Impaired Cerebral Vasoreactivity Research Articles

The clinical and neuroimaging differences between vascular parkinsonism and Parkinson's disease: a case-control study.

Parkinson's disease (PD) and vascular parkinsonism (VaP) have highly overlapping phenotypes, and different prognosis. This study comprehensively investigated the clinical, brain MRI and transcranial sonography differences between VaP and PD. Forty-eight patients with PD, 27 patients with VaP, and 29 healthy controls were compared. All patients were assessed using the MDS-UPDRS, Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), Time Up and Go Test, and Non-Motor Symptoms Scale. Beck Depression Inventory, PD questionnaire- 39, international urine incontinence scale, cognitive assessment scales, MRI brain and transcranial colour-coded doppler. The study was registered on clinical-Trial.gov (NCT04308135) on 03/12/2020. VaP patients showed significantly older age of onset, shorter disease duration, lower drug doses and levodopa responsiveness, higher On and Off axial scores, On and Off BBS, higher On scores for PIGD, rigidity, bradykinesia and total motor MDS-UPDRS, lower On and Off tremor, lower-half predominance, lower asymmetrical presentation and symmetric index than PD patients. VaP patients had worse non-motor symptoms Scale (NMSS) than controls except for perceptual problems/hallucinations but better symptoms than PD patients except for urinary dysfunction. Quality of life (QoL) was impaired in VaP patients and was correlated with motor function and NMSs. The VaP group had significantly higher white matter lesions and brain atrophy, with lower hyperechogenicity of the substantia nigra and more impaired cerebral vascular resistance and vasoreactivity than the PD group. VaP has a characteristic motor and non-motor profile, with impaired QoL, white matter, and transcranial sonography abnormalities that differentiate it from PD. Further studies are warranted to explore the role of vascular lesions in the pathogenesis of VaP. The registered identifier NCT04308135 on clinical-Trial.gov. Registered on 03/12/2020.

Cerebral vasoreactivity, a surrogate marker of cerebrovascular disease, is not impaired in subjects with lifetime, untreated, congenital isolated GH deficiency.

Cerebrovascular disease (CeVD) is a major cause of death and disability. The role of the GH/IGF-I axis on CeVD risk is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit CeVD predisposing factors, like low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness, a surrogate marker of atherosclerosis. However, several confounders such as the primary hypothalamic-pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Therefore, we decided to assess cerebral vasoreactivity, a surrogate marker of CeVD, in adult subjects with untreated isolated GHD (IGHD) due to the same homozygous null mutation in the GHRH receptor gene. A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, intima-media thickness measurement, and transcranial Doppler were performed. The intracranial hemodynamics (mean flow velocity, pulsatility and resistance indexes) were measured, and the response to the vasodilatory stimulus by breath-holding maneuver (breath-holding index) was calculated. IGHD and control groups were similar in Framingham risk score and intima-media thickness. Similarly, there was no difference in mean flow velocity, pulsatility, resistance, and breath-holding index. Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity.

Cerebral Vasoreactivity in Children with Sickle Cell Disease: A Transcranial Doppler Study

BackgroundImpairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with sickle cell disease (SCD) and might play a role in the pathophysiology of stroke in such patients. We examined the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared with healthy age- and gender-matched controls. MethodsPatients were recruited from our hematology outpatient clinic. All SCD patients aged 10-18 years without a history of symptomatic stroke as well as age- and gender-matched healthy children were evaluated with transcranial Doppler (TCD) ultrasonography, with breath-holding maneuver. Breath-holding index (BHI) was calculated by dividing the percentage increase in mean flow velocity occurring during breath holding by the length of time subjects hold their breath after a normal inspiration. BHI was considered abnormal if less than .69. ResultsTCD was performed in 42 patients (mean age 12.7 ± 2.2 years) and 20 controls (mean age 13.90 ± 3.04 years). Blood flow velocities were higher in patients with SCD than in controls in all arteries evaluated (P < .001). BHI values in patients with SCD were significantly lower than in control subjects (1.27 ± .65 versus 1.74 ± .15, P = .013 on the left and 1.16 ± .45 versus 1.61 ± .11, P = .002 on the right). BHI was abnormal in 19% of the patients and in none of the controls, P = .036. ConclusionsChildren with SCD may have impaired cerebral vasoreactivity, with low BHI values suggesting a reduced autoregulation capacity.

