[Telemedicine in stroke-pertinent to stroke care in Germany]. / Telemedizin in der Schlaganfallversorgung ­ versorgungsrelevant für Deutschland.

BACKGROUND AND OBJECTIVE: Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. METHODS: The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. RESULTS: Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1-3) as well as 225 cooperating hospitals (per network: median 9, IQR 4-17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319-2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6-14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5-8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. CONCLUSION: Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.

Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Effects of anti-inflammatory vagus nerve stimulation in endotoxemic rats on blood and spleen lymphocyte subsets.

BACKGROUND: Anti-inflammatory cytokine effects of vagus nerve stimulation in sepsis syndromes are well established. Effects on immune cells are less clear. Therefore, we studied changes in peripheral and spleen leukocyte subsets in an endotoxic rat sepsis model. METHODS: Ventilated and sedated adult male SD rats received 5 mg/kg b.w. lipopolysaccharide intravenously to induce endotoxic sepsis. Controls and a group with both-sided vagotomy were compared to animals with both sided vagotomy and left distal vagus nerve stimulation. 4.5 h after sepsis induction immune cell counts and types in the peripheral blood and spleen were determined [T-lymphocytes (CD3+), T-helper cells (CD3+ CD4+), activated T-helper cells (CD3+ CD4+ CD134+), cytotoxic T-cells (CD3+ CD8+), activated cytotoxic T-cells (CD3+ CD8+ CD134+), B-lymphocytes (CD45R+ CD11cneg-dim), dendritic cells (CD11c+ OX-62 +), natural killer cells (CD161+ CD3neg) and granulocytes (His48 +)] together with cytokine and chemokine plasma levels (IL10; IFN-g, TNF-a, Cxcl5, Ccl5). RESULTS: Blood cell counts declined in all LPS groups. However, vagus nerve stimulation but not vagotomy activated cytotoxic T-cells. Vagotomy also depleted natural killer cells. In the spleen, vagotomy resulted in a strong decline of all cell types which was not present in the other septic groups where only granulocyte numbers declined. CONCLUSION: Vagotomy strongly declines immune cell counts in the septic spleen. This could not be explained by an evasion or apoptosis of cells. A marginalisation of spleen immune cells into the peripheral microcirculation might be therefore most likely. Further studies are warranted to clear this issue.

[Near-infrared spectroscopy in sepsis therapy : predictor of a low central venous oxygen saturation]. / Nahinfrarotspektroskopie in der sepsistherapie : prädiktor für eine erniedrigte zentralvenöse sauerstoffsättigung.

BACKGROUND: Early goal-directed hemodynamic optimization has become a cornerstone of sepsis therapy. One major defined goal is to achieve adequate central venous oxygen saturation (SO(2)). This study aimed to investigate the correlation between central venous SO(2) and frontal cerebral near-infrared spectroscopy (NIRS) measurement in patients with severe sepsis and septic shock. The NIRS method provides non-invasive measurement of regional oxygen saturation (rSO(2)) in tissues approximately 2 cm below the optical NIRS sensors which depends on arterial, capillary and venous blood. Thus this system gives site-specific real-time data about the balance of oxygen supply and demand. METHODS: This was a secondary analysis from a prospective study of surgical intensive care (ICU) patients in the early phase of severe sepsis or septic shock. Bilateral cerebral rSO(2), central venous SO(2), arterial oxygen saturation (S(a)O(2)) and other surrogate parameters of oxygen supply, such as hemoglobin, partial pressure of oxygen and oxygen content in arterial blood were recorded. RESULTS: A total of 16 ICU patients (4 women, median age 65.5 years) were included in the study. As sepsis focus an intra-abdominal infection was detected in 62.5 % of patients, severe pneumonia was determined in 31.3 % and skin and soft tissue infections were recognized in 12.5 %. At study inclusion 50 % of patients had septic shock, the median sequential organ failure assessment (SOFA) score was 10.2 (interquartile range 5.25-8.75) and the median acute physiology and chronic health evaluation II (APACHE II) score was 26 (range 23.25-29.75). Mortality at day 28 was 37.5 %. Minimum rSO(2) (median 58) and right-sided rSO(2) (median 58) values showed a significant correlation in the analysis of receiver operating characteristics (area under the curve 0.844, p= 0.045). A central venous SO(2)< 70 % was indicated by rSO(2)< 56.5 with sensitivity and specificity of 75 % and 100 %, respectively. CONCLUSIONS: Cerebral NIRS could provide a fast and easily available side effect-free monitoring that could be used in addition to established procedures for goal-directed treatment in the early phase of sepsis. Further studies should be made in a larger population to verify the correlation found and to investigate the impact of NIRS-directed resuscitation treatment in early sepsis.

