar infarcts, may be one end of a clinical spectrum of illness manifested by blood-brain barrier failure. CONCLUSIONS: Proof that blood-brain barrier failure is key to these conditions could provide a target for new treatments to reduce the effects of vascular disease on the brain and prevent cognitive decline and dementia.

Aging↗

PubMed2003

The impact of delays in computed tomography of the brain on the accuracy of diagnosis and subsequent management in patients with minor stroke.

OBJECTIVES: To determine the proportion of haemorrhagic strokes misdiagnosed as infarcts on computed tomography (CT) in patients with mild stroke, and the implications for health care. METHODS: Patients with mild stroke presenting as inpatients or outpatients four or more days after stroke to our stroke service (catchment population 500 000) were recruited prospectively. They underwent detailed clinical examination and brain imaging with CT and magnetic resonance imaging (MRI) on the day of presentation. CT and MR images were examined independently to identify infarct, primary intracerebral haemorrhage, haemorrhagic transformation, or non-vascular lesion. RESULTS: In 228 patients with mild stroke (median time from stroke to scan 20 days), primary intracerebral haemorrhage was identified by CT in two patients (0.9%; 95% confidence interval (CI), 0.1% to 3.1%) and MRI in eight (3.5%; 1.5% to 6.8%). Haemorrhagic transformation was identified by CT in three patients (1.3%; 0.1% to 5.6%) and MRI in 15 (6.6%; 3.7% to 10.6%). The earliest time primary intracerebral haemorrhage was not identified on CT was 11 days. CONCLUSIONS: CT failed to identify 75% of primary intracerebral haemorrhages, equivalent to 24 patients per 1000 (95% CI, 14 to 37) with mild strokes. To detect haemorrhages reliably, CT would need to have been performed within about eight days. Rapid access to neurovascular clinics with same day CT brain imaging is required to avoid inappropriate secondary prevention. Increased public awareness of the need to seek urgent medical attention after stroke should be encouraged. MRI should be considered in late presenting patients.

Adult↗

PubMed2003

Diffuse brain oedema in idiopathic intracranial hypertension: a quantitative magnetic resonance imaging study.

OBJECTIVES: To investigate the hypothesis that idiopathic intracranial hypertension is associated with diffuse brain oedema, using quantitative magnetic resonance imaging. METHODS: Values for the mean diffusivity of water ( ) and the proton longitudinal relaxation time (T1) were measured for various brain regions in 10 patients with idiopathic intracranial hypertension and 10 age, sex, and weight matched controls. RESULTS: No significant differences in and T1 values were found between patient and control groups in any of the brain regions investigated. CONCLUSIONS: The results suggest that idiopathic intracranial hypertension is not associated with abnormalities of convective transependymal water flow leading to diffuse brain oedema.

Adolescent↗

PubMed2003

Visible infarction on computed tomography is an independent predictor of poor functional outcome after stroke, and not of haemorrhagic transformation.

OBJECTIVES: To examine a very large dataset to provide a robust answer to the question of whether visible infarction on computed tomography was (a) an independent predictor of functional outcome at all times up to 48 hours after stroke, and (b) independently associated with haemorrhagic transformation, with or without antithrombotic treatment. METHODS: The study assessed associations between visible infarction, time to randomisation, baseline neurological deficit, stroke syndrome, allocated aspirin or heparin treatment, recurrent haemorrhagic stroke, early death and six month functional outcome in the International Stroke Trial. RESULTS: Of 12 550 patients, 6267 (50%) had visible infarction up to 48 hours after stroke. The prevalence of visible infarction increased with increasing time from onset and extent of the stroke syndrome. Visible infarction was independently associated with increased death within 14 days (odds ratio (OR) 1.17, 95% CI 1.02 to 1.35), and of death or dependency at six months (OR 1.42, 95% CI 1.31 to 1.55), an absolute increase of 13%, or 130 per 1000 more dead or dependent patients with visible infarction than without it. There was no significant independent relation between visible infarction and fatal or non-fatal haemorrhagic transformation, or interaction between visible infarction and aspirin or heparin treatment allocation with six month functional outcome. CONCLUSIONS: Visible infarction on computed tomography up to 48 hours after stroke is an independent adverse prognostic sign.

Aged↗

PubMed2003

Unruptured intracranial aneurysms.

Between 3.6 and 6% of the population harbour an unruptured intracranial aneurysm. Risk of rupture is related to aneurysm site and size and whether or not the patient has already had a subarachnoid haemorrhage (SAH) from another aneurysm. In ISUIA 2, the rupture rate for anterior circulation aneurysms<7mm was 0% per year in patients with no prior SAH, and 0.3% per year in patients with previous SAH; 7-12mm aneurysms, 0.5% per year (both groups); 13-24mm aneurysms, 3% per year; and giant aneurysms 8% per year. Rupture rate for posterior circulation aneurysms is higher at all sizes:<7mm was 0.5% per year in subjects with no prior SAH, 0.7% in those with prior SAH; 7-12mm, 3% per year; 13-24mm, 3.7% per year; and giant aneurysms, 10% per year. Non-invasive tests like contrast enhanced magnetic resonance angiography (MRA) and multislice computed tomographic angiography (CTA) are alternatives to intra-arterial digital subtraction angiography (IADSA) to detect aneurysms. Although these are promising techniques, the quality of data testing their accuracy remains limited and single slice CTA and time-of-flight MRA are poorer at detecting aneurysms<5mm diameter, which account for up to 1/3 of unruptured aneurysms. For ruptured aneurysms, the only large scale randomised controlled trial comparing surgical and endovascular treatment (ISAT) by coiling, resulted in an absolute 8.8% reduction (updated figure as of June 2003 for 1888 patients) in death or dependency at 1 year compared with surgical clipping. For unruptured aneurysms, the best available data so far comparing coiling and clipping is from the prospective (but non-randomised) arm of ISUIA. Elective surgical clipping had combined morbidity and mortality at 1 year of 12.2% versus 9.5% for coiling, although the groups were not matched with more high risk patients in the endovascular treatment cohort. Nevertheless these data are encouraging for future randomised trials of elective coiling versus clipping for asymptomatic aneurysms, in particular as the unproven long-term durability of coiling treatment and the fact that complete aneurysm occlusion is not always achieved remain obstacles to its wider use in unruptured aneurysms. There is an increased risk of SAH in relatives of patients with SAH (highest in those with two or more first degree relatives affected), but most SAH is sporadic and therefore the balance of available evidence indicates that mass screening for aneurysms is not cost effective. There may be a limited role for investigation of high-risk subgroups and ideally such screening should be tested in a randomised trial. The avoidance and active management of vascular risk factors should also be part of the management of at risk subjects.

Aneurysm, Ruptured↗

PubMed2002

Is diffusion imaging appearance an independent predictor of outcome after ischemic stroke?

BACKGROUND: MR diffusion-weighted imaging (DWI) in ischemic stroke can be quantified by calculating the apparent diffusion coefficient (ADC) or measuring lesion volume. OBJECTIVE: To clarify the association between DWI lesion parameters, clinical stroke severity at baseline, and the relationship with functional outcome. METHODS: Consecutive patients with stroke were categorized for stroke type (Oxford Community Stroke Project Classification [OCSP]) and severity (Canadian Neurologic Scale [CN Scale]) before DWI. The ratio of the trace of the apparent diffusion tensor in the ischemic lesion to the mirror image area in the contralateral hemisphere was calculated ( r). The volume of the visible lesion on DWI was measured. Any visible lesion on T2-weighted imaging (T2WI) was noted. All assessments were blind to all other information. A blinded observer obtained a 6-month Rankin score. Univariate and multivariate analyses were performed to test for independent associations with outcome. RESULTS: In 108 patients, those with lower (i.e., more abnormal) r values had more severe strokes according to the CN Scale (p = 0.01) and the OCSP stroke type (p = 0.002), a large lesion on DWI (p = 0.05), a visible lesion on T2WI (p = 0.001), and poor 6-month functional outcome (p = 0.009). However, on logistic regression, neither r nor DWI lesion volume were independent predictors of 6-month outcome over and above age and stroke severity. CONCLUSION: The r is associated with functional outcome, but that is because it and DWI lesion volume are also associated with stroke severity. Although DWI lesion features are univariate surrogate outcome predictors, the authors were unable to show that they were independent outcome predictors in the current study. Differences between these and other results may be due to differences in study design, sample size, and case mix.

