Neurovascular Coupling In Patients Research Articles

Associations of neurovascular dysfunction with inner retinal layer thickness in non‐proliferative diabetic retinopathy

Aims/Purpose: Neurovascular dysfunction and inner retinal layer thinning are among the earliest detectable retinal changes in diabetes, and both worsen during development and progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyse associations between the retinal functional hyperaemic response and thickness of the individual neuroretinal layers in eyes with non‐proliferative DR.Methods: Thirty patients with Type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non‐proliferative DR and 14 healthy subjects were included in this cross‐sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyser. Individual retinal layer thickness in the macula was analysed from spectral domain optical coherence tomography.Results: Flicker light‐induced vessel dilation was significantly reduced in diabetes patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010) and inner plexiform layer thickness (r = 0.40, p = 0.027), and negatively with haemoglobin A1c (HbA1c) levels (r = −0.41, p = 0.023) and age (r = −0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only HbA1c (p = 0.027, β = −0.40) and GCL thickness (p = 0.030, β = 0.39) remained significantly associated with the vascular flicker light response.Conclusions: The results indicate that thinner GCL and worse glycaemic control both contribute to reduced neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

Altered Neurovascular Coupling in Patients With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS): A Combined Resting-State fMRI and Arterial Spin Labeling Study.

Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear. To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL). Prospective. Twenty-four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. 3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. 2 TECHNICAL EFFICACY: Stage 1.

Neurovascular coupling in severe aortic valve stenosis.

Aortic stenosis (AS) is characterized by obstruction of blood outflow from the left ventricle, which can impair target organ perfusion such as the brain. We hypothesized that hemodynamic changes in AS may lead to dysfunction of cerebral blood flow regulatory mechanisms. The aim of our study was to evaluate neurovascular coupling in patients with AS by Transcranial Doppler ultrasonography. Neurovascular coupling was assessed using visually evoked cerebral blood flow velocity responses (VEFR) calculated as relative blood flow velocity changes in the posterior cerebral artery upon visual stimulation. We analyzed peak systolic, mean and end diastolic VEFR in 54 patients with severe AS and 43 controls in 10 consecutive cycles of visual stimulation. Repeated-measures ANOVA test was used to compare cerebral hemodynamic data by group. Patients with AS had significantly higher peak systolic (12.9%±5.6% and 10.5%±4.5%; p=.009) and mean VEFR (14.4%±5.8% and 12.2%±4.9%; p=.021) compared to controls, whereas only a tendency for higher end diastolic VEFR was observed (16.7%±6.9% and 14.4%±6.2%; p=.061). We have shown for the first time that patients with severe AS exhibit higher VEFR than controls indicating dysregulation of neurovascular coupling, which can be one of the factors contributing to development of cognitive decline.

Altered resting-state neurovascular coupling in patients with pontine infarction

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neurovascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.

Altered neurovascular coupling in patients with vascular cognitive impairment: a combined ASL-fMRI analysis.

This study aims to examine the role of neurovascular coupling (NVC) in vascular cognitive impairment (VCI) by investigating the relationship between white matter lesion (WML) burden, NVC, and cognitive deficits. Additionally, we aim to explore the potential of NVC as a tool for understanding the neural mechanisms underlying VCI. This study included thirty-eight small vessel disease cognitive impairment (SVCI) patients, 34 post-stroke cognitive impairment (PSCI) patients, and 43 healthy controls (HC). Comprehensive assessments, including neuroimaging and neuropsychological testing, were conducted to evaluate cognitive function. WML burden was measured and correlated with NVC coefficients to examine the relationship between white matter pathology and NVC. Mediation analysis was employed to explore the link relationship between NVC, WML burden, and cognitive function. The present study showed that NVC was significantly reduced in the SVCI and PSCI groups compared with HCs at both whole-brain and brain region level. The analysis revealed notable findings regarding NVC in relation to WML burden and cognitive function in VCI patients. Specifically, reduced NVC coefficients were observed within higher order brain systems responsible for cognitive control and emotion regulation. Mediation analysis demonstrated that NVC played a mediating role in the relationship between WML burden and cognitive impairment. This study reveals the mediating role of NVC in the relationship between WML burden and cognitive function in VCI patients. The results demonstrate the potential of the NVC as an accurate measure of cognitive impairment and its ability to identify specific neural circuits affected by WML burden.

