Blood pressure variability at rest and during pressor challenges in patients with acute ischemic stroke.

INTRODUCTION: Patients with acute ischemic stroke (AIS) have elevated blood pressure (BP) variability (BPV) and reduced baroreflex sensitivity (BRS) at rest for several days after initial stroke symptoms. We aimed to assess BPV and BRS in AIS patients during pressor challenge maneuvers in the acute and subacute phases of stroke. Pressor challenge maneuvers simulate day-to-day activities and can predict the quality of life. METHODS: Continuous beat-to-beat BP and ECG in 15 AIS patients (mean age 69 ±â€…7.5 years) and 15 healthy controls (57 ±â€…16 years) were recorded at rest and during a 5-min rapid head positioning (RHP) paradigm. Patients were assessed within 24 h (acute phase) and 7 days (subacute phase) of stroke onset. Low frequency (LF) SBP power (measure of BPV), LF-α, and combined α-index (measure of BRS) were calculated from the recordings. RESULTS: In the acute phase, at rest, LF-SBP power was higher ( P  = 0.024) and α-index was lower ( P  = 0.006) in AIS patients than in healthy controls. There was no change in LF-SBP during RHP in the patients but in healthy controls, it increased significantly ( P  = 0.018). In the subacute phase, at rest, the alpha-index increased ( P  = 0.037) and LF-SBP decreased ( P  = 0.029) significantly in the AIS patients, however, there was still no rise in the LF-SBP power during RHP ( P  = 0.240). CONCLUSION: AIS patients have a high resting BPV. High resting BPV may be responsible for blunted BPV responses during pressor challenge maneuvers such as RHP, suggesting ongoing autonomic dysfunction and compromised quality of life.

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood-brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.

The role of the autonomic nervous system in cerebral blood flow regulation in stroke: A review.

Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients.

COVID-19 disease in hospitalized young adults in India and China: Evaluation of risk factors predicting progression across two major ethnic groups.

Data pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes.

Cardiovascular fingolimod effects on rapid baroreceptor unloading are counterbalanced by baroreflex resetting.

BACKGROUND AND PURPOSE: Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. PATIENTS AND METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours after fingolimod initiation. We recorded heart rate (HR) as RR intervals (RRI), systolic and diastolic BP (BPsys, BPdia) during VM phase 1, VM phase 2 early, VM phase 2 late, and VM phase 4. Using linear regression analysis between decreasing BPsys and RRI values during VM phase 2 early, we determined baroreflex gain (BRG) reflecting vagal withdrawal and sympathetic activation upon baroreceptor unloading. To assess cardiovagal activation upon baroreceptor loading, we calculated Valsalva ratios (VR) between maximal and minimal RRIs after strain release. Analysis of variance or Friedman tests with post hoc analysis compared corresponding parameters at the eight time points (significance: p < 0.05). RESULTS: RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation. CONCLUSIONS: VR-decreases 3-6 hours after fingolimod initiation are physiologic results of fingolimod-associated attenuations of BP and HR increases at the end of strain and do not suggest impaired cardiovagal activation upon baroreceptor loading. Stable and at the time of HR nadir significantly increased BRGs indicate improved responses to baroreceptor unloading. Thus, cardiovascular fingolimod effects do not impair autonomic responses to sudden baroreceptor loading or unloading but seem to be mitigated by baroreflex resetting.

Autonomic dysfunction in the neurological intensive care unit.