[Obstructive sleep apnea and stroke]. / Obstruktive Schlaf-Apnoe und Schlaganfall.

More than half of the patients hospitalised with stroke suffer from sleep-disordered breathing and 5 - 10 % of patients with newly diagnosed obstructive sleep apnea (OSA) have a history of stroke. Epidemiological studies have shown that untreated OSA is an independent risk factor for stroke. Various pathophysiological mechanisms may contribute to the development of stroke in these patients (i. e., OSA-associated arterial hypertension, atherosclerosis, atrial fibrillation, paradoxical embolism through a patent foramen ovale and disturbed cerebrovascular reactivity). Co-existent OSA has a negative impact on both the recovery of neurological functions and the survival of patients with stroke. On the other hand, CPAP therapy has beneficial effects on the incidence and recurrence of stroke in OSA and also on the clinical outcome of those patients who are victims of stroke.

[Clinical neurological diagnosis of sepsis-associated delirium]. / Klinisch-neurologische Diagnostik des sepsisassoziierten Delirs.

Sepsis is a frequent emergency and an acute disease which is still highly lethal. Due to an early involvement of the brain in terms of a sepsis-associated delirium the neurologist plays an important role in the early diagnosis of the interdisciplinary disease. The following review details the main diagnostic aspects of a sepsis-associated delirium.

Impaired neurovascular coupling in ischaemic stroke patients with large or small vessel disease.

BACKGROUND AND PURPOSE: There is limited data of neurovascular coupling on stroke patients, especially on comparison of different etiologies. We aim to test the hypothesis that patients with small vessel disease (SVD) are impaired on neurovascular coupling rather than stroke patient with large intracranial artery stenosis (LIAS), because small vessel is more associated with microcirculatory function. To assess microcirculatory integrity of stroke patients, we performed a functional transcranial Doppler test using a standardized visual stimulation test. METHODS: The neurovascular coupling was measured in the asymptomatic occipital cortex in ischaemic stroke patients with LIAS, SVD, and healthy elder controls. Bilateral posterior cerebral arteries were monitored to measure evoked flow velocity during resting and visual stimulation phase. Peak systolic flow velocity responses were recorded, and time course of hemodynamic response was modeled according to a control system analysis with the parameters gain, natural angular frequency, attenuation, and rate time. RESULTS: Reproduced for both sides, the functionally induced flow velocity changes (gain) were significantly lower in LIAS and SVD compared with controls (P < 0.001). Reductions in both stroke groups were in the same order. Neurovascular coupling in LIAS group did not show difference at the side of vessel stenosis compared with non-stenosis side or at different stenotic degrees. CONCLUSIONS: Interestingly, both LIAS and SVD showed an uncoupling of the blood supply of active neurons. This points to an additional small vessel dysfunction in patients with LIAS.

A simultaneous EEG and transcranial Doppler technique to investigate the neurovascular coupling in the human visual cortex.

Due to lacking energy stores, high energy consumption and dependency on a strict aerobic glycolysis, the brain is very dependent on an adequate blood supply of active neurons. Adequate regulation of the functionally induced local cerebral blood flow is assured by neurovascular coupling. Our understanding of its role in different disease processes has improved considerably in the last few years. Consequently, a diagnostic tool is needed which allows an easy and cost-effective investigation of the coupling in clinical conditions. A combined EEG and Doppler technique might be suitable in this regard. This review gives a short overview of the neurophysiological background and the techniques, before validation studies and first clinical applications are addressed.

Severity of coronary artery disease but not degree of coronary stenosis is correlated to cerebrovascular reactivity.

