Imaging markers of small vessel disease and brain frailty, and outcomes in acute stroke.

OBJECTIVE: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS randomized 4,011 patients with acute stroke (<48 hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables. RESULTS: In all participants and those with lacunar syndrome (LACS; 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.24; brain frailty score OR 1.25, 95% CI 1.17-1.34; those with LACS: SVD score OR 1.30, 95% CI 1.15-1.47, brain frailty score OR 1.28, 95% CI 1.14-1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS. CONCLUSIONS: Baseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making. IDENTIFIER: ISRCTN99414122.

Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial.

BACKGROUND AND PURPOSE: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. RESULTS: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. CONCLUSIONS: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.

Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis.

BACKGROUND AND PURPOSE: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. CONCLUSIONS: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.

Comparison of 640-Slice Multidetector Computed Tomography Versus 32-Slice MDCT for Imaging of the Osteo-odonto-keratoprosthesis Lamina.

PURPOSE: To investigate the efficacy of 640-slice multidetector computed tomography (MDCT) for detecting osteo-odonto laminar resorption in the osteo-odonto-keratoprosthesis (OOKP) compared with the current standard 32-slice MDCT. METHODS: Explanted OOKP laminae and bone-dentine fragments were scanned using 640-slice MDCT (Aquilion ONE; Toshiba) and 32-slice MDCT (LightSpeed Pro32; GE Healthcare). Pertinent comparisons including image quality, radiation dose, and scanning parameters were made. RESULTS: Benefits of 640-slice MDCT over 32-slice MDCT were shown. Key comparisons of 640-slice MDCT versus 32-slice MDCT included the following: percentage difference and correlation coefficient between radiological and anatomical measurements, 1.35% versus 3.67% and 0.9961 versus 0.9882, respectively; dose-length product, 63.50 versus 70.26; rotation time, 0.175 seconds versus 1.000 seconds; and detector coverage width, 16 cm versus 2 cm. CONCLUSIONS: Resorption of the osteo-odonto lamina after OOKP surgery can result in potentially sight-threatening complications, hence it warrants regular monitoring and timely intervention. MDCT remains the gold standard for radiological assessment of laminar resorption, which facilitates detection of subtle laminar changes earlier than the onset of clinical signs, thus indicating when preemptive measures can be taken. The 640-slice MDCT exhibits several advantages over traditional 32-slice MDCT. However, such benefits may not offset cost implications, except in rare cases, such as in young patients who might undergo years of radiation exposure.

Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

BACKGROUND: Poor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials. METHODS: Clinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures. RESULTS: ICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm(3), respectively (p<0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96-0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95-0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95-0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm(3), p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm(3), p<0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases. CONCLUSIONS: Formal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume. CLINICAL TRIAL REGISTRATION: ISRCTN9941422.

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke.

BACKGROUND: Stroke is a leading cause of death and disability world wide. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is licensed for treatment of acute ischaemic stroke in the early hours after symptom onset. It has been shown in randomised controlled trials (RCTs) and the 2009 Cochrane review of thrombolysis for acute ischaemic stroke to reduce dependency but at the increased risk of intracranial haemorrhage. Methods to reduce the risk of haemorrhage while retaining or enhancing the benefit could increase the use of thrombolytic treatment. While most available information comes from RCTs of intravenous rt-PA at 0.9 mg/kg, it is possible that other doses, drugs and other routes of administration might increase benefit and reduce the hazard. OBJECTIVES: To assess the risks and benefits of different thrombolytic agents, doses and routes of administration for the treatment of acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2012), MEDLINE (1966 to May 2012) and EMBASE (1980 to May 2012). We handsearched journals and conference proceedings, searched ongoing trials registers and contacted pharmaceutical companies and researchers. SELECTION CRITERIA: Unconfounded randomised and quasi-randomised trials of different doses of a thrombolytic agent, or different agents, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality, and extracted the data using a structured proforma. We cross-checked and resolved discrepancies by discussion to reach consensus. We obtained translations and additional information from study authors where required. MAIN RESULTS: We included 20 trials involving 2527 patients. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator, urokinase, desmoteplase or tenecteplase) were compared in 13 trials (N = 1433 patients). Different agents (tissue plasminogen activator versus urokinase, tissue-cultured urokinase versus conventional urokinase, tenecteplase versus tissue plasminogen activator) were compared in five trials (N = 875 patients). Five trials (N = 485) compared different routes of administration. As some trials compared different agents and different doses, some patients contributed to two analyses. There was an approximately three-fold increase in fatal intracranial haemorrhages in patients allocated to higher than to lower doses of the same thrombolytic drug (odds ratio (OR) 2.71, 95% confidence interval (CI) 1.22 to 6.04). There was no difference in the number of patients who were dead or dependent at the end of follow-up between those allocated higher or lower doses of thrombolytic drug (OR 0.86, 95% CI 0.62 to 1.19). Higher versus lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39). There was no evidence of any benefit for intra-arterial over intravenous treatment. AUTHORS' CONCLUSIONS: These limited data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, for acute ischaemic stroke. At present, intravenous rt-PA at 0.9mg/kg as licensed in many countries appears to represent best practice and other drugs, doses or routes of administration should only be used in randomised controlled trials.

The fornix in health and disease: an imaging review.

The fornix is a discrete white matter tract bundle that is critical for normal cognitive functioning. Although clearly visualized at magnetic resonance imaging, its involvement in pathologic processes is often overlooked. Certain disease processes show a predilection for involvement of the fornix; in other pathologic conditions, its involvement is a rare but recognized finding. As part of the Papez circuit, it is critical in formation of memory, with damage or disease resulting in anterograde amnesia. Many different pathologic conditions can affect the fornix. Midline tumors such as gliomas or lymphoma can infiltrate it. As part of the limbic system, it may be affected by herpes simplex encephalitis. Involvement by inflammatory conditions such as multiple sclerosis may illustrate its importance in global cognitive function. An appreciation of forniceal atrophy may aid in assessment of mesial temporal sclerosis. Metabolic conditions such as Wernicke encephalopathy have been reported to involve it. The original discoveries of its role in memory arose from surgical trauma, but as a midline structure, it is susceptible to the shearing forces of diffuse axonal injury. Infarction of the fornix is rare but can result in acute amnesic syndromes. Its role in degenerative conditions such as Alzheimer disease and psychiatric conditions such as schizophrenia is a topic of research interest. Recognition of involvement of the fornix by various pathologic processes may aid in explaining the troubling clinical symptoms of amnesia.

An organ of Zuckerkandl tumour shown by MRA (2007: 12b).

Pheochromocytomas are catecholamine-releasing tumors that can be found in an extraadrenal location in 10% of the cases. Almost half of all pheochromocytomas are now discovered incidentally during cross-sectional imaging for unrelated causes. We present a case of a paragaglioma of the organ of Zuckerkandl that was discovered incidentally during a magnetic resonance angiogram performed for intermittent claudication. Subsequent investigation with computed tompgraphy and I-123 metaiodobenzylguanine scintigraphy as well as an overview of the literature are also presented.

Coil embolization of ruptured middle cerebral artery aneurysms in the first 2 months of life. Report of two cases.

Intracranial artery aneurysms are very rare in infants. There have been no previous reports of coil embolization to branches of the middle cerebral artery (MCA) in infants. The authors describe successful embolization of ruptured aneurysms of the right frontoopercular MCA branch in a 31-day-old infant, and of the left sylvian MCA branch in a 54-day-old infant. One of the cases involves a dissection flap. The authors also review cases in which coil embolization was used for intracranial aneurysms in the first 2 months of life.

Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.

PURPOSE: To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. RESULTS: A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). CONCLUSION: These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique.