scholarly journals Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy

2021 ◽  
Vol 11 (4) ◽  
pp. 313
Author(s):  
Shu-Fang Chen ◽  
Hsiu-Yung Pan ◽  
Chi-Ren Huang ◽  
Jyun-Bin Huang ◽  
Teng-Yeow Tan ◽  
...  

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

2014 ◽  
Vol 117 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Pedro M. Castro ◽  
Rosa Santos ◽  
João Freitas ◽  
Ronney B. Panerai ◽  
Elsa Azevedo

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI( t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP and CVRi increased similarly in both groups during strain. ARI( t) showed a biphasic variation in controls with initial increase followed by a decrease during phase II but in FAP this response was blunted (5.4 ± 3.0 and 2.0 ± 2.9; P = 0.033). Our data suggest that dynamic cerebral autoregulatory response is a time-varying phenomena during VM and that it is disturbed by autonomic dysfunction. This study also emphasizes the fact that RAP + CrCP model allowed additional insights into understanding of cerebral hemodynamics, showing a higher vasodilatory response expressed by RAP in AF and an equal CrCP response in both groups during the increased intracranial and intrathoracic pressure, while classical CVRi paradoxically suggests a cerebral vasoconstriction.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mika Jönsson ◽  
Björn Gerdle ◽  
Bijar Ghafouri ◽  
Emmanuel Bäckryd

Abstract Background Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. Methods The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. Results We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). Conclusions Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.


2009 ◽  
Vol 107 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
Andrew W. Subudhi ◽  
Ronney B. Panerai ◽  
Robert C. Roach

We investigated the effect of acute hypoxia (AH) on dynamic cerebral autoregulation (CA) using two independent assessment techniques to clarify previous, conflicting reports. Twelve healthy volunteers (6 men, 6 women) performed six classic leg cuff tests, three breathing normoxic (FiO2 = 0.21) and three breathing hypoxic (FiO2 = 0.12) gas, using a single blinded, Latin squares design with 5-min washout between trials. Continuous measurements of middle cerebral artery blood flow velocity (CBFv; DWL MultiDop X2) and radial artery blood pressure (ABP; Colin 7000) were recorded in the supine position during a single experimental session. Autoregulation index (ARI) scores were calculated using the model of Tiecks et al. (Tiecks FP, Lam AM, Aaslid R, Newell DW. Stroke 26: 1014–1019, 1995) from ABP and CBFv changes following rapid cuff deflation (cuff ARI) and from ABP to CBFv transfer function, impulse, and step responses (TFA ARI) obtained during a 4-min period prior to cuff inflation. A new measure of %CBFv recovery 4 s after peak impulse was also derived from TFA. AH reduced cuff ARI (5.65 ± 0.70 to 5.01 ± 0.96, P = 0.04), TFA ARI (4.37 ± 0.76 to 3.73 ± 0.71, P = 0.04), and %Recovery (62.2 ± 10.9% to 50.8 ± 9.9%, P = 0.03). Slight differences between TFA and cuff ARI values may be attributed to heightened sympathetic activity during cuff tests as well as differential sensitivity to low- and high-frequency components of CA. Together, results provide consistent evidence that CA is impaired with AH. In addition, these findings demonstrate the potential utility of TFA ARI and %Recovery scores for future CA investigations.


2017 ◽  
Vol 107 (4) ◽  
pp. 653-657 ◽  
Author(s):  
H Tomoum ◽  
N Habeeb ◽  
I Elagouza ◽  
H Mobarez

2020 ◽  
Author(s):  
Xialin Luo ◽  
Jingjing Liu ◽  
Huaizhi Wang ◽  
Haitao Lu

AbstractPurposeTo improve clinical diagnosis and enhance therapeutic outcome, we figure out to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can easily, sensitively and efficiently diagnose the onsite progression, and metastasis of the disease.Experimental DesignWe employed the newly developed precision-targeted metabolomics method to validate that many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer from healthy controls. To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance.ResultsWe eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); Moreover, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages.ConclusionsTaken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficiently therapeutic interventions, which could largely improve the five-year survival rate of PC patients.


2020 ◽  
Author(s):  
Rizwan Qaisar ◽  
Mughal Qayyum ◽  
Tahir Muhammad

Abstract Background The potential contribution of chronic dysregulation of sarcoplasmic reticulum (SR) protein homeostasis (a condition called SR stress) to skeletal muscle loss is poorly understood. We investigated the degree of activation of SR stress in locomotor muscles of patients with chronic obstructive pulmonary disease (COPD), a respiratory disease with systemic manifestations. Methods We analyzed the markers of SR stress and associated pathologies in vastus lateralis muscles of 60-65 years old male healthy controls and patients with mild (COPD stages 1 & 2) and advanced (COPD stages 3 & 4) COPD (N = 6-8 / group). Results Skeletal muscle proteins expressions of GRP94, BiP, CHOP and ATF were significantly elevated in advanced COPD (≈53%, ≈3.6 fold, ≈3.5 fold and ≈3.2 fold, respectively) compared with healthy controls. The expression of downstream markers of SR stress including apoptosis, inflammation and autophagy was increased, while the maximal activity of SR Ca2+ ATPase (SERCA) enzyme was significantly reduced in advanced COPD (≈41%) than healthy controls. Single muscle fiber diameter and cytoplasmic domain per myonucleus were significantly smaller (≈14% and 13%, respectively) in patients with advanced COPD than healthy controls. These changes in SR dysfunction were accompanied by substantially elevated levels of global oxidative stress including lipid peroxidation and mitochondrial ROS production. Conclusion Taken together, our data suggests that the muscle weakness in advanced COPD is in part driven by elevated SR stress and its pathological consequences. The data provided can lead to potential therapeutic interventions of SR dysfunction for muscle detriment in COPD.


Stroke ◽  
1996 ◽  
Vol 27 (7) ◽  
pp. 1177-1182 ◽  
Author(s):  
Frank P. Tiecks ◽  
Colleen Douville ◽  
Sheila Byrd ◽  
Arthur M. Lam ◽  
David W. Newell

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A Ashour ◽  
A M A Nassef ◽  
E M Awad ◽  
A M Hazzou ◽  
M A Nada ◽  
...  

Abstract Background Epilepsy is a serious common neurological disorder that can affect any age. Cognitive functions are highly prevalent in patients with epilepsy and is more likely to occur in patients with idiopathic generalized epilepsy (IGE). Associations were found between cognitive functions and brain volume loss in patients with epilepsy. Objective This work was carried out to assess the volumetric changes in brain of epileptic patients to use it as a biomarker for cognitive dysfunction in adult and adolescent patients with epilepsy. Patients and Methods A case control study was conducted to include 61 patients, 20 of which diagnosed with idiopathic generalized epilepsy (IGE), 21 with temporal lobe epilepsy (TLE) and 20 with frontal lobe epilepsy (FLE) who were selected from the epilepsy outpatient clinic in Ain Shams university hospitals along with 23 age and sex matched healthy controls. Both cases and control groups were subjected to Magnetic resonance imaging MRI brain volumetry and detailed cognitive testing. An informed consent was taken from each adult patient, guardian of adolescent patient and healthy control. Results Statistically significant difference in comprehension subcategory of the Wechsler adult intelligence scale (WAIS) between patients with IGE and healthy controls denoting poorer social judgment in the IGE group. The IGE group also showed poorer performance in digit symbol subcategory of the same test denoting worse psychomotor speed and sustained attention. Also, significant difference in similarities subcategory was found between TLE group and control group denoting poorer abstract thinking among the TLE group. The IGE and TLE groups also showed lower attention and concentration than control group in the mental control subcategory of the Wechsler memory scale (WMS) yet failed to show superiority over each other. No statistically significant difference was found on comparing the whole brain volume between cases and control groups. A statistically significant direct relationship was found between the arithmetic subcategory of WAIS and the whole brain volume of the patients among the patients of the FLE group. Conclusion Patients with IGE had worse psychomotor speed, sustained attention and concentration than healthy controls in addition to poorer social judgment. Also, patients with TLE showed lower attention and concentration together with poorer abstract thinking despite normal IQ. The study also concluded that increased whole brain volume in patients with frontal lobe epilepsy is associated with better mathematical problem solving.


2018 ◽  
Vol 39 (11) ◽  
pp. 2277-2285 ◽  
Author(s):  
Angela SM Salinet ◽  
Nathália CC Silva ◽  
Juliana Caldas ◽  
Daniel S de Azevedo ◽  
Marcelo de-Lima-Oliveira ◽  
...  

We aimed to assess cerebral autoregulation (CA) and neurovascular coupling (NVC) in stroke patients of differing severity comparing responses to healthy controls and explore the association between CA and NVC with functional outcome. Patients admitted with middle cerebral artery (MCA) stroke and healthy controls were recruited. Stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS) scores: ≤4 mild, 5–15 moderate and ≥16 severe. Transcranial Doppler ultrasound and Finometer recorded MCA cerebral blood flow velocity (CBFv) and blood pressure, respectively, over 5 min baseline and 1 min passive movement of the elbow to calculate the autoregulation index (ARI) and CBFv amplitude responses to movement. All participants were followed up for three months. A total of 87 participants enrolled in the study, including 15 mild, 27 moderate and 13 severe stroke patients, and 32 control subjects. ARI was lower in the affected hemisphere (AH) of moderate and severe stroke groups. Decreased NVC was seen bilaterally in all stroke groups. CA and NVC correlated with stroke severity and functional outcome. CBFv regulation is significantly impaired in acute stroke, and further compromised with increasing stroke severity. Preserved CA and NVC in the acute period were associated with improved three-month functional outcome.


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