BACKGROUND: A decade difference in peak incidences of coronary and cerebral ischemia assumes a protection of the brain vasculature. Therefore, we hypothesize that early indicators of cerebrovascular disease such as parameters of the neurovascular coupling show a higher correlation to coronary artery disease than morphologic parameters. METHODS: Stenotic degree (%) of coronary arteries (RCA, LCA, LAD, RCX) was determined together with the Gensini score by angiography in 96 patients (80 men; 62 +/- 10 years), which were grouped according to disease severity (sclerosis, 1-vessel disease (VD), 2-VD, 3-VD). Presence of internal carotid artery stenosis and left ventricular ejection fraction (LVEF) were established with duplex sonography. Resting and visually evoked hemodynamic responses were measured with transcranial Doppler ultrasound in both posterior cerebral arteries and expressed in terms of control system parameters. These were gain, natural frequency, attenuation, and rate time. Group differences and correlations between stenosis and parameters of vasoreactivity were tested. RESULTS: Groups differed in stenotic degree of coronary arteries, Gensini score, LVEF, carotid artery stenosis, resting flow velocity, and evoked responses (gain, p < 0.005; attenuation, p < 0.05). Stenosis of each coronary artery and LVEF were correlated to carotid artery stenosis but no association was found to cerebrovascular parameters. Only severity of coronary artery disease and the Gensini score were associated with disturbed cerebrovascular reactivity. Carotid artery stenosis was associated with decreased cerebrovascular parameters (attenuation, p < 0.05; rate time, p < 0.01). CONCLUSIONS: Although atherosclerosis is a systemic disease our data support concepts of a heterogeneous distribution of the disease indicating protection of brain vessels.

Autoregulative function in the brain in an endotoxic rat shock model.

OBJECTIVE AND DESIGN: Autoregulative function in the brain gets relevant in hypodynamic conditions of a sepsis syndrome. We investigated the temporal pattern and dose dependent effects of LPS-induced shock on autoregulative function in rats. MATERIAL AND SUBJECTS: Chloralose-anesthetized and mechanically ventilated male CD-rats (n = 30). TREATMENT: Animals were subjected to vehicle, 1 or 5 mg/kg b.w. lipopolysaccharide (LPS) from E. coli given intravenously. METHODS: Autoregulative function was tested repeatedly with a carotid compression technique assessing the transient hyperemic response ratio (THRR) in the cortex with laser Doppler flowmetry up to 270 min. THRR data from exsanguination experiments served as controls. RESULTS: Despite lower blood pressure levels in the high dose group (control: 114 +/- 7 mmHg; 1 mg/kg LPS group: 82 +/- 16 mmHg; 5 mg/kg LPS group: 62 +/- 16 mmHg; p < 0.05) progressive cerebral hyperemia occurred similarly in both groups. Compared to exsanguinations experiments autoregulative compensation for lower blood pressure levels was lacking in the high LPS dose group at the end of experiments. CONCLUSIONS: Cerebral autoregulation was affected by LPS-induced shock supporting the notion of vasoregulative failure in endotoxic shock.

LPS-induced endotoxic shock does not cause early brain edema formation - an MRI study in rats.

OBJECTIVE AND DESIGN: Early microcirculatory failure is assumed as a key factor in the development of a septic encephalopathy. However, brain edema is also a common finding in sepsis syndromes possibly interfering with the vasoregulative mechanisms of the brain. We assessed the occurrence of brain edema in a rat model of endotoxic shock. MATERIAL AND SUBJECTS: Eleven mechanically ventilated male CD-rats. TREATMENT: Intravenous application of 5 mg/kg LPS (n = 8) or vehicle (n = 3). METHODS: Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on cerebral MRI at baseline and repeatedly for up to 3.5 h after LPS-injection. Change in blood pressure was compensated with norepinephrine. Brain water content was quantified using the wet/dry method. RESULTS: All LPS-treated rats developed endotoxic shock. No significant difference in T2RT or ADC was detectable before and after LPS-injection (T2RT: baseline 60.33 +/- 1.21; after 3.5 h 60.15 +/- 0.59; ADC: baseline 6.86 +/- 0.51; after 3.5 h 6.75 +/- 0.33). Post-mortem analysis did not indicate a difference in brain water content between septic and non-septic animals. CONCLUSIONS: Reports of early microcirculatory failure seem not to be related to the occurrence of early (< or =3.5 h) brain edema.

Sildenafil improves dynamic vascular function in the brain: studies in patients with pulmonary hypertension.

