Impaired Vasomotor Reactivity Research Articles

Relationship of Plasma Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) Levels with Cerebrovascular Vasomotor Reactivity in Chronic Migraine Sufferers

Introduction: Migraine is a complex health problem and causes disability, especially in women. The current pathophysiology of migraine is a combination of vascular, neurogenic, and neuroinflammatory theories. PACAP-38 is a vasoactive neuropeptide that increases during migraine attacks. Endothelial dysfunction results in impaired vasomotor reactivity. Analysis of vasomotor reactivity is determined by measuring the breath-holding index (BHI) and migraine vascular index (MVI), where there is a decrease in vasomotor reactivity values ??in migraine sufferers. This study aims to determine PACAP-38 levels in chronic migraine sufferers and their relationship to cerebrovascular vasomotor reactivity.
 Methods: This research is a comparative study (cross-sectional) that is carried out in hospitals and health centers spread across the city of Padang from May 2022 to June 2023. The research sample consisted of 30 chronic migraine sufferers and 30 healthy controls. Vasomotor reactivity was assessed by determining BHI and MVI values ??using transcranial Doppler. Plasma PACAP-38 levels were measured using the ELISA method. Data analysis was carried out using SPSS.
 Results: The mean value of vasomotor reactivity in chronic migraine sufferers is 0.355. There is a negative correlation between the frequency and duration of migraine attacks and vasomotor reactivity (frequency p=0.032; duration p=0.022). The mean value of PACAP-38 levels in chronic migraine sufferers was 6.15 pg/ml, and in healthy controls, 4.85 pg/ml; there was a significant difference between plasma PACAP-38 levels in chronic migraine sufferers compared to healthy controls. However, there was no significant difference between plasma PACAP-38 levels and vasomotor reactivity in chronic migraine sufferers.
 Conclusion: There is an increase in plasma PACAP-38 levels in chronic migraine sufferers, but there is no significant relationship between plasma PACAP-38 levels and vasomotor reactivity values.

Cerebral Vasomotor Reactivity in COVID-19: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient's disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors.

Simple CaroTID-VasC score to predict one-year risk of stroke in symptomatic carotid stenosis patients

BackgroundA subset of extracranial symptomatic carotid stenosis (ESCS) patients may fare well on current optimal medical therapy (OMT), and surgery may be avoided in these patients. Therefore, we aimed to develop and validate a stroke risk prediction model to stratify the risk among ESCS patients. MethodsAdult ESCS patients who denied revascularization procedures were enrolled prospectively and prescribed OMT. Patients were followed-up for twelve months after assessing the clinical, imaging, and hemodynamics-based risk predictors at baseline. Cox regression analysis was performed on predictors which were significant in univariate analysis. Beta coefficients of significant predictors in Cox regression were used to generate a numeric score. The model was internally validated using bootstrapping. ResultsA total of 20 (20.2%) out of 99 patients had event recurrence during the follow-up. Transient ischemic attack index event (P = 0.014), diabetes mellitus (P = 0.018), contralateral significant stenosis (P = 0.007), echolucent plaque (P = 0.011), and impaired vasomotor reactivity (P = 0.006) were significant predictors in Cox regression analysis. A points score (0–6) was derived from regression coefficients of the significant predictors. The area under ROC was 0.884 for the developed model and 0.832 for the bootstrapped model. Youden's index divided the score into low-risk (2.2%) and high-risk (35.8%) groups, and the difference in risk was significant (P < 0.001). ConclusionsMost ESCS patients benefited from OMT, and the CaroTID-VasC score was effective in stratifying patients for risk of endpoint occurrence. The developed model may help identify high-risk subgroups of ESCS patients and assist the decision-making of carotid interventions.