Altered coupling of resting-state cerebral blood flow and functional connectivity in Meige syndrome.

Meige syndrome (MS) is an adult-onset segmental dystonia disease, mainly manifested as blepharospasm and involuntary movement caused by dystonic dysfunction of the oromandibular muscles. The changes of brain activity, perfusion and neurovascular coupling in patients with Meige syndrome are hitherto unknown. Twenty-five MS patients and thirty age- and sex-matched healthy controls (HC) were prospectively recruited in this study. All the participants underwent resting-state arterial spin labeling and blood oxygen level-dependent examinations on a 3.0 T MR scanner. The measurement of neurovascular coupling was calculated using cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations across the voxels of whole gray matter. Also, voxel-wised analyses of CBF, FCS, and CBF/FCS ratio images between MS and HC were conducted. Additionally, CBF and FCS values were compared between these two groups in selected motion-related brain regions. MS patients showed increased whole gray matter CBF-FCS coupling relative to HC (t = 2.262, p = 0.028). In addition, MS patients showed significantly increased CBF value in middle frontal gyrus and bilateral precentral gyrus. The abnormal elevated neurovascular coupling of MS may indicate a compensated blood perfusion in motor-related brain regions and reorganized the balance between neuronal activity and brain blood supply. Our results provide a new insight into the neural mechanism underlying MS from the perspective of neurovascular coupling and cerebral perfusion.

Altered cerebral neurovascular coupling in medication-overuse headache: A study combining multi-modal resting-state fMRI with 3D PCASL.

Structural and functional changes in the brain have been identified in individuals with medication-overuse headache (MOH) using MRI. However, it has not been clearly established whether neurovascular dysfunction occurs in MOH, which could be elucidated by examining neurovascular coupling (NVC) from the viewpoints of neuronal activity and cerebral blood flow. The aim of this study was to investigate potential alterations in NVC function of the brain in individuals with MOH using resting-state functional MRI (rs-fMRI) and 3D pseudo-continuous arterial spin labeling (3D PCASL) imaging techniques. A total of 40 patients with MOH and 32 normal controls (NCs) were recruited, and rs-fMRI and 3D PCASL data were obtained using a 3.0 T MR scanner. Standard preprocessing of the rs-fMRI data was performed to generate images representing regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC); cerebral blood flow (CBF) images were generated using 3D PCASL sequence data. These functional maps were all normalized into Montreal Neurological Institute (MNI) space, and NVC was subsequently determined on the basis of Pearson correlation coefficients between the rs-fMRI maps (ReHo, fALFF, and DC) and CBF maps. The statistical significance of differences between the MOH and NC groups in terms of NVC in different brain regions was established via Z-test. Further analysis was performed to examine correlations between NVC in the brain regions with NVC dysfunction and clinical variables among patients with MOH. NVC mainly presented a negative correlation in patients with MOH and NCs. No significant difference between the two groups was detected in terms of average NVC over the entire gray matter area. However, several brain regions with significantly decreased NVC in patients with MOH compared to NCs were identified: the left orbital region of the superior frontal gyrus, the bilateral gyrus rectus, and the olfactory cortex (P < 0.05). A correlation analysis revealed that the DC of the brain regions with NVC dysfunction was significantly positively correlated with disease duration (r = 0.323, P = 0.042), and DC-CBF connectivity was negatively correlated with VAS score (r = -0.424, P = 0.035). The current study demonstrated that cerebral NVC dysfunction occurs in patients with MOH, and the NVC technique could function as a new imaging biomarker in headache research.

