Effects of aging on the association between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness.

Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older = 106 ± 17%, p < 0.001) and systemic (young = 59 ± 9% and older = 80 ± 9%, p < 0.001) augmentation indices (AI) were higher in the older group. CBF responses to VS (PCA: p < 0.026) and hypercapnia (PCA: p = 0.018; MCA: p = 0.042) were lower in the older group. A curvilinear model fitted to cerebral AI and age showed AI increases until ~60 years of age, after which the increase levels off (PCA: R (2) = 0.45, p < 0.001; MCA: R (2) = 0.31, p < 0.001). Finally, MCA, but not PCA, hypercapnic reactivity was inversely related to cerebral AI (MCA: R (2) = 0.28, p = 0.002; PCA: R (2) = 0.10, p = 0.104). A similar inverse relationship was not observed with the PCA blood flow response to VS (R (2) = 0.06, p = 0.174). In conclusion, older subjects had reduced neurovascular- and hypercapnia-mediated CBF responses. Furthermore, lower hypercapnia-mediated blood flow responses through the MCA were associated with increased vascular stiffness. These findings suggest the reduced hypercapnia-evoked CBF responses through the MCA, in older individuals may be secondary to vascular stiffening.

Measurement of length of hyperdense MCA sign in acute ischemic stroke predicts disappearance after IV tPA.

BACKGROUND: We sought to assess the hypothesis that length and volumes of middle cerebral artery (MCA) thrombus were associated with disappearance of the hyperdense middle cerebral artery sign (HMCAS) in acute ischemic stroke. METHODS: This is a retrospective cohort study of acute ischemic stroke patients with MCA occlusion admitted to the University Hospital in Canada. The length and volumes of the HMCAS was measured on the plain CT by placing CTA images (CTA source images or MIP images) side-by-side. RESULTS: Seventy-six patients with acute stroke having HMCAS on noncontrast CT (NCCT) with M1 MCA occlusion confirmed by CT angiography or digital subtraction angiography and received tPA. The treatments received were: IV tPA 41(53.9%) and endovascular treatment ± IV tPA 35 (46.1%). In the IV tPA group, the rate of disappearance varied depending on the baseline HMCAS length. Short length HMCAS (<10 mm) disappeared in 6/7 (85.7%) (P < .001). Medium length HMCAS (10-20 mm) disappeared in 9/24 (37.5%). No cases of long length HMCAS (>20 mm) disappeared (0/10) (P = .05). Rate of disappearance of HMCAS was found to be volume dependent (P < .002). CONCLUSION: HMCAS length >10 mm infrequently disappears with IV tPA suggesting a potential need for ancillary therapy in this group.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. METHODS: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Outcomes in acute ischemic strokes presenting with disabling neurologic deficits without intracranial vascular occlusion.

BACKGROUND: Patients with moderate to severe acute ischemic stroke without intracranial vessel occlusion are an intriguing subset of stroke patients. They pose diagnostic and therapeutic challenges to the physician. We sought to study these patients with an emphasis on their radiological and clinical outcomes. METHODS: This is a retrospective cohort study of ischemic stroke patients (NIHSS≥6), with no intracranial vessel occlusion on computed tomography angiography within six-hours of symptom onset. Follow-up imaging - either computed tomography brain or magnetic resonance imaging - was performed within one- to seven-days. The primary outcome was modified Rankin Scale score≤2 at three-months. RESULTS: In a database of 1308 patients, we identified 99 (7·6%) patients with NIHSS≥6 and no intracranial vessel occlusion on computed tomography angiography. The mean age was 67·8 ± 15·4 years and 60 (60·6%) were men. The median baseline NIHSS was nine (6-28). The initial computed tomography head was normal in 79 (79·8%) patients. Dramatic early clinical improvement at 24 h (NIHSS score ≤2 at 24 h or change between baseline and 24 h NIHSS score ≥15 points) was seen in 38 (38·4%) patients. Follow-up scans showed infarcts in 66 (66·7%) patients. Fifty (50·5%) patients received tissue plasminogen activator; one (2%) tissue plasminogen activator-treated patient developed symptomatic intracranial hemorrhage. At three-months; 59 (59·6%) patients were independent (modified Rankin Scale≤2), 34 (34·3%) patients were dependent (modified Rankin Scale 3-5), and six (6·1%) were dead. The factors associated with the unlikelihood of good outcome were higher initial NIHSS (odds ratio 0·86 per additional point, 95% confidence interval 0·77-0·95, P=0·003), and older age (odds ratio 0·95 per additional year, 95% confidence interval 0·92-0·98, P=0·004). CONCLUSION: Stroke without intracranial occlusions are not a benign entity. Factors that are independently associated with decreased likelihood of a good outcome are higher baseline NIHSS, and older age. Treatment with tissue plasminogen activator is not a predictor of outcome.