Adult↗

PubMed2002

Intracranial capacity and brain volumes are associated with cognition in healthy elderly men.

BACKGROUND: Brain size and intracranial capacity are correlated with cognitive performance in young healthy adults, but data are lacking on these relationships in older healthy adults. OBJECTIVE: To test the hypotheses that intracranial capacity, volumes of specific brain regions, and a measure of the shared variance between brain regions are positively associated with cognitive function in a sample of healthy, unmedicated elderly men (n = 97; mean age 67.8, SD 1.3). METHODS: Individuals underwent MRI, with measurements of intracranial area and volumetric measurements of hippocampi, temporal lobes, and frontal lobes. Cognitive testing included measures of premorbid intelligence, fluid intelligence, verbal memory, visuospatial memory, verbal fluency, and attention and processing speed. RESULTS: Cognitive tests showed significant positive intercorrelations throughout, and regional brain volumes were also universally, significantly, and positively intercorrelated. Intracranial area and several regional brain volumes correlated with tests of premorbid and fluid intelligence and tests of visuospatial memory. Tests of verbal memory and verbal fluency did not correlate significantly with brain volumes. Structural equation modeling demonstrated that the relationships between specific cognitive tests and regional brain volumes could best be summarized by a significant positive relationship between a general brain size factor and a general cognitive factor, and not by associations between individual tests and particular brain regions. CONCLUSIONS: In healthy elderly men, there are significant relationships between multiple cognitive tests and both intracranial capacity and regional brain volumes. These relationships may be largely due to longstanding associations between general cognitive ability and overall brain size.

Aged↗

PubMed2002

Interobserver variability of magnetic resonance angiography in the diagnosis of carotid stenosis--effect of observer experience.

Magnetic resonance angiography (MRA) for determining the degree of carotid stenosis prior to carotid endarterectomy is attractive because it does not have the high morbidity associated with conventional intra-arterial angiography. We assessed the interobserver variability in the estimation of the degree of stenosis amongst observers of different experience. In a prospective study, consecutive patients with transient ischaemic attacks and symptomatic tight carotid stenosis shown by Doppler ultrasound underwent conventional intra-arterial angiography and 2-D and 3-D time-of-flight MRA of the carotid bifurcations. The films of the processed MRA images were reviewed blind to other clinical and imaging data by eight observers of different levels of experience and coded for the presence and degree of stenosis. The stenosis on intra-arterial angiography was used as the reference standard. There was considerable variability between observers for estimation of the degree of stenosis on MRA. The observers' accuracy ranged from 41% (student) to 79% (experienced). From these estimations, excluding those of the student, it could be seen that up to 23% of patients who would have had an endarterectomy based on MRA should not have done so according to angiography, and up to 33% of patients who should have had an endarterectomy according to angiography would have inappropriately missed having an endarterectomy based on MRA results. Observer reliability of MRA processed images is not good, even in experienced hands. Using the source images and views of the circle of Willis might improve the accuracy, but a further study is required to assess this.

Carotid Artery, Internal↗

PubMed2002

Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders?

OBJECTIVES: Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. METHODS: We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. RESULTS: In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0%, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5%, and the prevalence of severe contralateral stenosis was 4% (OR 1.6, 95% CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. CONCLUSION: Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy.

Carotid Stenosis↗

PubMed2002

Traumatic brain injury and subarachnoid hemorrhage: in vivo occult pathology demonstrated by magnetic resonance spectroscopy may not be "ischaemic". A primary study and review of the literature.

OBJECTIVES: To look for evidence of early ischaemic neurochemical changes in patients suffering severe traumatic brain injury (TBI) and severe subarachnoid haemorrhage (SAH). Proton metabolite concentrations were measured in normal and abnormal areas of brain on T2 MR imaging, in regions considered particularly vulnerable to ischaemic injury. METHODS: Intensive care patients underwent T2 weighted imaging in a 1.5 Tesla MR scanner and proton magnetic resonance spectroscopy (single voxel or chemical shift imaging). Metabolite values in areas that appeared 'normal' and 'abnormal' on T2 MR imaging were compared with those obtained from normal controls. RESULTS: 18 TBI and 6 SAH patients were imaged at 1 to 26 days. N-acetyl aspartate (NAA) was lower in TBI and SAH patients compared to controls in both T2 normal and T2 abnormal areas (p<0.0005). SAH, but not TBI patients also had increased choline and creatine compared to controls in the T2 normal (p<0.02, p<0.02 respectively) and T2 abnormal (p=0.0003, p=0.003) areas. No lactate was found in TBI or SAH patients. CONCLUSIONS: Significant loss of normal functioning neurones was present in TBI and SAH, but no evidence of anaerobic metabolism using lactate as a surrogate marker, questioning the role of 'ischemia' as a major mechanism of damage. Increased choline and creatine were found in SAH patients suggestive of increased cell-wall turnover. Current theories of brain injury after TBI or SAH do not explain these observed neurochemical changes and further research is required.

Adolescent↗

PubMed2002

Who writes guidelines, and who should?

AIM: To confirm or refute the impression that diagnostic radiology was often not represented on guideline writing committees, despite the fact that guidelines often made statements with implications for radiological practice. MATERIALS AND METHODS: We took two approaches. Firstly we examined all published Scottish Intercollegiate Guidelines Network (SIGN) guidelines and extracted the disease topic, the number of authors and peer reviewers, the number that were radiologists, and independently decided whether, given the content, radiologist input at the writing or review stage was necessary. We also searched for all guidelines on management of stroke worldwide (a single disease topic with major radiological implications) and extracted the proportion of authors that were radiologists. RESULTS: Of 47 SIGN guidelines on different diseases, 11 (23%) had a radiologist in the authorship (13/594, 2.2% total authors), and 5/47 (11%) had a radiologist specialist reviewer (10/529, 1.8% total reviewers). Independent review of the guidelines' content suggested that 76% of guidelines should have had a radiologist author and 91% a radiologist reviewer (discrepancy 53% and 80% respectively). Amongst 22 guidelines on acute stroke management in the world literature with 202 authors (where stated), there were only two radiologists (1%), both on one guideline which was specifically to do with imaging of stroke (5% of all stroke guidelines identified). CONCLUSION: Diagnostic radiology is poorly represented on guideline writing committees, although frequently guidelines have implications for radiological practice. Radiologists should try to be more involved in guideline production.

Authorship↗

PubMed2002

Which CT features help predict outcome after head injury?

BACKGROUND: Information collected at baseline can be useful in predicting patient outcome after head injury. The appearance of the CT brain scan may add useful baseline information. The aim of this study was to evaluate which features on the admission CT scan might add significantly to other baseline clinical information for predicting survival in patients with head injury. METHODS: Baseline CT scans were reviewed for patients with all grades of traumatic head injury in a head injury registry, in which baseline demographic and injury status and outcome at 1 year were recorded. Details from the CT scan on haemorrhage, brain swelling, and focal or diffuse damage were noted blind to clinical or outcome information and the scans classified according to the simple seven point grading (normal, mild, moderate, or severe focal injury, mild, moderate, or severe diffuse injury). An existing CT scoring system, the trauma coma databank (TCDB) classification, was also used. Logistic regression modelling was used to test the value of the CT appearance, in addition to the other baseline clinical characteristics, in predicting survival at 1 year. RESULTS: 425 CT scans were read from patients with all severities of injury. Significant independent outcome predictors were age, Glasgow coma score (GCS), pupil reaction, presence of subarachnoid blood, and the simple grading of the overall appearance of the scan (all p<0.001). The TCDB classification was not a significant predictor of outcome. CONCLUSION: Age, GCS, and pupil reaction were all previously shown to be significant predictors of patient survival after head injury. A further two, easy to identify, CT scan variables are independent prognostic variables, and might help to identify patients at high risk of death at the time of admission.

Brain Damage, Chronic↗

PubMed2002

Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy.