Altered Neurovascular Coupling in Patients with Chronic Myofascial Pain

Despite previous reports on cerebral structures and functional connectivity in patients with myofascial pain (MFP), it is not clear whether alterations in neurovascular coupling occur in these patients. We analyzed the coupling between resting-state cerebral blood flow (CBF) and functional connectivity strength (FCS) for observation of neurovascular coupling in patients with chronic MFP. Observational study. University hospital. Resting-state functional magnetic resonance imaging and arterial spin labeling were performed in 23 patients with chronic MFP and 23 healthy controls (HC) for the calculation of FCS and CBF. The whole-brain gray matter CBF-FCS correlations and CBF/FCS ratios of the various voxels of the 2 groups were subsequently compared. Compared with the HC, the patients with MFP experienced a decrease in whole-brain gray matter CBF-FCS coupling. In patients with MFP, a decrease in CBF/FCS was found in the bilateral superior temporal gyri, right parahippocampal gyrus, right hippocampus, caudate nucleus, right medial prefrontal cortex, and the periaqueductal gray matter (PAG), whereas an increase in CBF/FCS was found in the bilateral lingual gyri, posterior cingulate cortex, and bilateral inferior parietal lobules. In addition, the CBF/FCS of the PAG in patients with MFP was significantly negatively correlated with the pain visual analog scale score and pain duration. Alterations in neurovascular coupling in patients with MFP were observed only before treatment. Therefore, there is a lack of data on the alterations that occurred after treatment. This study demonstrated for the first time that impairment of neurovascular coupling in the brain may be a potential neuropathological mechanism of chronic MFP.

Anomalous neurovascular coupling in patients with generalized anxiety disorder evaluated by combining cerebral blood flow and functional connectivity strength

Coupling between neuronal activity and blood perfusion is termed neurovascular coupling, and it provides a new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in generalized anxiety disorder (GAD), whether anomalous neurovascular coupling would still be presented in such disease is hitherto unknown. In this study, the neuronal activity and blood supply were measured using the functional connectivity strength (FCS) and cerebral blood flow (CBF). The voxel-wise CBF–FCS correlations and CBF/FCS ratio were separately used to assess global and local neurovascular coupling in participants. Patients with GAD showed decreased voxel-wise CBF–FCS correlation, implicating global neurovascular decoupling. They also exhibited increased CBF/FCS ratio in the right superior parietal gyrus (SPG), and the enhanced CBF/FCS ratio in this region was negatively correlated with the self-esteem scores of GAD. The abnormal neurovascular coupling of GAD may indicate the disrupted balance between the intrinsic functional organization of the brain and corresponding blood perfusion of patients, and the abnormally increased local neurovascular coupling of the right SPG may be correlated with the abnormal self in GAD. These findings provide new information in understanding the brain dysfunction and abnormal cognition of GAD from the perspective of neurovascular coupling.

Retinal Neurovascular Coupling in Diabetes.

Neurovascular coupling, also termed functional hyperemia, is one of the physiological key mechanisms to adjust blood flow in a neural tissue in response to functional activity. In the retina, increased neural activity, such as that induced by visual stimulation, leads to the dilatation of retinal arterioles, which is accompanied by an immediate increase in retinal and optic nerve head blood flow. According to the current scientific view, functional hyperemia ensures the adequate supply of nutrients and metabolites in response to the increased metabolic demand of the neural tissue. Although the molecular mechanisms behind neurovascular coupling are not yet fully elucidated, there is compelling evidence that this regulation is impaired in a wide variety of neurodegenerative and vascular diseases. In particular, it has been shown that the breakdown of the functional hyperemic response is an early event in patients with diabetes. There is compelling evidence that alterations in neurovascular coupling precede visible signs of diabetic retinopathy. Based on these observations, it has been hypothesized that a breakdown of functional hyperemia may contribute to the retinal complications of diabetes such as diabetic retinopathy or macular edema. The present review summarizes the current evidence of impaired neurovascular coupling in patients with diabetes. In this context, the molecular mechanisms of functional hyperemia in health and disease will be covered. Finally, we will also discuss how neurovascular coupling may in future be used to monitor disease progression or risk stratification.