BACKGROUND: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. METHODS: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. RESULTS: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. CONCLUSIONS: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.

Influence of stimulus duration on the neurovascular coupling response.

AIM: The neurovascular coupling mechanism adapts cerebral blood flow in accordance with cortical activity. It reacts rapidly, reliably and in a finely tuned manner. Therefore, the question emerged at to whether this might be a linear mechanism. Recently, non-linearity was concluded from different time curves of flow regulation, resulting from stimulation of varying duration. Short lasting stimulation resulted in a peak response, whereas longer stimulation led to a peak and plateau characteristic of flow response. We suggest the different responses may be caused by dynamic properties of the coupling. METHOD: A functional transcranial Doppler test was performed using a visual stimulation paradigm in 10 healthy volunteers (age 25.8 +/- 0.5 years, 7 men). Two tests with different stimulus duration were used (20 s versus 40 s). The short test was known to result in the dynamic pattern, and the long test in the static phase of flow regulation. The data from the long test were evaluated according to a control system approach. The resultant model was used to calculate data of an assumed 20 s stimulation. A paired t-test was used to compare the measured and calculated flow data for the short stimulation test. RESULTS: The flow velocity responses were identical when comparing the first 20 s of stimulation. At the termination of stimulation in the short test, flow velocity returned to baseline leading to a peak response, whereas flow velocity stabilised at a constant level above baseline in the long stimulation paradigm, resulting in the peak and plateau characteristic. CONCLUSION: The different flow responses due to different stimulus duration are caused by dynamic properties of the coupling mechanism and are not indicative of non-linearity.

Abnormal regulation of maternal cerebral blood flow under conditions of gestational diabetes mellitus.

AIM: Gestational diabetes mellitus is a prediabetic state leading to endothelial dysfunction and altered organ perfusion. Under normal conditions cerebral blood flow is closely coupled to cortical activity, to which it rapidly adjusts. On the basis of this so-called neurovascular coupling we evaluated the influence of a gestational diabetic state on endothelium-dependent vasoregulative properties of this mechanism. METHOD: A functional transcranial Doppler test performed during visual stimulation was used to measure vascular reactivity. Peak systolic and end-diastolic flow velocity response from 20 non-pregnant (age 27 +/- 6 y), 31 healthy pregnant women (31 +/- 6 y; 31 +/- 4 gestational week) and 30 women with gestational diabetes (32 +/- 5 y; 34 +/- 4) were separately evaluated according to a control system approach. All women did not show any vascular risk factors prior to pregnancy. RESULTS: Comparison of resting blood flow velocity and the control system parameters of gain, attenuation, rate time and natural frequency, showed a consistent and significant difference in the parameter "attenuation" for the peak systolic data (0.55 +/- 0.18 vs. 0.44 +/- 0.1 and 0.45 +/- 0.11, p < 0.01) as well as end-diastolic (0.61 +/- 0.23 vs. 0.49 +/- 0.2 and 0.5 +/- 0.14, p < 0.05) figures (mean +/- SD of value from women with gestational diabetes vs. non-pregnant and healthy pregnant women, significance level). No differences were found between non-pregnant and normal pregnant women for the neurovascular coupling mechanism. CONCLUSIONS: Gestational diabetes mellitus results in endothelial dysfunction which can be measured in a non-invasive, painless and easy manner by a transcranial Doppler test.

A control system approach for evaluating somatosensory activation by laser-Doppler flowmetry in the rat cortex.

Coupling between functional cortical activity and blood flow is a regulatory principle that adjusts the supply of substrates to the metabolic needs of the tissue. The flow response is usually expressed as the maximum increase over baseline; control system analysis allows the description of the entire time course and the main dynamic features of the regulative principle. In chloralose-anesthetized rats, forepaws were stimulated by trains of electric pulses of 0.3 or 5 ms duration. Blood flow was recorded in the contralateral somatosensory cortex by laser-Doppler flowmetry and correlated with the amplitude of primary somatosensory evoked potentials (SEP). Changes were analyzed by a control system approach. Pulses of 0.3 or 5 ms evoked SEPs of similar amplitude, whereas flow responses differed: 0.3 ms pulses led to a peak and plateau characteristic, 5 ms pulses evoked a plateau characteristic. The flow response evoked by 0.3 ms pulses can be modeled mathematically by an initial feedforward regulative principle followed after some delay by feedback controlled flow stabilization, whereas 5 ms pulses lack the feedforward component. The absence of an electrophysiological difference points to a dissociation between electrophysiological and hemodynamic responses and may be of importance for the understanding of flow coupling.

Contrast media effect on cerebral blood flow regulation after performance of cerebral or coronary angiography.

OBJECTIVE: The immediate hemodynamic effects of contrast agents are well documented. Less is known about their longer-lasting effects. We investigated the later effect of iopromide on the neurovascular coupling mechanism after the performance of cerebral or coronary angiography. Neurovascular coupling is a fine-tuned and reliable mechanism adapting cerebral blood flow to cortical activity. When performing a visual stimulation and measuring the resultant flow velocity change in the posterior cerebral artery transcranial Doppler has been used to determine vascular integrity. METHODS: The visually evoked blood flow velocity response in the posterior cerebral artery was measured with transcranial Doppler before, 1-2 h after and the day after angiography. The overshoot of the flow velocity response and the stable flow velocity level at the end of the stimulation phase were used to compare the different conditions. RESULTS: A significantly diminished overshoot was found 1-2 h after angiography only in patients undergoing cerebral angiography. The stable blood flow velocity levels at the end of the stimulation phase remained unchanged in all cases. CONCLUSIONS: Our finding demonstrates effects of contrast media on dynamic blood flow regulation of the cerebral vasculature 1-2 h after application of direct contrast agent suggesting a possible concentration effect of the contrast agent. However, since the relative blood flow velocity increase under stable blood flow conditions remained constant, this dynamic alteration does not cause a reduction in cerebral blood flow.

Effect of heart rate on regulative features of the cortical activity-flow coupling.

OBJECTIVE: Heart rate plays an important role in compensatory conditions of arterial pressure changes. Very little information, however, exists on its role in the dynamic adjustment of stimulated organ perfusion. We studied the influence of heart rate on the activity-flow coupling mechanism which adapts local cerebral blood flow in accordance with cortical activity. Since it does not affect heart rate or arterial blood pressure by itself, the commonly observed heart rate variability in test conditions was used to compare the flow response between different heart rate groups. For evaluation under stable heart rate conditions we performed a short test paradigm with a transcranial Doppler technique with the necessary high time resolution. METHODS: 168 healthy young volunteers (24 +/- 3 years of age) were grouped according to their heart rate in decade steps from 60 to 100 beats/min (mean: 82 +/- 9 beats/min). The visually evoked flow velocity responses in the posterior cerebral artery were evaluated according to a control system approach. Peak systolic and end diastolic data were evaluated separately. RESULTS: A correlation analysis between heart rate and baseline flow velocity as well as each of the control system parameters, i.e. gain, attenuation, rate time and natural frequency, revealed no significance. The flow responses did not differ among the heart rate groups as concluded from an ANOVA test. DISCUSSION: The increase in heart rate and the possible stress factors responsible for this seem to be of no relevance in regulative features of the activity-flow coupling. The almost identical time course of flow velocity responses among the groups showing a heart rate difference of up to 50% indicates an integrative principle in flow regulation supporting simplified concepts of flow adaptation.

Doppler investigation of within-session reproducibility in a visual stimulation task to assess the volunteer-dependent variation.

OBJECTIVE: In functional magnetic resonance imaging (MRI) studies in humans the tightness of activity-flow coupling was questioned due to a notable within-session variability of the signals obtained. To differentiate between moments of volunteer-dependent or technique-inherent variation in hemodynamic MRI measurements a method with a low technique-inherent variation is needed. Therefore, and because temporal features might also be of some relevance, we used the transcranial Doppler method. METHODS: In 22 healthy volunteers the flow-velocity response to a visual stimulation task was evaluated. Conditions of 20 s of eye closure were altered with 40 s of silent reading, repeated 10 times. Averaged individual flow-velocity responses were evaluated from conditions of 40 s of stimulation and a 5-second time interval prior to the beginning of stimulation. The averaged data were subtracted from each single recording to calculate the mean squared differences (MSD). Statistical evaluation was performed according to a two-way ANOVA for repeated measures. To obtain additional qualitative data of the flow response, the individual flow curves were evaluated according to a control system approach specifying a second-order linear model. RESULTS: The coefficient of variation (COV) of the within-session MSD was 7% for the stimulation phase and 2.9% for the resting phase, whereas the respective COVs were 15 and 8.1% for the interindividual MSDs. The interindividual COVs of control system parameters ranged from 3.6 to 7.6%. The ANOVA resulted in a significant (p < 0.003) difference for the MSD values between stimulation conditions, whereas the test repetition (p = 0.55) and the test for an interaction of repetition and stimulation condition (p = 0.54) revealed no significance. DISCUSSION: Confirming the notion of a tight coupling between cortical activity and cerebral blood flow and being indicative of a low technique-inherent variation, we found a high within-session reproducibility in a functional Doppler test.