Acute Revascularization Induced Reversed Robin Hood Syndrome

Paradoxical intracranial hemodynamic steal (IHS) is a contradictory reduction of cerebral blood flow volume in the territory of the impaired perfusion area occurring spontaneously or in response to vasodilatory stimuli, which can be recorded and evaluated on transcranial doppler (TCD). IHS followed by early neurological worsening (change in National Institute of Health Stroke Scale [NIHSS]&gt; 2) in acute ischemic stroke patients has been described as reversed Robin Hood syndrome (RRHS). We describe two cases of RRHS following carotid artery stenting (CAS) in patients with contralateral carotid occlusion and its further management. Two patients with a history of anterior circulation strokes presented with recent complaints of dizziness and a sensation of being pulled back (patient 1), and episodic numbness of upper limbs (patient 2). On CT angiogram, both of the patients had severe extracranial internal carotid artery (ICA) stenosis on the symptomatic side associated with complete occlusion of the ICA on the contralateral side. In addition, both patients had impaired vasomotor reactivity (VMR) on TCD in the bilateral middle cerebral artery (MCA). Therefore, CAS on the symptomatic side was performed in both patients by femoral artery access without any periprocedural and postprocedural complications. However, on day 1 post CAS, complaints of transient upper limb tingling (patient 1) and limb shaking (patient 2) were reported corresponding to the completely occluded ICA, and TCD examinations confirmed RRHS in both patients. Patients were managed by decreasing the dose of antihypertensive medication to augment the blood pressure for 2 weeks. Normalization of the VMR on TCD was seen on follow-up, and both patients remain asymptomatic.

December 2021 Stroke Highlights

December 2021 <i>Stroke</i> Highlights

Assessment of cerebral vasomotor reactivity in patients with acute stroke and transient ischemic attack (TIA) with different etiopathogenesis: Preliminary results

An impaired vasomotor reactivity (VMR) represents a negative prognostic factor for vascular and degenerative cognitive deterioration. Only few studies have addressed VMR in acute phase of stroke. We aim to investigate if VMR, calculated through the breath holding index (BHI), is a prognostic marker of clinical outcome in stroke/TIA patients.

Cerebral vasomotor reactivity in border zone infarcts; a transcranial Doppler study

BackgroundMany reports have emphasized that watershed infarcts are the consequence of hemodynamic compromise, but other reports have suggested that this is not always the case and have suggested that embolization plays a major role in the development of watershed infarcts. Impaired cerebral vasomotor reactivity has certain correlates in watershed hypoperfusion strokes.ObjectivesThis study aimed to assess the role of vasomotor reactivity impairment in watershed infarcts by transcranial Doppler. It also recorded correlates associated with impaired vasomotor reactivity in such patients.MethodologySixty patients with watershed infarction after more than 1 month from onset were studied and grouped into three groups (14 patients with mixed internal and external watershed, 28 patients with internal watershed and 18 patients with external watershed infarcts). Magnetic resonant imaging and angiography of brain, carotid duplex, and echocardiography were done. CO2 reactivity to assess vasomotor reactivity was determined using Doppler.ResultsCerebral vasomotor reactivity was impaired significantly among the internal watershed group compared with the external watershed group (P value = 0.040). In external watershed infarcts, the anterior external watershed group showed significant impairment of vasomotor reactivity compared to posterior external watershed group (P value = 0.046). Impaired cerebral vasomotor reactivity was more evident in diabetic patients and not statistically related with other risk factors. It was also associated with middle cerebral artery stenosis.ConclusionThe hemodynamic impairment is related to internal watershed more than external watershed infarcts, also it is more associated with anterior than posterior external watershed infarcts. Diabetes mellitus is the most correlated cerebrovascular risk factor associated with impaired vasomotor reactivity in such patients.

Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis.

The deep and periventricular white matter is preferentially affected in several neurological disorders, including cerebral small vessel disease (SVD) and multiple sclerosis (MS), suggesting that common pathogenic mechanisms may be involved in this injury. Here we consider the potential pathogenic role of tissue hypoxia in lesion development, arising partly from the vascular anatomy of the affected white matter. Specifically, these regions are supplied by a sparse vasculature fed by long, narrow end arteries/arterioles that are vulnerable to oxygen desaturation if perfusion is reduced (as in SVD, MS and diabetes) or if the surrounding tissue is hypoxic (as in MS, at least). The oxygen crisis is exacerbated by a local preponderance of veins, as these can become highly desaturated 'sinks' for oxygen that deplete it from surrounding tissues. Additional haemodynamic deficiencies, including sluggish flow and impaired vasomotor reactivity and vessel compliance, further exacerbate oxygen insufficiency. The cells most vulnerable to hypoxic damage, including oligodendrocytes, die first, resulting in demyelination. Indeed, in preclinical models, demyelination is prevented if adequate oxygenation is maintained by raising inspired oxygen concentrations. In agreement with this interpretation, there is a predilection of lesions for the anterior and occipital horns of the lateral ventricles, namely regions located at arterial watersheds, or border zones, known to be especially susceptible to hypoperfusion and hypoxia. Finally, mitochondrial dysfunction due to genetic causes, as occurs in leucodystrophies or due to free radical damage, as occurs in MS, will compound any energy insufficiency resulting from hypoxia. Viewing lesion formation from the standpoint of tissue oxygenation not only reveals that lesion distribution is partly predictable, but may also inform new therapeutic strategies.

