Elevated Transcranial Doppler Velocities Research Articles

Protein biomarkers in patients with subarachnoid hemorrhage, vasospasm, and delayed ischemic neurological deficits.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease. It has many sequelae, including vasospasm and delayed ischemic neurological deficits (DINDs). We explored the blood proteome in patients with aSAH using transcranial Doppler (TCD) velocity as a guide to patients who are at risk for symptomatic vasospasm and DIND. Blood was drawn on all days that patients were observed in the neurocritical care unit (NCCU) after aSAH. A team of neurologists and neurosurgeons identified patients with clinical evidence of vasospasm and DIND. Serum was fractionated using protein chips and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS). We detected a pattern of protein expression associated with those at risk for elevated TCD velocities by day 8, compared with blood collected in the presymptomatic stage (days 1-3). We further analyzed serum using pooled samples from study entry to the time of elevated TCD velocities using a protein microarray that analyzed 500 human proteins thematically oriented toward inflammation. After identifying several candidates with elevated concentrations in the pooled samples, we then used reverse protein arrays to quantitate the concentration of potential candidate proteins in the individual samples. Proteins with significantly elevated concentrations included apolipoprotein-E, apolipoprotein-A, serum amyloid protein-4, and serum amyloid protein-P. Future studies in larger sample populations are needed to evaluate these biomarkers further as representative of biosystems involved in vasospasm and DIND or as potential biomarkers predictive of risk associated with disease.

Is sickle cell disease the same everywhere?

Is sickle cell disease the same everywhere?

Cerebral blood flow velocity and language functioning in pediatric sickle cell disease

We investigated the association of increased cerebral blood flow velocity with specific language abilities in children with sickle cell disease (SCD). Thirty-nine children ages 5 to 8 years old with high-risk genotypes of SCD underwent cognitive testing, which included tests of language skills, visual motor skills, and attention/working memory as part of a routine hematology health-maintenance visit. Transcranial Doppler (TCD) velocities were obtained from review of medical records, with the velocities that were in closest temporal proximity to the cognitive assessment used in the analysis. TCD velocities predicted scores on tests of syntactical skills, even when controlling for anemia severity. Semantic and phonological ability and other cognitive skills were not strongly related to TCD velocities. Elevated blood flow velocities in children with high-risk SCD may contribute to a specific language impairment or to a broader dysfunction of short-term and/or working memory. This study underscores the need for clinicians to monitor language skills of children with SCD who have elevated TCD velocities, as these cognitive abilities might be particularly sensitive to cerebrovascular disruption related to their disease.

Candidate Gene Polymorphisms and Their Association with TCD Velocities in Children with Sickle Cell Disease.

Ischemic stroke occurs in 11% of patients with sickle cell disease (SCD) by age 20. The STOP and STOP-II trials showed that the risk of ischemic stroke increases with Transcranial Doppler (TCD) velocities in major intracranial arteries in children with SCD 2–16 years of age, and that the risk in children with abnormal velocities (>200 cm/sec) can be significantly reduced by prophylactic transfusions. Risk factors for development of high TCD phenotype are not clearly established. In an ancillary study to STOP/STOP-II, we analyzed 28 polymorphisms in 20 candidate genes for association with elevated TCD velocity. DNA was extracted from 130 patients randomized in the STOP trial, all of whom had abnormal TCD velocities, and from 355 patients who were screened for STOP II at 8 participating centers. None of the subjects from either trial had histories of overt stroke when they were screened. Samples from STOP subjects were anonymized according to an IRB-approved plan; informed consent/assent was obtained from subjects screened for the STOP-II trial. Hb phenotype was ascertained by HPLC. High throughput genotyping was performed using the MassARRAY™ System (Sequenom Inc., San Diego, CA) at Mass U. TCD status was classified as normal (<170 cm/sec) or not normal (>170 cm/sec) using the average of all TCDs on each patient, excluding any TCDs obtained after starting transfusion (median: 2 TCD exams, range 1–16). Genotyping results for each SNP were also reduced to a binary classification (mutation present or absent) by combining heterozygous subjects with those homozygous for the mutation. Conditional logistic regression was employed to model the probability of having at least 1copy of the mutant allele as a function of TCD status stratified on age class. Under this approach, the odds ratio (OR) relating TCD status to genotype is assumed to be the same at all ages but the prevalence of abnormal or conditional TCD is allowed to vary with age. Seven SNPs were excluded from analyses: all subjects studied (479) were homozygous for the common allele for 5 SNPs, and only 2 subjects were heterozygous for the minor allele for 2 SNPs. The prevalence of abnormal TCD varied with age; the highest prevalence was found in 8–9 year old subjects. Only one SNP, VCAM G1238C, had a significant OR of 0.6 (p=0.03) suggesting this SNP is protective from high TCD. The same polymorphism was found to be protective from stroke with an OR of 0.3 in a different cohort of patients by Taylor et al (Blood , 100:4303–9, 2002). Several published studies have reported on association of stroke with candidate gene polymorphisms with differing results. This is the first large scale study of the association of abnormal TCD (stroke risk) with genetic polymorphisms. To our knowledge, it is also the first confirmatory genetic association study in SCD and cerebrovascular disease in a different population of subjects. Functional analyses of this polymorphism and association of stroke and candidate gene polymorphisms in this cohort are planned.

Vasospasm and cerebral infarction following isolated intraventricular hemorrhage

Cerebral arterial vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is an important cause of delayed neurologic deterioration. Vasospasm following isolated intraventricular hemorrhage (IVH) is less common. Accepted predictors of vasospasm following SAH include poor Hunt-Hess grade, elevated transcranial Doppler velocities, and the thickness of cisternal blood on neuroimaging [1, 2]. The role of intraventricular hemorrhage in vasospasm is more controversial. Case report and review of the literature. A 41-year-old woman developed symptomatic delayed vasospasm 10 days following isolated IVH due to the rupture of an arteriovenous malformation (AVM). Intraventricular hemorrhage can independently cause significant delayed vasospasm. Possible mechanisms are described.

Cerebral Vasospasm Following Subarachnoid Hemorrhage.

Cerebral vasospasm and related ischemic stroke continue to be significant complicating factors in the course of many patients with subarachnoid hemorrhage from berry aneurysm rupture. The risk of this well-recognized but poorly understood complication can be estimated on the basis of patient medical history, neurologic examination, and head CT findings. Every patient with possible risk needs specialized neurologic intensive care unit care after aneurysm obliteration. Surgical and pharmacologic wash-out of subarachnoid blood around the basal arteries, proper management of intracranial pressure and fluid status, hyponatremia, hypomagnesemia, and fever, as well as use of calcium channel blockers, have been considered helpful in patient management prior to and with the symptomatic vasospasm development. Transcranial Doppler (TCD) ultrasound is important in detecting vasospasm before the patient suffers ischemic neurologic deficit or infarct. Elevated TCD velocities often initiate the use of triple-H (HHH: hypertension, hemodilution, and hypervolemia) therapy and subsequently guide it. Up to the end of the first 3 weeks after subarachnoid hemorrhage and aneurysm obliteration, development of any focal neurologic deficit or mental deterioration, unless convincingly proven otherwise, is assumed to be from cerebral vasospasm. When a hemodynamically significant vasospasm in the arterial segments of clinical concern is suggested, emergency cerebral angiography with balloon dilatation angioplasty or intra-arterial infusion of vasodilating agents may be helpful in relieving ischemic symptoms.

Elevated Transcranial Doppler Ultrasound Velocities Following Therapeutic Arterial Dilation

Elevated transcranial Doppler (TCD) velocities seen after cerebral angioplasty are commonly interpreted as evidence of residual or recurrent stenosis but may conceivably arise from hyperemia and require different clinical management. Four cases of abnormally elevated mean TCD velocities obtained after therapeutic arterial dilation with either balloon angioplasty or intra-arterial administration of papaverine are described. In each case, cerebral angiography revealed a dilated vessel, suggesting that hyperemia and impaired autoregulation were the causes of the high velocities. These examples suggest that high TCD velocities after vessel dilation may be produced by unpredictable amounts of vessel narrowing and flow alteration. Although a normalizing TCD velocity after angioplasty suggests effective vessel dilation, high velocities may be due partly to hyperemia and cannot be interpreted as arising solely from recurrent stenosis.