Autonomic dysfunction is common in neuro-critical care patients and may compromise the function of various organs. Among the many diseases causing or being associated with autonomic dysfunction are traumatic brain injury, cerebrovascular diseases, epilepsy, Guillain-Barré syndrome (GBS), alcohol withdrawal syndrome, botulism and tetanus, among many others. Autonomic dysfunction may afflict various organs and may involve hyper- or hypo-activity of the sympathetic or parasympathetic system. In this short overview, we address only a small number of neuro-intensive care diseases with autonomic dysfunction. In GBS, autonomic dysfunction is frequent and may account for increased mortality rates; rapid changes between sympathetic and parasympathetic hypo- or hyper-activity may cause life-threatening cardiovascular complications. Paroxysmal sympathetic hyperactivity occurs after brain injury, hypoxia and cerebrovascular and other events, causes paroxysmal tachycardia, hypertension, tachypnoea and hyperthermia and is associated with a poorer prognosis and prolonged intensive care treatment. Other, at times life-threatening autonomic complications with exaggerated sympathetic activity and compromised baroreflex sensitivity arise during the alcohol withdrawal syndrome triggered by abrupt cessation of alcohol consumption. Botulism and tetanus are examples of life-threatening autonomic dysfunction caused by bacterial neurotoxins. Common neurological diseases, such as epilepsy, stroke or subarachnoid haemorrhage, are also associated with autonomic dysfunction that can on occasion cause critical deterioration of disease severity and prognosis.

Sexual Dysfunction Seems to Trigger Depression in Female Multiple Sclerosis Patients.

BACKGROUND: In women with multiple sclerosis (MS), depression and sexual dysfunction (SD) are common. Whether SD promotes depression or vice versa remains unclear despite therapeutic relevance. Therefore, we aimed to assess whether SD more likely triggers depression or vice versa. METHODS: In 83 female MS patients and 21 age-matched healthy women, we assessed depression, using the Beck Depression Inventory-V (BDI-V), and SD using the Female Sexual Function Index (FSFI). We diagnosed depression with BDI-V-scores >35 and SD with FSFI scores < 26.55. We divided patients into groups with and without SD, with and without depression. Between groups, we compared prevalence of SD and depression (Fisher's-exact-test), age, MS-duration, MS-severity, BDI-V-, and FSFI scores (Mann-Whitney U-test; significance: p < 0.05). RESULTS: A total of 37/83 MS patients and 1/21 controls had SD; 28/83 patients and 3/21 controls had depression; 51.4% patients with SD but only 19.6% without SD had depression (p = 0.003). SD was present in 67.9% depressed and 32.7% non-depressed patients. BDI-V-scores were higher in patients with SD than in patients without SD. FSFI scores were lower in depressed than non-depressed patients. CONCLUSION: In conclusion, SD was more common than depression. SD afflicted 67.9% depressed MS patients and was also more common in non-depressed MS patients than controls. SD may occur independently from depression while increased depressiveness seems linked to coexistent SD.

Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury.

OBJECTIVE: After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. METHODS: In 51 post-moderate-severe-TBI patients (32.7 ±â€¯10.5 years old, 43.1 ±â€¯33.4 months post-injury), and 30 controls (29.1 ±â€¯9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). RESULTS: At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. CONCLUSIONS: In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. SIGNIFICANCE: Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI.

Fingolimod initiation in multiple sclerosis patients is associated with potential beneficial cardiovascular autonomic effects.

BACKGROUND: Fingolimod slows heart rate (HR) due to vagomimetic effects and might cause additional cardiovascular autonomic changes. While the time course of HR changes is well described, the extent and course of cardiovascular autonomic changes upon fingolimod initiation has not yet been evaluated. This study, therefore, intended to assess cardiovascular autonomic changes during the first 6 h after fingolimod initiation. METHODS: In 21 patients with relapsing-remitting multiple sclerosis (RRMS), we recorded respiration (RESP), electrocardiographic RR interval (RRI), systolic and diastolic blood pressure (BPsys, BPdia) at rest, before and 0.5, 1, 2, 3, 4, 5, and 6 h after fingolimod initiation. We calculated parameters of total autonomic modulation [RRI standard deviation (RRI-SD), RRI coefficient of variation (RRI-CV), RRI-total powers], mainly sympathetic cardiac modulation [RRI low frequency (LF) powers], sympathetic BP modulation (BPsys-LF powers), parasympathetic modulation [square root of the mean squared difference of successive RRIs (RMSSD), RRI high frequency (HF) powers], sympatho-vagal cardiac balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). We compared parameters between the eight measurements [analysis of variance (ANOVA) or Friedman test with post-hoc analysis; significance: p < 0.05]. RESULTS: After fingolimod initiation, RESP, BPsys, and BPsys-LF powers remained unchanged while RRIs, RRI-CV, RRI-SD, RRI-total powers, RRI-LF powers, RMSSD, RRI-HF powers, and BRS increased after 1 h and rose to peak values occurring after 5, 1, 2, 2, 1, 4, 4, and 4 h, respectively. After 3 h, BPdia had decreased significantly and was lowest after 5 h. RRI-LF/HF ratios decreased to a nadir after 4 h. CONCLUSIONS: The increases in parasympathetic and overall cardiac autonomic modulation and in BRS seen with fingolimod initiation are theoretically beneficial for the MS patient's cardiovascular system. However, long-term studies must show whether these effects persist or are attenuated (e.g. due to S1P1 receptor down-regulation upon continued fingolimod therapy).

Cardiovagal Baroreflex Sensitivity in Parkinson's Disease and Multiple-System Atrophy.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) and multiple-system atrophy of the parkinsonian type (MSA-P) are progressive neurodegenerative disorders that in addition to dysfunction of the motor system also present with features of dysautonomia, frequently manifesting as orthostatic hypotension (OH). The pathophysiology of OH has been proposed to differ between these two disorders. This study investigated the spontaneous and cardiovagal baroreflex sensitivity (BRS) in Parkinson's disease patients with orthostatic hypotension (PD(OH)) and multiple system atrophy of Parkinsonian type with orthostatic hypotension in an attempt to differentiate the two disorders. METHODS: Two methods were used for determining the BRS: a spontaneous method (spontaneous BRS) and the reflexive baroreflex gain (cardiovagal BRS) from phases II and IV of the Valsalva maneuver (VM) in PD(OH) and MSA-P(OH). RESULTS: The spontaneous BRS (5.04±0.66 ms/mm Hg vs. 4.78±0.64 ms/mm Hg, p=0.54) and the cardiovagal BRS from phase II of the VM (0.96±0.75 ms/mm Hg vs. 1.34±1.51 ms/mm Hg, p=0.76) did not differ between PD(OH) and MSA-P(OH), but the cardiovagal BRS from phase IV of the VM (0.03±0.07 ms/mm Hg vs. 2.86±2.39 ms/mm Hg, p=0.004) was significantly lower in PD(OH). CONCLUSIONS: The cardiovagal BRS from phase IV of the VM has potential for differentiating PD(OH) and MSA-P(OH), indicating a difference in the pathophysiological mechanisms underlying the autonomic dysfunction in the two disorders.

Cardiovascular responses during cold pressor test are different in Parkinson disease and multiple system atrophy with parkinsonism.

OBJECTIVE: Orthostatic hypotension (OH) is common in Parkinson disease (PD) and multiple system atrophy of parkinsonian type (MSA-P), but the pathophysiology of OH is different in the two. We hypothesised that the baroreflex-independent sympathetic reactivity may also be different in them. To evaluate this we assessed the sympathetic vascular reactivity and the heart rate response to the standard cold pressor test (CPT) in these patients. METHODS: The study was conducted in ten patients with PD with OH, 5 PD without OH, 13 MSA-P with OH, and 7 MSA-P without OH. Lead II ECG and finger PPG (photoplethysmography) were simultaneously acquired during a baseline period of 1 min followed by a 10 °C cold exposure (1 min) of the contralateral hand (CPT). The vascular response was then evaluated by computing the pulse transit time (PTT). RESULTS: The percentage decrease in PTT during the CPT was significantly higher in patients with PD as compared to MSA-P, irrespective of the presence or absence of OH (-2.74 ± 0.96 vs -0.05 ± 0.75 %, p = 0.03; PD vs MSA-P with OH and -3.04 ± 0.85 vs 0.48 ± 1.13 %, p = 0.04; PD vs MSA-P without OH). The rise in heart rate during CPT was similar in patients with PD and MSA-P with or without OH (4.95 ± 1.6 vs 5.99 ± 1.04, p = 0.28; PD vs MSA-P with OH and 5.62 ± 1.31 vs 13.15 ± 2.89, p = 0.06; PD vs MSA-P without OH). INTERPRETATION: Vasoconstrictor response to CPT is compromised in MSA-P as compared to PD, but the baroreflex-independent heart rate response is similar in the two.