Neurovascular coupling remains unaffected during normal aging.

BACKGROUND AND PURPOSE: During normal aging, the cerebral autoregulation mechanism and the CO2-induced cerebral reserve capacity remain unaffected. This led to the suggestion of a wide compensatory range of mechanisms responsible for the cerebral blood flow regulation. The authors investigated the neurovascular coupling mechanism for age-related changes. Because several authors criticized the comparison between higher and younger age groups, the current authors restricted their study on volunteers between 10 and 60 years. METHODS: Twenty healthy volunteers in the age group of 10 to 20, 20 to 40, and 40 to 60 each without cerebrovascular risk factors were enrolled in this study; they were aged 16.3 +/- 3.4 SD years (9 boys), 32.7 +/- 2.3 SD years (9 men), and 53.1 +/- 5.3 SD years (10 men). A functional transcranial Doppler test was performed using a visual stimulation paradigm. The resultant flow velocity changes in the posterior cerebral artery were analyzed using a control system approach. Resting flow velocity and each of the control system parameters, which were time delay, attenuation, natural frequency, rate time, and gain, were compared between groups statistically. RESULTS: Control system parameters remained statistically unchanged between groups, whereas the resting flow velocity decreased significantly by age. CONCLUSIONS: The neurovascular coupling mechanism seems to be unaffected by moderate aging as estimated by Doppler parameters. Vasoregulative dysfunction in patients at vascular risk is more likely to be caused by the risk factor rather than by age.

Effects of acute hyperhomocysteinemia on the neurovascular coupling mechanism in healthy young adults.

BACKGROUND AND PURPOSE: Hyperhomocysteinemia is a vascular risk factor that infers with the nitric oxide signaling pathway of endothelial vasoregulation. Most investigations in young healthy humans on the peripheral vasculature using a standardized methionine challenge demonstrated altered vascular reactivity. In contrast, the cerebral autoregulation mechanism was shown to be unaffected by the same methionine load. To obtain additional insight into the compensatory range of the cerebral vasculature during a methionine challenge, we tested the neurovascular coupling mechanism that adjusts cerebral blood flow in accordance with cortical activity. METHODS: Fifteen healthy young adults (age, 24.7+/-2.3 years; 7 men) were tested with a functional transcranial Doppler test before and 3, 8, and 24 hours after administration of placebo, 20 mg folic acid, 20 mg folic acid and 0.1 g/kg body weight L-methionine, or L-methionine alone. Evoked blood flow response was evaluated according to a control system approach. Plasma concentrations of homocysteine, resting blood flow velocities, and control system parameters of flow velocity change were compared for each time point using a multiple analysis of variance test. RESULTS: Homocysteine levels increased significantly compared with baseline (before, 7.6+/-1.9 micromol/L; 3 hours, 22.2+/-6.0 micromol/L [P<0.0001]; 8 hours, 27.9+/-8.6 micromol/L [P<0.0001]; 24 hours, 12.6+/-7.8 micro mol/L [P=NS]). Resting flow velocities and control system parameters remained statistically nonsignificant. CONCLUSIONS: Compared with the peripheral vasculature, the regulatory mechanisms controlling adequate cerebral blood flow appear to have a wider compensatory range. This is concluded from statistically nonsignificant results comparing the vascular reactivity in young adults undergoing a standardized methionine challenge. Our data confirm indirectly the reports of high concentrations of homocysteine needed to affect the cerebral vasculature in animal experiments.