The growing clinical spectrum of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is diagnosed primarily as a cause of lobar intracerebral hemorrhages (ICH) in elderly patients. With improving MRI techniques, however, the role of CAA in causing other symptoms has become clear. Recognizing the full clinical spectrum of CAA is important for diagnosis and treatment. In this review we summarize recent insights in clinical CAA features, MRI biomarkers, and management. The rate of ICH recurrence in CAA is among the highest of all stroke subtypes. Cortical superficial siderosis (cSS) and cortical subarachnoid hemorrhage (cSAH) are important imaging predictors for recurrent ICH. CAA also causes cognitive problems in multiple domains. In patients with nondemented CAA, the risk of developing dementia is high especially after ICH. CAA pathology probably starts years before the first clinical manifestations. The first signs in hereditary CAA are white matter lesions, cortical microinfarcts, and impaired occipital cerebral vasoreactivity. Visible centrum semiovale perivascular spaces, lobar located lacunes, and cortical atrophy are new nonhemorrhagic MRI markers. CAA should be in the differential diagnosis of elderly patients with lobar ICH but also in those with cognitive decline and episodic transient neurological symptoms. Physicians should be aware of the cognitive effects of CAA. In patients with a previous ICH, cSS, or cSAH, anticoagulation should be considered risky. The increasing number of MRI markers may help to discriminate CAA from other small vessel diseases and dementia subtypes.

Cerebral vasoreactivity and intima-media thickness in Down syndrome: A case-control study

Subjects with Down Syndrome (DS) have high prevalence of cerebral vascular amyloidosis, cognitive decline and dementia. In Alzheimer Disease, impaired vasoreactivity has been reported as the results of vascular amyloid deposition. Aim of our study was to verify presence of impaired cerebral vasoreactivity and to study carotid intima media-thickness (IMT) by carotid and transcranial ultrasound. We studied 25 DS and compared them with 25 age- and sex-matched normal controls. Vasomotor reactivity was evaluated by means of breath-holding index (BHI) test. There was no difference in IMT, both considering the two side separately (left: 0.70±0.10 vs 0.69±0.12mm, p=0.6) (right: 0.67±0.13 vs 0.68±0.10mm, p=0.5), and considering the sum of both sides (1.38±0.22 vs 1.38±0.23mm, p=1). There was a significant difference in peak systolic velocities (PSV) (139.75±27.67 vs. 123.89±25.73cm/s, p=0.04) and in pulsatility index (PI) (0.95±0.14 vs. 0.86±0.12, p=0.02). BHI was significantly lower in DS than in controls (1.15±0.38 vs 1.88±0.72, p<0.001). In conclusion, subjects with DS have increased PSV and PI, and show a reduction of BHI, expression of impaired vasomotor reserve, possibly due to micro-vascular impairment. Larger study with longitudinal design is needed to verify our data.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Cerebral vasoreactivity: Concordance of breath holding test and acetazolamide injection in current practice: 20 cases of asymptomatic carotid artery stenosis

Cerebral vasoreactivity (CVR) is the ability of the brain's vascular system to keep cerebral blood inflow stable. Impaired CVR is a risk marker of stroke in patients with asymptomatic carotid stenosis. The gold standard to assess CVR with transcranial ultrasound is acetazolamide (ACTZ) injection. The breath holding test (BHT) might be easier to perform. CVR proved to be efficient in laboratory conditions but not in routine practice. To study the validity of BHT versus ACTZ in routine practice in a vascular exploration unit in patients with asymptomatic carotid stenosis. Study of concordance of BHT and ACTZ, to assess CVR in patients consecutively explored on the same day. Eighteen patients with 20 carotid stenosis were included. The temporal window was missing in 20% of cases. Only 11 out of the 20 procedures were analyzed. Concordance was low between BHT and ACTZ to assess CVR (k=0.3714). BHT cannot replace ACTZ injection. It might be a first-step test so that ACTZ injection might be avoided if CVR is normal. Our present results must be confirmed by further study enrolling many more patients.

Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.

Abstract 175: Cerebral Vasoreactivity is Impaired in Children with Sickle Cell Disease

Background: Sickle cell disease (SCD) is the most common cause of stroke in children. Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with SCD and might play a role in the pathophysiology of stroke in such patients. We assessed the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared to healthy age-matched subjects. Patients and Methods: Patients were selected from the pediatric outpatient clinic of the Department of Hematology at our University Hospital. All those patients with SCD disease (diagnosis confirmed by hemoglobin electrophoresis on cellulose acetate) without a history of symptomatic stroke aged 10 to 18 years old were evaluated. Healthy children of similar age and gender were also studied. Transcranial Doppler (TCD) was performed in all patients and controls subjects, with breath-holding maneuver and calculation of the breath-holding index (BHI) to assess cerebral vasoreactivity. The BHI was obtained by dividing the percentage increase in mean flow velocity occurring during breath holding by the length of time (seconds) subjects hold their breath after a normal inspiration. BHI was considered abnormal if &lt; 0.69. Results: TCD was performed in 42 patients (mean age 12.7 +/-2.2 years) and 20 controls (mean age 13.90 +/-3.04 years). Blood flow velocities were higher in patients with SCD than in healthy volunteers in all arteries evaluated (p&lt;0.01). Cerebral blood flow velocities were negatively correlated with hemoglobin levels (p&lt;0.05). BHI values in patients with SCD were significantly lower than in control subjects (1.27 +/-0.65 versus 1.74 +/- 0.15, p=0.01 at left and 1.16 +/- 0.45 versus 1.61 +/- 0.11, p&lt;0.01 at right). BHI was abnormal in 19% of the patients and none of the healthy controls (p=0.04). Conclusions: In conclusion, children with SCD may have impaired cerebral vasoreactivity, with low BHI values suggesting a reduced autoregulation capacity in these patients.

Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes.

Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain's microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type-2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.

Clinical Significance of the Champagne Bottle Neck Sign in the Extracranial Carotid Arteries of Patients with Moyamoya Disease.

The champagne bottle neck sign represents a rapid reduction in the extracranial ICA diameters and is a characteristic feature of Moyamoya disease. However, the clinical significance of the champagne bottle neck sign is unclear. We investigated the relationship between the champagne bottle neck sign and the clinical and hemodynamic stages of Moyamoya disease. We analyzed 14 patients with Moyamoya disease before revascularization (5 men, 9 women; age, 43.2 ± 19.3 years). The ratio of the extracranial ICA and common carotid artery diameters was determined using carotid ultrasonography or cerebral angiography; a ratio of < 0.5 was considered champagne bottle neck sign-positive. The clinical disease stage was determined using the Suzuki angiographic grading system. CBF and cerebral vasoreactivity also were measured. The ICA/common carotid artery ratio (expressed as median [interquartile range]) decreased as the clinical stage advanced (stages I-II, 0.71 [0.60-0.77]; stages III-IV, 0.49 [0.45-0.57]; stages V-VI, 0.38 [0.34-0.47]; P < .001). Lower ICA/common carotid artery ratio tended to occur in symptomatic versus asymptomatic arteries (0.47 [0.40-0.53] versus 0.57 [0.40-0.66], respectively; P = .06). Although the ICA/common carotid artery ratio was not related to cerebral perfusion, it decreased as cerebral vasoreactivity decreased (P < .01). All champagne bottle neck sign-positive arteries were classified as Suzuki stage ≥III, 73% were symptomatic, and 89% exhibited reduced cerebral vasoreactivity. In contrast, all champagne bottle neck sign-negative arteries were Suzuki stage ≤III, 67% were asymptomatic, and all showed preserved cerebral vasoreactivity. The champagne bottle neck sign was related to advanced clinical stage, clinical symptoms, and impaired cerebral vasoreactivity. Thus, detection of the champagne bottle neck sign might be useful in determining the clinical and hemodynamic stages of Moyamoya disease.

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia: A Population-Based Study.

Cerebral vasoreactivity (CVR) is a key factor in maintenance of continuous cerebral perfusion and a marker of (micro)vascular damage. We aimed to determine the longitudinal relation between CVR and the risk of dementia in the general population. We determined CVR in nondemented participants who underwent transcranial Doppler with induced hypercapnia from 1997 to 1999, as part of the ongoing population-based Rotterdam Study. We used a Cox model to determine the risk of dementia in relation to CVR, adjusted for age, sex, cardiovascular risk factors, and carotid intima-media thickness. We furthermore determined decline on a cognitive test battery in relation to CVR, using linear mixed models. Among 1629 participants (mean ± SD age 70.6 ± 6.2 years, 46.2% female) with a mean follow-up of 11.5 years, 209 were diagnosed with dementia, of whom 171 had Alzheimer disease. Higher CVR at baseline was associated with lower risk of dementia (adjusted hazard ratio, 95% confidence interval, per SD increase: 0.87, 0.75-1.00) and Alzheimer disease (adjusted hazard ratio, 0.84; 0.71-0.99). This association was more profound in APOEε4 carriers than in noncarriers (adjusted hazard ratio for all dementia: 0.77, 0.60-0.98 versus 0.89, 0.73-1.07). Performance on cognitive tests at baseline was better with higher CVR (g-factor: P=0.02), but during 3 cognitive assessments over 11 years of follow-up, higher CVR at baseline was associated with less decline in test scores on the Stroop reading and interference tasks in APOEε4 carriers only (P=0.01 and 0.02, respectively). Impaired CVR is associated with an increased risk of dementia in the general population.

Clinical and Physiological Events That Contribute to the Success Rate of Finding "Optimal" Cerebral Perfusion Pressure in Severe Brain Trauma Patients.

Recently, a concept of an individually targeted level of cerebral perfusion pressure that aims to restore impaired cerebral vasoreactivity has been advocated after traumatic brain injury. The relationship between cerebral perfusion pressure and pressure reactivity index normally is supposed to have a U-shape with its minimum interpreted as the value of "optimal" cerebral perfusion pressure. The aim of this study is to investigate the relation between the absence of the optimal cerebral perfusion pressure curve and physiological variables, clinical factors, and interventions. Retrospective analysis of prospectively collected data. Neurocritical care units in two university centers. Between May 2012 and December 2013, a total of 48 traumatic brain injury patients were studied with real-time annotation of predefined clinical events. None. All patients had continuous monitoring of arterial blood pressure, intracranial pressure, and cerebral perfusion pressure, with real-time calculations of pressure reactivity index and optimal cerebral perfusion pressure using ICM+ software (Cambridge Enterprise, University of Cambridge, Cambridge, UK). Selected clinical events were inserted on a daily basis, including changes in physiological variables, sedativeanalgesic drugs, vasoactive drugs, and medical/surgical therapies for intracranial hypertension. The collected data were divided into 4-hour periods, with the primary outcome being absence of the optimal cerebral perfusion pressure curve. For every period, mean values (± SDs) of arterial blood pressure, intracranial pressure, pressure reactivity index, and other physiological variables were calculated; clinical events were organized using predefined scales. In 28% of all 1,561 periods, an optimal cerebral perfusion pressure curve was absent. A generalized linear mixed model with binary logistic regression was fitted. Absence of slow arterial blood pressure waves (odds ratio, 2.7; p < 0.001), higher pressure reactivity index values (odds ratio, 2.9; p < 0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p < 0.01), and following decompressive craniectomy (odds ratio, 1.8; p < 0.01) were independently associated with optimal cerebral perfusion pressure curve absence. This study identified six factors that were independently associated with absence of optimal cerebral perfusion pressure curves.

Diabetic microangiopathy: impact of impaired cerebral vasoreactivity and delayed angiogenesis after permanent middle cerebral artery occlusion on stroke damage and cerebral repair in mice.

Diabetes increases the risk of stroke by three, increases related mortality, and delays recovery. We aimed to characterize functional and structural alterations in cerebral microvasculature before and after experimental cerebral ischemia in a mouse model of type 1 diabetes. We hypothesized that preexisting brain microvascular disease in patients with diabetes might partly explain increased stroke severity and impact on outcome. Diabetes was induced in 4-week-old C57Bl/6J mice by intraperitoneal injections of streptozotocin (60 mg/kg). After 8 weeks of diabetes, the vasoreactivity of the neurovascular network to CO2 was abolished and was not reversed by nitric oxide (NO) donor administration; endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) mRNA, phospho-eNOS protein, nNOS, and phospho-nNOS protein were significantly decreased; angiogenic and vessel maturation factors (vascular endothelial growth factor a [VEGFa], angiopoietin 1 (Ang1), Ang2, transforming growth factor-β [TGF-β], and platelet-derived growth factor-β [PDGF-β]) and blood-brain barrier (BBB) occludin and zona occludens 1 (ZO-1) expression were significantly decreased; and microvessel density was increased without changes in ultrastructural imaging. After permanent focal cerebral ischemia induction, infarct volume and neurological deficit were significantly increased at D1 and D7, and neuronal death (TUNEL+ / NeuN+ cells) and BBB permeability (extravasation of Evans blue) at D1. At D7, CD31+ / Ki67+ double-immunolabeled cells and VEGFa and Ang2 expression were significantly increased, indicating delayed angiogenesis. We show that cerebral microangiopathy thus partly explains stroke severity in diabetes.

Abstract 164: Comparison Between Transcranial Doppler and Functional MRI With Breath Holding Test for Cerebral Vasoreactivity Assessment in Patients with Carotid Stenosis

Background: Impaired cerebral vasoreactivity (CVR) detected by Transcranial Doppler (TCD) is predictive of stroke in patients with carotid stenosis. Functional MRI (fMRI) can evaluate CVR either. Few studies have compared both methods for CVR assessment already. However, none of them used breath holding test (BHT) as the vasodilatory stimulus. Objectives: To assess CVR through BHT using TCD and fMRI in patients with carotid stenosis and controls in order to verify whether fMRI can detect any difference on BOLD-signal intensities between these groups. Additionally, we aimed to verify if fMRI can discriminate correctly any subject with impaired CVR as compared to TCD. Methods: Fifteen patients with carotid stenosis defined as stenosis ≥50% by angiography or ≥70% by ultrasound or ≥70% by CTA or MRA (11men;52-90yo;mean:67.7yo) and 7 matched-controls (5men:51-85yo;mean:64.6yo) performed BHT during TCD. Impaired CVR was diagnosed if mean percentage increase of MCA velocities ≤31% on 3-consecutive intervals of 30s of apnea intercalated by 4-minute-interval of normal breathing. During fMRI, BHT was performed using a traffic lights-based code for instruction on when it was time to stop breathing and was composed by 3-consecutive intervals of 24s of apnea intercalated by 4-minute-intervals of normal breathing. BOLD-signal intensity was measured in the lentiform nucleus ipsilateral to the carotid stenosis. In controls, the mean signal intensity of both lentiform nuclei was considered. Results: Patients and controls showed significantly different BOLD-signal intensities (p:0,0053). Based on CVR defined by TCD, there was an agreement between TCD and fMRI of 6/7 (85,7%) in controls, 11/15 (73.3%) in patients, and 17/22 (77,2%) overall. Conclusion: fMRI showed different BOLD signal intensities in patients and controls using BHT as the vasodilatory stimulus for CVR assessment. Additionally, there was a good agreement between fMRI and TCD on detecting patients with impaired CVR. Further studies are needed to evaluate whether impaired CVR on fMRI with BHT is predictive of stroke in patients with carotid stenosis, but these results suggest that fMRI may be a potentially useful tool for stroke risk assessment in clinical practice.

Heterogeneous Cerebral Vasoreactivity Dynamics in Patients with Carotid Stenosis

Cerebral vasoreactivity (CVR) can be assessed by functional MRI (fMRI) using hypercapnia challenges. In normal subjects, studies have shown temporal variability of CVR blood oxygenation level-dependent responses among different brain regions. In the current study, we analyzed the variability of BOLD CVR dynamics by fMRI with a breath-holding task in 17 subjects with unilateral carotid stenosis before they received carotid stenting. Great heterogeneity of CVR dynamics was observed when comparing BOLD responses between ipsilateral and contralateral hemispheres in each patient, especially in middle cerebral artery (MCA) territories. While some subjects (n=12) had similar CVR responses between either hemisphere, the others (n=5) had a poorly correlated pattern of BOLD changes between ipsilateral and contralateral hemispheres. In the latter group, defined as impaired CVR, post-stenting perfusion tended to be more significantly increased. Our data provides the first observation of divergent temporal BOLD responses during breath holding in patients with carotid stenosis. The development of collateral circulation and the derangement of cerebral hemodynamics can be detected through this novel analysis of the different patterns of BOLD changes. The results also help in prediction of robust increase of perfusion or hyperperfusion after carotid stenting.

Cerebral vasoreactivity with breath holding test in Transcranial Doppler and functional MRI in patients with carotid stenosis

Background: Impaired cerebral vasoreactivity (CVR) on Transcranial Doppler (TCD) with breath holding test (BHT) is predictive of stroke in patients with carotid stenosis. Functional MRI (fMRI) through BOLD-signal change can also /INS;evaluate the hemodynamic response, with the advantage of imaging resolution. Few studies have shown a good correlation between these methods, but none of them used BHT.

Abstract TP139: Usefulness of Staged Angioplasty for Carotid Artery Stenting

Introduction: Hyperperfusion syndrome is one of the most serious complications after carotid revascularization. We report the efficacy of staged angioplasty (SAP) for patients with severely impaired cerebral vasoreactivity. Methods: From April 2008 to March 2012, seventeen of 83 patients with high-grade internal carotid artery stenosis were considered at high risk of postoperative hyperperfusion based on the results of preoperative single-photon emission computed tomography (SPECT) with acetazolamide. They were treated with SAP which consists of mild balloon angioplasty (1st stage) and carotid artery stenting one month later (2nd stage). Rest 123I-IMP SPECT was performed to evaluate hyperperfusion just after the procedure of each stage. Results: Before we induced SAP procedure, 1.9%(3 of 158) of patients treated with CAS had a hemorrhagic complication due to hyperperfusion. None of 17 patients treated with SAP had hyperperfusion phenomenon on SPECT, and a hemorrhagic complication. The mean rate of stenosis was 91% before treatment, 70% after 1st stage, 21% after 2nd stage. Although stenosis had been worsened during the period between 1st and 2nd stages in four patients, all patients showed satisfactory recovery of cerebral blood flow after 2nd stage. Conclusions: In selected patients, SAP is effective and relatively safe to decrease hyperperfusion syndrome after procedures. However, method to choose high-risk patient for postoperative hyperperfusion and protocol of treatment are still controversial.

Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI

To evaluate the cerebral vasoreactivity using blood oxygenation level dependent functional MRI during carbogen inhalation with 7% CO(2) in Alzheimer's disease and amnestic mild cognitive impairment. Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5T during a block-design carbogen inhalation paradigm, with a high concentration face-mask under physiological monitoring. Basal cerebral perfusion was measured using pulsed arterial spin labeling. Image analyses were conducted using Matlab® and SPM5 with physiological regressors and corrected for partial volume effect. Among selected participants, 12 subjects were excluded because of incomplete protocol, leaving for analysis 27 subjects without significant microangiopathy diagnosed for Alzheimer's disease (n=9), amnestic mild cognitive impairment (n=7), and matched controls (n=11). No adverse reaction related to the CO(2) challenge was reported. Carbogen inhalation induced a whole-brain signal increase, predominant in the gray matter. In patients, signal changes corrected for gray matter partial volume were decreased (0.36±0.13% BOLD/mmHg in Alzheimer's disease, 0.36±0.12 in patients with mild cognitive impairment, 0.62±0.20 in controls). Cerebral vasoreactivity impairments were diffuse but seemed predominant in posterior areas. The basal hypoperfusion in Alzheimer's disease was not significantly different from patients with mild cognitive impairment and controls. Among clinical and biological parameters, no effect of apoE4 genotype was detected. Cerebral vasoreactivity values were correlated with cognitive performances and hippocampal volumes. Among age and hippocampal atrophy, mean CVR was the best predictor of the mini-mental status examination. This BOLD functional MRI study on CO(2) challenge shows impaired cerebral vasoreactivity in patients with Alzheimer's disease and amnestic mild cognitive impairment at the individual level. These preliminary findings using a new MRI approach may help to better characterize patients with cognitive disorders in clinical practice and further investigate vaso-protective therapeutics.

Impaired cerebral vasoreactivity may cause cerebral blood volume dip following obstructive sleep apnea termination

Impaired cerebral vasoreactivity may cause cerebral blood volume dip following obstructive sleep apnea termination