CEREBRAL VASOMOTOR REACTIVITY IN PATIENTS WITH ARTERIAL HYPERTENSION AND COGNITIVE IMPAIRMENT

Objectives. The aim of our study is to determine whether cerebral vasomotor reactivity is impaired in patients with arterial hypertension and cognitive impairment and how this hemodynamic parameter is associated with different functions of cognition. Materials and methods. We included 87 patients with arterial hypertension divided into two groups, one with neurocognitive impairment ranging from mild to severe aged between 47 and 90 years (70.2 ± 11.4) and the second group without cognitive impairment aged between 41 and 86 years (60.1 ± 11.4). We excluded patients with significant hemodynamic cervico-cerebral arterial stenoses, arrhythmias and other diseases that may impair cerebral vasomotor reactivity. All the patients underwent assessment of vasomotor reactivity and neurocognitive functions. Results. BHI values were significantly lower in the first group of patients compared to the second one. The percent of patients with impaired cerebral vasomotor reactivity was significantly higher in the group of patients with cognitive impairment, as compared to the other group (54.35% vs 29.27%, p=0.01). There was a significant statistical difference between the MMSE, MOCA and clock test scores among patients with and without impaired vasomotor reactivity. This difference was also maintained for visuospatial/executive, naming and language domains of the MOCA test. Conclusions. Impaired cerebral vasomotor reactivity is more frequent in patients with arterial hypertension and cognitive impairment. Patients with arterial hypertension and impaired vasomotor reactivity have poorer cognitive performance, cognitive functions most affected in patients with impaired vasomotor reactivity being language, visuospatial and executive ones.

Reduced breath holding index in patients with chronic migraine

Migraine is a neurovascular disorder characterized by autonomic nervous system dysfunction and severe headache attacks. Studies have shown that changes in the intracranial vessels during migraine have an important role in the pathophysiology. Many studies have been conducted on the increased risk of stroke in patients with migraine, but insufficient data are available on the mechanism underlying the increase. This study aimed to evaluate basal cerebral blood flow velocity and vasomotor reactivity in patients with chronic migraine. We evaluated 38 patients with chronic migraine. Three of them were excluded because they had auras and four of them were excluded because of their use of medication that can affect cerebral blood flow velocity and breath holding index (beta or calcium channel blockers). Our study population consisted of 31 patients with chronic migraine without aura and 29 age- and gender-matched healthy individuals who were not taking any medication. The mean blood flow velocity and breath holding index were measured on both sides from the middle cerebral artery and posterior cerebral artery, with temporal window insonation. The breath holding index for middle cerebral artery and posterior cerebral artery was significantly lower in the migraine group compared to that of the control group (p < 0.05).The vasomotor reactivity indicates the dilatation potential of a vessel, and it is closely related to autoregulation. According to our results, the vasodilator response of cerebral arterioles to hypercapnia was lower in patients with chronic migraine. These findings showed the existence of impairments in the harmonic cerebral hemodynamic mechanisms in patients with chronic migraine. This finding also supports the existing idea of an increased risk of stroke in patients with chronic migraine due to impaired vasomotor reactivity.

Head Position and Cerebral Blood Flow Velocity in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: Patients with acute ischemic stroke (AIS) have impaired vasomotor reactivity, especially in the affected cerebral hemisphere, such that they may depend directly on systemic blood pressure to maintain perfusion to vulnerable ‘at risk' penumbral tissue. As the sitting up position may affect cerebral perfusion by decreasing cerebral blood flow (CBF) in salvageable tissue, positioning AIS patients with their head in a lying flat position could increase CBF through collateral circulation or gravitational force. We wished to quantify the effect of different head positions on mean flow velocity (MFV) by transcranial Doppler ultrasonography (TCD) in AIS patients to assess the potential for benefit (or harm) of head positioning in a clinical trial. Methods: We performed a systematic review and meta-analysis of observational studies with TCD to evaluate differences in cerebral MFV between the lying flat and sitting up head positions in AIS. For each study and each comparison, we obtained the mean value of changes in MFV and its variance. Results: A total of 303 studies were identified, but 298 were excluded for varying reasons; 4 papers met the inclusion criteria and 57 patients were included in the meta-analysis for calculation of the overall mean difference in MFV. We found a significant increase in MFV from a bed angle of 30 to 15° (4.6 cm/s, 95% confidence interval, CI, 2.9-6.2, p < 0.001) and from 30 to 0° (8.3 cm/s, 95% CI 5.3-11.3, p < 0.001) in the affected hemisphere but not on the normal side in AIS patients. Conclusions: In AIS patients, MFV increased significantly in the side affected by the stroke but not in the unaffected side when they were positioned in a lying flat head position at 0 or 15° compared to an upright head position at 30°. The clinical significance of these findings is now undergoing further randomized evaluation in the international multicenter Head Position in Acute Stroke Trial (HeadPoST).

Moderate correlation between breath‐holding and CO2 inhalation/hyperventilation methods for transcranial doppler evaluation of cerebral vasoreactivity

Both CO(2) inhalation followed by hyperventilation and breath-holding have been utilized to measure cerebral vasomotor reactivity (VMR) but their correlation has been poorly studied and understood. A retrospective study was conducted in 143 subjects (62.6 ± 15.8 years old, 64% men) with transcranial Doppler ultrasonography measurement of mean flow velocity (MFV) at baseline, after 30 seconds of breath-holding, and after CO(2) inhalation followed by hyperventilation, in the left and right middle cerebral artery. Breath-holding index (BHI) was calculated as the percentage of MFV increase from baseline per second of apnea. CO(2) inhalation/hyperventilation index (CO(2) /HV) was calculated as the percentage of MFV difference between CO(2) inhalation and hyperventilation. There were 75 carotid arteries with >70% stenosis or occlusion, and 18 middle cerebral arteries with >50% stenosis or occlusion. The mean BHI was 0.93 ± 0.7 and 0.89 ± 0.6, whereas the mean CO(2) /HV was 61 ± 26% and 60 ± 26%, respectively, on the right and left sides. The correlation between BHI and CO(2) /HV was moderate on the right (r = 0.33; p < 0.01) and left sides (r = 0.38; p < 0.01). Multivariate linear regression analysis indicated that age (p = 0.01) and history of stroke (p = 0.007) were associated independently with an impaired VMR on the right as measured by CO(2) /HV. No predictors for impaired VMR by CO(2) /HV on the left and by BHI on either side were found. CO(2) /HV and BHI are only moderately correlated. Further studies are necessary to determine which method more accurately predicts clinical morbidity. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 2012; Published online in Wiley Online Library.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism

Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

Evaluation of cerebral vasomotor reactivity in Parkinson's disease: Is there any association with orthostatic hypotension?

Objective Our aim was to look for a probable relationship between cerebral vasomotor reactivity (VMR) and orthostatic hypotension (OH) in Parkinson's disease (PD). Materials and methods This study was conducted on 44 patients with PD. Assessment of cerebral VMR was performed by means of transcranial Doppler (TCD) of middle cerebral artery (MCA) before and after a vasodilatory stimulus, carbon dioxide test. Moreover, orthostatic hypotension was evaluated. Results OH was presented in 12 (27.3%) Parkinson's patients. The average resting blood flow velocity (BFV) in the MCA was 30.20 (SD = 9.58) cm s −1 which significantly increased to 46.25 (SD = 16.23) cm s −1 after carbon dioxide test ( P < 0.001). Impaired VMR was observed in 15 (34.1%) of the subjects, while it was not associated with the presence of OH ( P = 0.770). Conclusion Evaluation of VMR in patients affected by PD, could assist in early diagnosis of cerebral autonomic dysfunction and prevent its serious consequences prior and more valid to OH.

Long‐term follow‐up of patients with asymptomatic occlusion of the internal carotid artery with good and impaired cerebral vasomotor reactivity

Cerebral hemodynamic status might be prognostic for either the symptomatic or asymptomatic course of carotid occlusive disease. It is determined by evaluating cerebral vasomotor reactivity (VMR). We assessed VMR in asymptomatic patients with total occlusion of the internal carotid artery (ICA) and followed them to evaluate the role of impaired VMR in predicting ischaemic stroke (IS). Thirty-five patients (21 men, mean age ± SD 68 ± 7.5 years) with unilateral asymptomatic ICA occlusion were studied by transcranial Doppler and the Diamox test (intravenous 1.0 g acetazolamide) and followed for 48 months or until reaching the end-points of IS, transient ischaemic attack, or vascular death. VMR% was evaluated by recording the percent differences in peak systolic blood flow velocities in each middle cerebral artery at baseline and after Diamox administration. Based on VMR% calculations, 14 (40%) patients had good VMRs and 21 (60%) had impaired VMRs. The global annual risk of ipsilateral ischaemic events was 5.7%. The annual ipsilateral ischaemic event risk was 1.8% in patients with good VMRs, whilst it was 7.1% in patients with impaired VMRs. An impaired VMR was significantly correlated with ipsilateral IS (Kaplan-Meier log rank statistic, P = 0.04). Our results support the value of VMR assessment for identifying asymptomatic patients with carotid occlusion who belong to a high-risk subgroup for IS. New trials using extracranial-to-intracranial bypass surgery in patients with asymptomatic ICA occlusion and impaired VMRs are warranted.

Metabolic syndrome and impaired vasomotor reactivity: causal relationship or chance association?

Metabolic syndrome and impaired vasomotor reactivity: causal relationship or chance association?

Prognostic impact of microembolic signals in arterial sources of embolism

Sir I read with interest the review by Ritter et al. [3] regarding the prevalence and prognostic impact of microembolic signals (MES) in arterial sources of cerebral embolism. I wish to comment on some important issues related to this review. Emboli originating from an atherosclerotic stenotic plaque are considered to play an important etiological role in subsequent cerebral ischemic events [2], and the detection of MES may help in clinical decision-making, especially in patients previously considered to have asymptomatic arterial stenoses. However, this approach is still not widely accepted and appears to be looking at ‘only one side of the picture.’ Cerebral ischemic events secondary to hemodynamic disturbances (hypoperfusion) in patients with significant stenotic lesions constitute an important clinical group, and these patients can be easily evaluated with transcranial Doppler and assessment of cerebral autoregulation (CA). CA is the inherent ability of the cerebral blood vessels to maintain the blood flow over a wide range of systemic blood pressure and various provocative stimuli [6] and can be assessed by testing the vasomotor reactivity (VMR). Flow velocities obtained in real-time by TCD can reflect cerebral blood flow volume (CBFV), and the velocity changes can be proportionate to the changes in CBFV if certain parameters are known and remain constant (e.g., angle of insonation, perfusion territory, and arterial diameter) and the effect of only one stimulus is observed [5]. Evaluation of VMR to various ‘challenges’ and maneuvers may help in the prognostic assessment of patients with significant stenosis in the cervico-cranial cerebral arteries. Silverstrini et al. [4] demonstrated a significantly higher risk of subsequent cerebral ischemic events in patients with asymptomatic carotid stenosis and having impaired VMR, assessed by breath-holding index. VMR can be easily assessed by monitoring the blood flow velocities (by TCD) during voluntary breath-holding in any intracranial artery distal to the stenosis. Elevation of carbon-dioxide levels in blood during breath-holding is a strong vasodilatory stimulus and results in significant augmentation of flow velocities in the intracranial arteries. However, the arteries distal to the segment with significant stenosis tend to maintain maximal vasodilation and may not dilate further in response to hypercapnia, reflected by a blunted response in the blood flow velocities. The response may be further affected, in some cases, due to ‘intracranial steal phenomenon’ known as ‘reversed Robin Hood syndrome’ [1]. I propose that, in addition to the MES monitoring, patients with hemodynamically significant stenosis in the cervical or intracranial cerebral arteries should be evaluated for VMR by TCD. Assessment of VMR in the arterial segments distal to the atherosclerotic segment would reveal, at least to some extent, the ‘other side of the picture’ and help in better understanding of cerebral hemodynamics and the pathogenic mechanisms of cerebral ischemia in these patients. Well-designed prospective studies would, however, be needed to test the feasibility and efficacy of this approach in clinical decision-making.

Reperfusion normalizes motor activation patterns in large‐vessel disease

Hemodynamic impairment in one hemisphere has been shown to trigger ipsilateral motor activation in the opposite hemisphere on functional imaging. We hypothesized that reversing the hypoperfusion would normalize the motor activation pattern. We studied four patients with high-grade stenosis and impaired vasomotor reactivity (VMR) but no stroke. Functional magnetic resonance imaging motor activation pattern before and after VMR normalization was compared with seven healthy control subjects scanned at an interval of 3 months using voxel-wise statistical parametric maps and region of interest analysis. Subjects performed a repetitive hand closure task in synchrony with 1Hz metronome tone. We used repeated-measures analysis of variance to compute the interaction between group (patients/control subjects) and time by obtaining the average blood oxygen level dependent signal of three motor regions of interest in each hemisphere. Two patients normalized their VMR after spontaneous resolution of dissection, and two after revascularization procedures. Both voxel-wise statistical maps and region of interest analysis showed that VMR normalization was associated in each case with a reduction in the atypical activation in the hemisphere opposite to the previously hypoperfused hemisphere (p < 0.001). In the presence of a physiological stressor such as hypoperfusion, the brain is capable of dynamic functional reorganization to the opposite hemisphere that is reversible when normal blood flow is restored. These findings are important to our understanding of the clinical consequences of hemodynamic failure and the role of the ipsilateral hemisphere in maintaining normal neurological function.

Long term follow-up of unilateral occlusion of the internal carotid artery including repeated tests of vasomotor reactivity by transcranial Doppler

Background: Early study on pathological flow pattern in the ophthalmic artery (OA), connected with impaired vasomotor reactivity (VMR) and low pulsatility index (PI) in the anterior cerebral artery (ACA) on the occluded side, suggested collateral exhaustion. We undertook this study to evaluate whether the occurence of new strokes is predicted by special haemodynamic features.Method: A total of 27 patients (22 men and five women), aged 63 ± 15 years (mean ± SD) with longstanding occlusion of the internal carotid artery (ICA), confirmed by duplex scanning were studied. They had minimal neurological deficit and were followed-up for mean 4.3 ± 1.8 (mean ± SD) years by repeated clinical and 3-D transcranial Doppler (3-D TCD) examinations with azetazolamide test of vasomotor reactivity (VMR).Results: During follow-up, seven patients had new strokes (five minor strokes and two major ones), two ipsilateral and four contralateral to the ICA occlusion and one in the posterior circulation. Four patients died, All patients experiencing a new stroke had previous symptoms and pathological flow patterns in the OA, i.e retrograde or isoelectric flow were noted in six of them. One patient with contralateral stroke experienced occlusion of the ICA located above the origin of the OA with anterograde flow; otherwise none of 11 patients with anterograde flow had a new stroke (p<0.05, Fisher exact text). During the follow-up, the initial mean velocity (MV) in the middle cerebral artery (MCA) on the occluded side in six patients with a new stroke in the anterior circulation, was 26.83 ± 10.50 cm/s, which was significantly different from that of patients without a new stroke (45.80 ± 12.8 cm/s) (p<0.01). MV in the ICA on the non-occluded side at the last examination was greater than that at the first examination (p<0.05) and increased after the use of acetazolamide only on this side (p<0.05), while PI decreased bilateraly (p<0.001 and 0.05). Resting MV both in the MCA on the occluded and ACA on the non-occluded side slightly decreased, while MV in the posterior cerebral artery (PCA) increased on the occluded side (p<0.083) compared with that at the start of the follow-up. VMR in the ACA decreased slightly both on the non-occluded and occluded side (Δ-6.9 and Δ-5.3 respectively), while impaired VMR ≤ 11% was not significantly connected with new strokes.Conclusion: During the follow up, new strokes had appeared on both sides and in vertebrobasilar territory and were connected with pathological flow pattern in the OA and low MV in the MCA at the first examination.

Hypoperfusion without stroke alters motor activation in the opposite hemisphere

To specifically investigate the effect that large-vessel disease may have on cortical reorganization, we used functional magnetic resonance imaging to study patients with unilateral hemispheric hypoperfusion and impaired vasomotor reactivity from critical internal carotid or middle cerebral artery disease but without stroke. We hypothesized that when these patients used the hand contralateral to the hypoperfused hemisphere they would show unique activation in motor-related areas of the normally perfused hemisphere, that is, ipsilateral activation. We found that normal performance of two motor tasks was associated with increased ipsilateral hemispheric activation in the patients compared with age-matched controls. In addition, although task difficulty had an effect on ipsilateral activation, the increased ipsilateral activation seen in patients was not dependent on task difficulty. Our findings demonstrate that hemodynamic compromise alone is sufficient to cause atypical ipsilateral activation. This activation may serve to maintain normal motor performance.