Acquired epileptiform opercular syndrome evaluated with real-time transcranial Doppler ultrasound-video-electroencephalogram before and after treatment: a case report

BackgroundAcquired epileptiform opercular syndrome (AEOS) with electrical status epilepticus during sleep (ESES) may be recurrent and intractable. The real-time transcranial Doppler ultrasound–sleep-deprived video electroencephalogram (TCD-SDvEEG) can be used to observe the relationships among hemodynamic, electrophysiological, and clinical factors in a patient during therapy. This study reported the case of a healthy 5-year-old boy with AEOS.Case presentationThe patient had initial seizures during sleep at the age of 1 year, with the left mouth pouting, left eye blinking and drooling for several seconds, and, sometimes, the left upper-limb flexion and head version to the left, lasting for 1–2 min. The combined antiepileptic drug regimens, including valproate, lamotrigine, and clonazepam, failed in the present case. Therefore, the add-on high-dose methylprednisolone therapy was provided. Also, the serial TCD-SDvEEG was used to monitor the dynamic changes before and after add-on steroid treatment. The results showed less than 15% variation in the range of blood flow fluctuation with spikes during non-rapid eye movement sleep after treatment. This was similar to the outcomes in healthy children and also accorded with the clinical improvements such as seizure control, drooling control, and language ability melioration. However, 95% of spike-wave index (SWI) was still maintained. The improvements in cerebral hemodynamics and clinical manifestations were faster and earlier than the SWI progression.ConclusionsThe real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3months after ictus (group B: day 90±35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p<0.001) with gradual improvement in group B (p<0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p<0.001) and reduced area under the curve (p<0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p<0.05). Venous NVC was significantly delayed after SAH compared to group C (A p<0.001; B p<0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.

Impact of abnormal cerebrovascular reactivity on BOLD fMRI: a preliminary investigation of moyamoya disease.

SummaryBlood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) studies of patients with cerebrovascular disease have largely ignored the confounds associated with abnormal cerebral blood flow, vascular reactivity and neurovascular coupling. We studied BOLD fMRI activation and cerebrovascular reactivity in moyamoya disease. To characterize the impact of remote vascular demands on BOLD fMRI measurements, we varied the vascular territories engaged by manipulating the experimental task performed by the participants. Vascular territories affected by disease were identified using BOLD cerebrovascular reactivity. Preliminary evidence from two patients pre‐ and postrevascularization surgery and four controls indicates that neurovascular coupling in affected brain regions can be modulated by the task‐related vascular demands in unaffected regions. In one patient studied, we observed that brain regions with improved cerebrovascular reactivity after surgery demonstrated normalized neurovascular coupling, that is the degree to which neurovascular coupling was modulated by task‐related vascular demands was decreased. We propose that variations in task‐dependent neurovascular coupling in patients with moyamoya disease are likely related to vascular steal. While preliminary, our findings are a proof of concept of the limitations of BOLD fMRI in cerebrovascular disease and suggest a role for assessment of cerebrovascular reactivity to improve interpretation of task‐related BOLD fMRI activation.