OBJECTIVES: To evaluate the accuracy of routinely available non-invasive tests (spiral computed tomographic angiography (CTA), time of flight magnetic resonance angiography (MRA), and colour Doppler ultrasound (DUS)), individually and together, compared with intra-arterial digital subtraction angiography (DSA) in patients with symptomatic tight carotid stenosis; and to assess the effect of substituting non-invasive tests for DSA on outcome, interobserver variability, and patient preference. METHODS: Patients referred from a neurovascular clinic were subjected prospectively to DUS imaging. The operator was blind to symptoms. Patients with a tight carotid stenosis on the symptomatic side were admitted for DSA. CTA and MRA were performed during the admission. The CTA, MRA, and DSA films were each read independently by two of six experienced radiologists, blind to all other data. RESULTS: 67 patients were included (34 had all four imaging procedures). DUS, CTA, and MRA all agreed with DSA in the diagnosis of operable v non-operable disease in about 80% of patients. CTA tended to underestimate (sensitivity 0.65, specificity 1.0), MRA to overestimate (sensitivity 1.0, specificity 0.57), and DUS to agree most closely with (sensitivity 0.85, specificity 0.71) the degree of stenosis as shown by DSA. When using any two of the three non-invasive tests in combination, adding the third if the first two disagreed would result in very few misdiagnoses (about 6%). MRA had similar interobserver variability to CTA (both worse than DSA). Patients preferred CTA over MRA and DSA. CONCLUSIONS: DUS, CTA, and MRA all show similar accuracy in the diagnosis of symptomatic carotid stenosis. No technique on its own is accurate enough to replace DSA. Two non-invasive techniques in combination, and adding a third if the first two disagree, appears more accurate, but may still result in diagnostic errors.

Carotid Stenosis↗

PubMed2002

Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size.

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).

Acromegaly↗

PubMed2001

Imaging appearance of the symptomatic perforating artery in patients with lacunar infarction: occlusion or other vascular pathology?

Lacunar infarction is associated with distinct clinical features. It is thought to result from occlusion of a deep perforating artery in the basal ganglia, centrum semiovale, or brain stem. However, occluded perforating arteries have only rarely been observed at postmortem in patients with lacunar stroke and have not been noted previously on imaging despite the increasing sophistication of the techniques. We observed nine patients with lacunar stroke imaged with computed tomography and magnetic resonance imaging in whom we observed a linear structure with density or signal features consistent with an occluded (or at least abnormal) perforating artery associated with the relevant lacunar infarct. The appearance might also have been caused by a leak of blood and fluid into the perivascular space around the artery, as in several patients the width of the tubular vessel-like structure (>1 mm in diameter) was greater than the expected width of a perforating artery (<0.8 mm in diameter). This interpretation is supported by the fact that the area of infarction was usually around the abnormal vessel, not at the end of it. We describe the patients' clinical and imaging features, and discuss alternative explanations for the imaging appearance and the implications for gaining insights into the cause of lacunar infarction.

Aged↗

PubMed2001

Accuracy and reproducibility of simple cross-sectional linear and area measurements of brain structures and their comparison with volume measurements.

Volumetric measurement of brain structure on brain images is regarded as a gold standard, yet is very time consuming. We wondered whether simple linear and area measurements might be as accurate and reproducible. Two observers independently measured the cross-sectional area of the corpus callosum, lentiform and caudate nuclei, thalamus, amygdalas, hippocampi, lateral and third ventricles, and the width of the sylvian and frontal interhemispheric fissures and brain stem on brain MRI of 55 patients using a program written in-house; one observer also measured the volumes of the basal ganglia, amygdalo-hippocampal complex and ventricular system using Analyze, and performed qualitative assessment of four regions (lateral and third ventricles, cortex, and medial temporal lobe) using the Lieberman score. All measures were performed blinded to all other information. Test objects of known size were also imaged with MRI and measured by the two observers using the in-house program. The true sizes of the test objects were measured using engineering calipers by two observers blind to the MRI results. Differences between the two observers using the same measurement method, and one observer using different methods, were calculated. The simple linear and cross-sectional area measurements were rapid (20 min versus 5 h for volumetric); were highly accurate for test-object measurement versus true size; had excellent intraobserver reliability; and, for most brain structures, the simple measures correlated highly significantly with volumetric measures. The simple measures were in general highly reproducible, the difference (as a percentage of the area or width of a region) between the two raters being around 10%, range 0.1%-14.1%, (similar to inter-rater variability in previous studies of volume measurements). The simple linear and area measures are reproducible and correlate well with the measured volumes, and there is a considerable time saving with the former. In circumstances where a large volume of work precludes detailed volume measurement, simple methods are reliable and can be used instead.

Brain↗