Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study.

BACKGROUND: Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. METHODS: We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues. RESULTS: While age correlated negatively with normalised penumbral volume (Kendall's τ b=-0.234, p=0.048) and lesion volume (Kendall's τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendall's τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort. CONCLUSIONS: These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.

The value of ambulatory blood pressure in older adults: the Dublin outcome study.

BACKGROUND: ambulatory blood pressure (ABPM) appears to be a more accurate predictor of cardiovascular outcome than blood pressure (BP) measured in the clinic setting in younger adults. OBJECTIVES: the purpose of this study was to determine if ABPM predicted total and cardiovascular mortality independently of clinic BP and other cardiovascular risk factors in those aged 65 years and over. METHODS: one thousand one hundred and forty-four individuals aged 65 and over referred to a single BP clinic had 24-h ABP measurement and clinic measurement at baseline off treatment. There were 385 deaths (of which 246 were cardiovascular) during a mean follow-up period of 6.7 years. RESULTS: with adjustment for gender, age, risk indices and also for clinic BP, a higher mean value of ABPM was an independent predictor of cardiovascular mortality. The relative hazard ratio for each 10-mmHg rise in systolic blood pressure (SBP) was 1.10 (1.06-1.18, P < 0.001) for daytime and 1.18 (1.11-1.25, P < 0.001) for night-time SBP. The hazard ratios for each 5-mmHg rise in diastolic blood pressure (DBP) were 1.05 (1.00-1.10, P = NS) for daytime and 1.09 (1.04-1.14, P < 0.001) for night-time diastolic pressure. The hazard ratios for night-time ABPM remained significant after adjustment for daytime ABPM. CONCLUSIONS: ambulatory measurement of BP is superior to clinic measurement in predicting cardiovascular mortality in elderly subjects. Night-time BP is the strongest predictor of outcome in this age group.

Thrombolysis delivery by a regional telestroke network--experience from the U.K. National Health Service.

BACKGROUND: The majority of established telestroke services are based on "hub-and-spoke" models for providing acute clinical assessment and thrombolysis. We report results from the first year of the successful implementation of a locally based telemedicine network, without the need of 1 or more hub hospitals, across a largely rural landscape. METHODS AND RESULTS: Following a successful pilot phase that demonstrated safety and feasibility, the East of England telestroke project was rolled out across 7 regional hospitals, covering an area of 7500 square miles and a population of 5.6 million to enable out-of-hours access to thrombolysis. Between November 2010 and November 2011, 142 telemedicine consultations were recorded out-of-hours. Seventy-four (52.11%) cases received thrombolysis. Median (IQR) onset-to-needle and door-to-needle times were 169 (141.5 to 201.5) minutes and 94 (72 to 113.5) minutes, respectively. Symptomatic hemorrhage rate was 7.3% and stroke mimic rate was 10.6%. CONCLUSIONS: We demonstrate the safety and effectiveness of a horizontal networking approach for stroke telemedicine, which may be applicable to areas where traditional "hub-and-spoke" models may not be geographically feasible.

Ring chromosome 12 with inverted microduplication of 12p13.3 involving the Von Willebrand Factor gene associated with cryptogenic stroke in a young adult male.

We report a 35-year-old male with a ring chromosome 12 originally diagnosed 20 years prior to presentation with an ischemic stroke. Array CGH analysis revealed a sub-microscopic microdeletion and microduplication within 12p13.3 and a microdeletion in 12q24.33. FISH analysis further revealed that the duplication was in an inverted orientation and included exons 35-52 of the dosage-sensitive Von Willebrand Factor (VWF) gene. Partial duplication of this gene, which has a role in the clotting cascade, suggests a potential mechanism for generating a pro-thrombotic state that may have contributed to a premature cerebrovascular event. Evidence of raised VWF antigen levels and VWF activity levels in the highest quartile provides support for this hypothesis. This case illustrates that when a ring chromosome is identified, the possibility of cryptic genomic rearrangements needs to be considered as these may have implications in predicting natural history.