Neurovascular coupling in patients with relapsing-remitting multiple sclerosis

ObjectivesAlso to the inflammatory demyelinating lesions and degenerative process, altered cerebrovascular reactivity or neurovascular coupling (NVC) might be considered as playing another role in the pathogenesis of multiple sclerosis. The objective of this study is to assess the NVC of patients with relapsing-remitting multiple sclerosis (RRMS) during the acute exacerbation period. Patients and methodsFour hundred fifty-eight patients with RRMS and 160 healthy subjects were screened for this study during the last 14 years. We performed transtemporal transcranial Doppler recordings from the P2-segments of both posterior cerebral arteries simultaneously during simple or complex visual stimulation. The NVC was defined as a relative increase of the blood flow velocities as a percentage change of the baseline values during visual stimulation. ResultsThe NVC to simple visual stimulation was significantly higher in the patients on both sides (37.2±13.5% and 36.0±14.8%; right and left side, respectively) from those of the controls (30.9±9.9% and 30.0±8.8%; right and left side, respectively) (p<0.01). Similarly, the NVC to complex visual stimulation was significantly higher in the patients (43.3±14.1% and 41.7±13.5%; right and left side, respectively) from those of the controls (38.6±14.2% and 37.6±14.1%; right and left side, respectively) (p<0.05). ConclusionOur results suggest that patients with RRMS during exacerbation period have more reactive neurovascular units in the occipital cortex.

Cerebrovascular reactivity and neurovascular coupling in patients with obstructive sleep apnea

Aim: Obstructive sleep apnea syndrome (OSAS) has been implicated as an independent risk factor for stroke. There are data suggesting the presence of lower cerebrovascular reactivity (CVR) as determined by transcranial Doppler (TCD) in patients with OSAS. We concurrently investigated neurovascular coupling (NVC) with visual stimulation, and CVR using breath-holding (BH) test on TCD in patients with OSAS. Materials and methods: Data were collected in 49 patients with moderate to severe OSAS, and compared to 15 healthy subjects matched for age and risk factors. The CVR to hypercapnia was measured by BH test, and the NVC was performed with visual stimulation. Results: There were no significant differences in baseline characteristics of patients and controls, except for BMI, which was significantly higher in patients with OSAS (p = 0.036). OSAS patients showed significantly lower reactivity during BH in comparison to controls (36.9% ± 14.0% vs. 46.6% ± 20.1%; p = 0.019). The reactivity time was also significantly shorter in the OSAS group (8.0 ± 4.2 s) when compared to controls (10.1 ± 4.3 s; p = 0.015). The visual stimulation produced similar reactivity in patients (27.7% ± 9.4%) and controls (29.1 ± 13.9; p > 0.05). Conclusions: Our data demonstrate a diminished vasodilator response capacity only to a strong stimulator such as hypercapnia in OSAS patients. However, the NVC, as shown by the TCD, is quite normal, suggesting that a weak or mild stimulation produces a proper reactivity among OSAS patients.

Real-time TCD-vEEG monitoring for neurovascular coupling in epilepsy

PurposeRecently, a novel multi-model monitor has been available, which integrates real-time signals of transcranial Doppler (TCD) and video-EEG (vEEG) into one workstation. We sought to test the feasibility of this device in detecting neurovascular coupling in patients with epilepsy. MethodCerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and vEEG during seizure episodes were recorded simultaneously in 12 patients (age 17–58 years) with partial epilepsies. The correlations between vEEG and CBFV findings were analyzed. ResultsEleven seizure episodes were detected in 5 patients. Of them, bilateral CBFV increase with interhemispheric asymmetry was observed in 4 seizure episodes of 3 patients. EEG abnormalities preceded CBFV increase by 1–3s at the onset of a seizure. In a patient with bilateral middle cerebral artery stenosis, no apparent CBFV changes were detected during 2 of 3 seizure episodes. Another patient with previous frontal hemorrhage displayed CBFV increase without interhemispheric asymmetry during 4 seizure episodes. ConclusionIt is feasible to evaluate neurovascular coupling with good temporal correlation in patients with frequent seizure episodes by real-time TCD-vEEG monitoring.

