Cerebrovascular assessments to help understand brain-related changes associated with aerobic exercise after stroke

Evidence suggests exercise is ‘good medicine’ post-stroke, yet consensus is lacking on the time to initiate, type, exertion level, and duration per session. It remains a challenge to identify outcome measures for stroke-exercise trials that are sufficiently sensitive to intervention parameters. Cerebrovascular assessments, namely cerebral blood flow and intracranial pulsatility, are herein discussed as examples of quantitative brain-specific measures that may be useful to monitor exercise-related brain changes and help to guide stroke rehabilitation interventions. Bullets: Cerebral blood flow and arterial stiffness are potential vascular targets for stroke exercise trials.

Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow

Cerebral small vessel disease (SVD) contributes to 25% of ischemic strokes and 45% of dementias. We aimed to investigate the role of cerebral blood flow (CBF) and intracranial pulsatility in SVD. We scanned 60 patients with minor ischemic stroke, representing a range of white matter hyperintensities (WMH). We rated WMH and perivascular spaces (PVS) using semi-quantitative scales and measured WMH volume. We measured flow and pulsatility in the main cerebral vessels and cerebrospinal fluid (CSF) using phase-contrast MRI. We investigated the association between flow, pulsatility and SVD features. In 56/60 patients (40 male, 67.8±8.3 years) with complete data, median WMH volume was 10.7 mL (range 1.4–75.0 mL), representing median 0.77% (0.11–5.17%) of intracranial volume. Greater pulsatility index (PI) in venous sinuses was associated with larger WMH volume (e.g. superior sagittal sinus, β = 1.29, P < 0.01) and more basal ganglia PVS (e.g. odds ratio = 1.38, 95% confidence interval 1.06, 1.79, per 0.1 increase in superior sagittal sinus PI) independently of age, sex and blood pressure. CSF pulsatility and CBF were not associated with SVD features. Our results support a close association of SVD features with increased intracranial pulsatility rather than with low global CBF, and provide potential targets for mechanistic research, treatment and prevention of SVD.

Intracranial pulsatility in patients with cerebral small vessel disease: a systematic review

Growing evidence suggests that increased intracranial pulsatility is associated with cerebral small vessel disease (SVD). We systematically reviewed papers that assessed intracranial pulsatility in subjects with SVD. We included 27 cross-sectional studies (n=3356): 20 used Doppler ultrasound and 7 used phase-contrast MRI. Most studies measured pulsatility in the internal carotid or middle cerebral arteries (ICA, MCA), whereas few assessed veins or cerebrospinal fluid (CSF). Methods to reduce bias and risk factor adjustment were poorly reported. Substantial variation between studies in assessment of SVD and of pulsatility indices precluded a formal meta-analysis. Eight studies compared pulsatility by SVD severity (n=26–159, median = 74.5): arterial pulsatility index was generally higher in more severe SVD (e.g. MCA: standardized mean difference = 3.24, 95% confidence interval [2.40, 4.07]), although most did not match for age. Seventeen studies (n=9–700; median = 110) performed regression or correlation analysis, of which most showed that increased pulsatility was associated with SVD after adjustment for age. In conclusion, most studies support a cross-sectional association between higher pulsatility in large intracranial arteries and SVD. Future studies should minimize bias, adjust for potential confounders, include pulsatility in veins and CSF, and examine longitudinal relationship between pulsatility and SVD. Agreement on reliable measures of intracranial pulsatility would be helpful.

Idiopathic normal pressure hydrocephalus: diagnostic and predictive value of clinical testing, lumbar drainage, and CSF dynamics

OBJECTIVE The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24–72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. RESULTS Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini–Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CONCLUSIONS Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH.

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients

Object Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICPLV) may differ from that within the brain parenchyma (ICPPAR), and whether pulsatility may differ between noncommunicating ventricles. Methods The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICPLV and ICPPAR signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICPLV and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICPLV and ICPPAR signals (6 cases) or ICPLV and ICP4V signals (1 case) were determined. Results There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICPLV) than within brain parenchyma (ICPPAR) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICPLV) ventricles in 1 patient. Differences ≥1 mm Hg in ICP wave amplitude were found in 0.5–100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). Conclusions The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICPLV) than within the brain parenchyma (ICPPAR). This may be one mechanism behind ventricular enlargement in hydrocephalus.