Altered somatosensory neurovascular coupling in patients with becker muscular dystrophy

Background: In patients suffering from Becker muscular dystrophy (BMD) variable degrees of cognitive impairment have been reported in addition to the well-known muscular and cardiac symptoms. BMD is caused by mutations in the dystrophin gene, changing the cellular dystrophin complex and subsequent muscular blood flow. Few studies have addressed the mechanisms of cognitive impairment. Lack of dystrophin, however, causes secondary loss of vasoactive molecules such as nitric oxide, which is as an important player in brain vascular control.

Retinal neurovascular coupling in patients with glaucoma and ocular hypertension and its association with the level of glaucomatous damage

To analyze neurovascular coupling in the retina of untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. Maximal vessel dilation in response to flicker light was analyzed with Retinal Vessel Analyzer (RVA) in temporal superior/inferior arterioles and veins in 51 POAG patients, 46 OHT and 59 control subjects. RVA parameters were compared between groups, between contralateral POAG eyes, and correlated to intraocular pressure, visual field mean defect and retinal nerve fiber layer thickness. POAG eyes demonstrated generally smaller response of all vessels to flicker light than the other two groups (ANOVA p=0.026; mean arterial flicker response in percent of baseline, averaged superior and inferior was 3.48 ± 2.22 % for controls , 2.35 ± 2.06 % for POAG patients , and 2.97 ± 2.35 % for OHT patients; corresponding values for venules were 3.88 ± 1.98 %, 2.89 ± 1.72 %, 3.45 ± 2.77 %). There was no difference in flicker response between the eye with more and less advanced damage in each patient of the POAG group (ANOVA p=0.79). Correlation of flicker response to intraocular pressure (IOP) was borderline at best, correlations to the level of glaucomatous damage were not significant. Correlation of flicker response of superior and inferior vessels of the same eye was significant for the arteries (Pearson r=0.23, p=0.004), as well as venules (r=0.52, p<0.001). General vessel response to flicker light was decreased in POAG patients, compared to normal controls and OHT patients. In contrast to significant correlation between the two contralateral eyes of the flicker response itself, only its borderline correlation to IOP was seen. There was no correlation to the level of damage, altogether indicating a systemic dysregulation phenomenon. GRANTS: Swiss National Foundation Grant 3200B0-113685, Velux Stiftung Grant, Freie Akademische Gesellschaft (FAG) Grant, Pfizer Inc. Grant CLINICAL TRIAL REGISTRATION REFERENCE NUMBER: ClinicalTrials.gov NCT00430209.

Early neurovascular uncoupling in the brain during community acquired pneumonia

IntroductionSepsis leads to microcirculatory dysfunction and therefore a disturbed neurovascular coupling in the brain. To investigate if the dysfunction is also present in less severe inflammatory diseases we studied the neurovascular coupling in patients suffering from community acquired pneumonia.MethodsPatients were investigated in the acute phase of pneumonia and after recovery. The neurovascular coupling was investigated with a simultaneous electroencephalogram (EEG)-Doppler technique applying a visual stimulation paradigm. Resting EEG frequencies, visual evoked potentials as well as resting and stimulated hemodynamic responses were obtained. Disease severity was characterized by laboratory and cognitive parameters as well as related scoring systems. Data were compared to a control group.ResultsWhereas visually evoked potentials (VEP) remained stable a significant slowing and therefore uncoupling of the hemodynamic responses were found in the acute phase of pneumonia (Rate time: control group: 3.6 ± 2.5 vs. acute pneumonia: 1.6 ± 2.4 s; P < 0.0005). In the initial investigation, patients who deteriorated showed a decreased hemodynamic response as compared with those who recovered (gain: recovered: 15% ± 4% vs. deteriorated: 9% ± 3%, P < 0.05; control: 14% ± 5%). After recovery the coupling normalized.ConclusionsOur study underlines the role of an early microcirculatory dysfunction in inflammatory syndromes that become evident in pre-septic conditions with a gradual decline according to disease severity.

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity.