Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

PubMed

Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

2016-06-01

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. © The American Society of Tropical Medicine and Hygiene.

Cardiac autonomic function in children with type 1 diabetes.

PubMed

Metwalley, Kotb Abbass; Hamed, Sherifa Ahmed; Farghaly, Hekma Saad

2018-06-01

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

Laughter is not always funny: breath-holding spells in familial dysautonomia.

PubMed

Maayan, Channa; Katz, Eliot; Begin, Michal; Yuvchev, Ivelin; Kharasch, Virginia S

2015-02-01

Familial dysautonomia (FD) is a genetic disease characterized by primary autonomic dysfunction including parasympathetic hypersensitivity. Breath-holding spells (BHS) are believed to be caused by autonomic dysregulation mediated via the vagus nerve and increased in patients with a family history of BHS. Details and understanding of its pathophysiology are lacking. In this retrospective study of patients with FD, the incidence of BHS was higher at 53.3%, compared with previous studies in normal children. Laughter as a precipitating factor for BHS has not been previously reported in FD and occurred in 10% of patients in this study. Lower lung volumes, chronic lung disease, chronic CO2 retention, and inadequate autonomic compensation occur in those with FD leading to a higher incidence and severity of BHS when crying or laughing. Thus, FD may be a good model for understanding manifestations of the autonomic nervous system dysfunction and contribute to our knowledge of BHS mechanisms. © The Author(s) 2014.

Motor Neuron Rescue in Spinal Muscular Atrophy Mice Demonstrates That Sensory-Motor Defects Are a Consequence, Not a Cause, of Motor Neuron Dysfunction

PubMed Central

Gogliotti, Rocky G.; Quinlan, Katharina A.; Barlow, Courtenay B.; Heier, Christopher R.; Heckman, C. J.

2012-01-01

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction. PMID:22423102

Altered Behavioral and Autonomic Pain Responses in Alzheimer’s Disease Are Associated with Dysfunctional Affective, Self-Reflective and Salience Network Resting-State Connectivity

PubMed Central

Beach, Paul A.; Huck, Jonathan T.; Zhu, David C.; Bozoki, Andrea C.

2017-01-01

While pain behaviors are increased in Alzheimer’s disease (AD) patients compared to healthy seniors (HS) across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores) and autonomic (heart rate, HR) pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score) were increased in patients vs. controls. Autonomic measures (HR change intercept and mean HR change) were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN) and between the TLN and ventromedial prefrontal cortex (vmPFC); between default mode network (DMN) subcomponents; between the DMN and ventral salience network (vSN). Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN—specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation. PMID:28959201

Post-neonatal Tetanus in a PICU of a Developing Economy: Intensive Care Needs, Outcome and Predictors of Mortality.

PubMed

Angurana, Suresh Kumar; Jayashree, Muralidharan; Bansal, Arun; Singhi, Sunit; Nallasamy, Karthi

2018-02-01

To evaluate pediatric intensive care unit (PICU) needs, outcome and predictors of mortality in post-neonatal tetanus. Review of 30 consecutive post-neonatal tetanus cases aged 1 months to 12 years admitted to a PICU in north India over a period of 10 years (January 2006 to December 2015). Chronic suppurative otitis media was the commonest portal of entry. All received tetanus toxoid, human tetanus immunoglobulin (HTIG) and appropriate antibiotics; 7 (23.3%) received intrathecal HTIG. Common complications were respiratory failure, rhabdomyolysis, autonomic dysfunction, acute kidney injury and healthcare-associated infections. PICU needs were as follows: ventilation; benzodiazepine, morphine and magnesium sulfate infusion; neuromuscular blockers, inotropes, tracheostomy and renal replacement therapy. Mortality rate was 40%; severity Grade IIIb, autonomic dysfunction, use of vasoactive drugs and those who did not receive intrathecal HTIG were significantly associated with mortality. Post-neonatal tetanus is associated with high mortality, and PICU needs include management of spasms, autonomic dysfunction and complications and cardiorespiratory support. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies.

PubMed

Molenaar, Joery P; Wilbers, Joyce; Aerts, Marjolein B; Leijten, Quinten H; van Dijk, Jan G; Esselink, Rianne A; Bloem, Bastiaan R

2016-01-01

We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA.

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following SCI. Each type of cardiac disturbance requires specific treatment. PMID:20108532

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Gagnon, Jean-Francois; Vendette, Melanie; Charland, Katia; Montplaisir, Jacques

2008-09-15

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = -25.7 +/- 13.0 mmHg vs. -4.9 +/-14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease-specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked. (c) 2007 Movement Disorder Society.

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People.

PubMed

Oosterwijck, Jessica Van; Marusic, Uros; De Wandele, Inge; Paul, Lorna; Meeus, Mira; Moorkens, Greta; Lambrecht, Luc; Danneels, Lieven; Nijs, Jo

2017-03-01

Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity. A controlled experimental study. The study was conducted at the Human Physiology lab of a University. Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis. Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability. Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations. Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.Key words: Aerobic exercise, aerobic power index, autonomic nervous system, exercise-induced analgesia, exercise-induced hypoalgesia, fibromyalgia, heart rate variability, stress-induced analgesia, pain.

Takotsubo cardiomyopathy associated with Miller-Fisher syndrome.

PubMed

Gill, Dalvir; Liu, Kan

2017-07-01

51-year-old female who presented with progressive paresthesia, numbness of the lower extremities, double vision, and trouble walking. Physical exam was remarkable for areflexia, and ptosis. Her initial EKG showed nonspecific ST segment changes and her Troponin T was elevated to 0.41ng/mL which peaked at 0.66ng/mL. Echocardiogram showed a depressed left ventricular ejection fraction to 35% with severely hypokinetic anterior wall and left ventricular apex was severely hypokinetic. EMG nerve conduction study showed severely decreased conduction velocity and prolonged distal latency in all nerves consistent with demyelinating disease. She was treated with 5days of intravenous immunoglobulin therapy to which she showed significant improvement in strength in her lower extremities. Echocardiogram repeated 4days later showing an improved left ventricular ejection fraction of 55% and no left ventricular wall motion abnormalities. Takotsubo cardiomyopathy is a rare complication of Miller-Fisher syndrome and literature review did not reveal any cases. Miller-Fisher syndrome is an autoimmune process that affects the peripheral nervous system causing autonomic dysfunction which may involve the heart. Due to significant autonomic dysfunction in Miller-Fisher syndrome, it could lead to arrhythmias, blood pressure changes, acute coronary syndrome and myocarditis, Takotsubo cardiomyopathy can be difficult to distinguish. The treatment of Takotsubo cardiomyopathy is supportive with beta-blockers and angiotensin-converting enzyme inhibitors are recommended until left ventricle ejection fraction improvement. Takotsubo cardiomyopathy is a rare complication during the acute phase of Miller-Fisher syndrome and must be distinguished from autonomic dysfunction as both diagnoses have different approaches to treatment. Published by Elsevier Inc.

Anesthetic considerations for rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction (ROHHAD) syndrome in children.

PubMed

Chandrakantan, Arvind; Poulton, Thomas J

2013-01-01

Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction is an increasingly common diagnosis in patients who are being seen at tertiary care children's hospitals. We present two cases of anesthetics from the authors' own experience in addition to a comprehensive review of the disorder and anesthetic implications. © 2012 Blackwell Publishing Ltd.

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.

PubMed

Palma, Jose-Alberto; Kaufmann, Horacio

2018-03-01

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

"A" motor neuron disease.

PubMed

Vishnu, Venugopalan Y; Modi, Manish; Prabhakar, Sudesh; Bhansali, Anil; Goyal, Manoj Kumar

2014-01-15

Allgrove syndrome is a rare autosomal recessive disorder characterised by achalasia, alacrima, adrenal insufficiency, autonomic dysfunction and amyotrophy. The syndrome has been described in childhood and adult presentation, as in our case, is very rare. There is a considerable delay in diagnosis due to lack of awareness about the syndrome. We report a single case of a 36 year old man who was initially diagnosed and treated for achalasia cardia in our institute 14 years before. After 8 years he presented again with weakness and wasting predominantly distally. He had tongue fasciculations, brisk reflexes and extensor plantar. After supportive electrophysiological studies he was diagnosed as Amyotrophic lateral sclerosis. After 5 years he presented with generalised fatigue without any significant worsening of his neurological status. On reevaluation he had alacrimia, autonomic dysfunction and mild ACTH resistance. Allgrove syndrome may be an underdiagnosed cause of multisystem neurological disease due to the heterogeneous clinical presentation as well as for ignorance of clinician about the syndrome. Based on our case, we also believe that there does exist a subgroup of patients who follow a less severe and chronic course. Recognition of syndrome allows for treatment of autonomic dysfunction, adrenal insufficiency and dysphagia. © 2013.

The nature of the autonomic dysfunction in multiple system atrophy

NASA Technical Reports Server (NTRS)

Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

2002-01-01

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

Autonomic dysfunction in pediatric patients with headache: migraine versus tension-type headache.

PubMed

Rabner, Jonathan; Caruso, Alessandra; Zurakowski, David; Lazdowsky, Lori; LeBel, Alyssa

2016-12-01

To examine symptoms indicating central nervous system (CNS) autonomic dysfunction in pediatric patients with migraine and tension-type headache. A retrospective chart review assessed six symptoms (i.e. constipation, insomnia, dizziness, blurry vision, abnormal blood pressure, and cold and clammy palms and soles) indicating central nervous system (CNS) autonomic dysfunction in 231 patients, ages 5-18 years, diagnosed with migraine, tension-type headache (TTH), or Idiopathic Scoliosis (IS). Higher frequencies of "insomnia," "dizziness," and "cold and clammy palms and soles" were found for both migraine and TTH patients compared to the IS control group (P < 0.001). Frequencies of all six symptoms were greater in TTH than migraine patients with "cold and clammy palms and soles" reaching significance (P < 0.001). The need for prospective research investigating autonomic dysfunction in pediatric headache patients is discussed.

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

PubMed

Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

2017-03-20

Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.

PubMed

Baker, Jacquie; Racosta, Juan M; Balint, Brittany; Kimpinski, Kurt

2018-03-01

The clinical significance of heart rate variability in the context of autonomic dysfunction continues to be a matter of debate. A consensus is lacking on the best heart rate variability measures for clinical purposes. Therefore, the purpose of this study was to investigate the utility of heart rate variability parameters in healthy versus autonomic dysfunction. Healthy young (n = 134), healthy older (n = 32), and patients with mild (postural tachycardia syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34) autonomic dysfunction were included. Time and frequency parameters during baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB) were compared. Cardiovagal time parameters were significantly reduced during HUT in healthy young and postural tachycardia syndrome (P < 0.001). Healthy young had significantly higher time parameters during baseline, HUT, and HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate (HR) (61.4 ± 9.0 bpm vs. 76.8 ± 13.6 bpm; P < 0.001) and a smaller [INCREMENT]HR during HUT (32.8 ± 10.5 bpm vs. 44.4 ± 13.3 bpm; P < 0.001). Time parameters increased in young and postural tachycardia syndrome during HRDB, which was characterized by a nonsignificant difference in [INCREMENT]HR between both groups. Time parameters were significantly higher in healthy old versus neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During HUT, only the SD of all normal RR intervals remained significantly higher. Heart rate changes corroborated these findings. Resting HR was significantly lower in healthy older (62.6 ± 11.0 bpm vs. 70.7 ± 12.4 bpm), and [INCREMENT]HR during HRDB was significantly higher (15.9 ± 9.2 bpm vs. 3.9 ± 4.2 bpm; P < 0.001). During HUT, [INCREMENT]HR showed no significant differences. Time domain parameters of heart rate variability have a greater utility than frequency parameters in clinical autonomic disorders.

Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

PubMed

Haapaniemi, T H; Pursiainen, V; Korpelainen, J T; Huikuri, H V; Sotaniemi, K A; Myllylä, V V

2001-03-01

Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

Cardiac and autonomic nerve function after reduced-intensity stem cell transplantation for hematologic malignancy in patients with pre-transplant cardiac dysfunction.

PubMed

Nakane, Takahiko; Nakamae, Hirohisa; Muro, Takashi; Yamagishi, Hiroyuki; Kobayashi, Yoshiki; Aimoto, Mizuki; Sakamoto, Erina; Terada, Yoshiki; Nakamae, Mika; Koh, Ki-Ryang; Yamane, Takahisa; Yoshiyama, Minoru; Hino, Masayuki

2009-09-01

Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe aplastic anemia is reversible after reduced-intensity allogeneic stem-cell transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve function to determine whether cardiac dysfunction due to causes other than hemochromatosis is attenuated after RIST. In five patients with cardiac dysfunction before transplant, we analyzed the changes in cardiac and autonomic nerve function after transplant, using electrocardiography (ECG), echocardiography, radionuclide angiography (RNA), serum markers, and heart rate variability (HRV), before and up to 100 days after transplant. There was no significant improvement in cardiac function in any patient and no significant alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the coefficient of variation of the RR interval (CVRR) decreased significantly 30 and 60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on frequency-domain analysis of HRV, low and high frequency power (LF and HF) significantly and temporarily decreased (P = 0.003 and 0.03, respectively). Notably, in one patient who had acute heart failure after transplantation, the values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation were the lowest of all the patients. In conclusion, this study suggests that (a) RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect improvement in cardiac dysfunction due to causes other than hemochromatosis; and (b) monitoring HRV may be useful in predicting cardiac events after RIST.

Takotsubo-like Myocardial Dysfunction in a Patient with Botulism.

PubMed

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-11-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease.

Takotsubo-like Myocardial Dysfunction in a Patient with Botulism

PubMed Central

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-01-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease. PMID:28924131

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

PubMed

Graziani, Alessandro; Casalini, Pierpaolo; Mirici-Cappa, Federica; Pezzi, Giuseppe; Giuseppe Stefanini, Francesco

2016-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Genetic autonomic disorders.

PubMed

Axelrod, Felicia B

2013-03-01

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

Balance of autonomic nervous system in children having signs of endothelial dysfunction, that were born and are domiciled in contaminated territories.

PubMed

Kondrashova, V G; Kolpakov, I E; Vdovenko, V Yu; Leonovych, O S; Lytvynets, O M; Stepanova, E I

2014-09-01

Objective. The study examined the features of functional state of the autonomic nervous system in children having endothelial dysfunction and permanently residing in contaminated areas. Materials and methods. Clinical and instrumental examination of 101 children aged 7-18 years that were born and are domiciled in contaminated territories, including 37 persons with signs of endothelial dysfunction (subgroup IA) and 64 ones with no signs of endothelial dysfunction (IB subgroup) was conducted. The control group being comparable to the subgroups IA and IB by age, gender and clinical examination results included 37 children neither been domiciled in contaminated areas nor were belonging to the contingent of Chornobyl accident survivors. There were 20 apparently healthy children also examined. Results. Due to peculiarities of physiological pathways providing adaptive responses the children having signs of endothelial dysfunction are characterized by a more pronounced dysregulation of autonomous nervous system both in a resting state and under a functional load simulation, and also by a high strain of adaptation pathways. The lack of autonomous support of cardiovascular system is caused by inadequate adaptive responses of both central regulatory bodies (hypothalamus, vasomotor center) and peripheral receptors. Mainly the failure of segmental autonomous (parasympathetic) structures was revealed. The mode of their response to stress in this case corresponds to that in healthy individuals but at a lower functional level. There is a reduced aerobic capacity of the organism by the Robinson index, contributing to low adaptive range to non-specific stress in children being domiciled on contaminated territories including children having the endothelial dysfunction. Conclusions. Endothelial dysfunction was associated with more pronounced manifestations of autonomic dysregulation and reduced aerobic capacity of the organism being the risk factors of development of a range of somatic diseases requiring the development of prevention measures in children permanently residing in contaminated areas. autonomous nervous system balance, endothelial dysfunction, children, Chornobyl accident. V. G. Kondrashova, I. E. Kolpakov, V. Yu. Vdovenko, O. S. Leonovych, O. M. Lytvynets, E. I. Stepanova.

Autonomic symptoms following Zika virus infection.

PubMed

Rodríguez, Yhojan; Rojas, Manuel; Ramírez-Santana, Carolina; Acosta-Ampudia, Yeny; Monsalve, Diana M; Anaya, Juan-Manuel

2018-04-01

To determine if autonomic symptoms are associated with previous Zika virus infection. Case-control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31). Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001). Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.

Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus.

PubMed

Weston, Kassia S; Sacre, Julian W; Jellis, Christine L; Coombes, Jeff S

2013-01-01

The purpose of this study was to compare the presence and severity of autonomic dysfunction in type 2 diabetes mellitus patients, with and without exaggerated blood pressure responses to exercise. We performed a cross-sectional analysis of 98 patients with type 2 diabetes mellitus (aged 59±9). Both time (standard deviation of RR intervals, root-mean-square of successive RR interval differences) and frequency (total spectral power, high frequency, low frequency, very low frequency) domains of heart rate variability were analysed in a 5 min recording at rest and 20 min after a maximal treadmill test. An exaggerated blood pressure response to exercise was identified by peak blood pressure ≥190/105 mmHg (women) or ≥210/105 mmHg (men). Each group of either exaggerated exercise blood pressure response or normal blood pressure response consisted of 49 patients. At rest there were no significant differences between groups for all time and frequency domain parameters of heart rate variability. Post-exercise, there was a significant (p<0.05) reduction in the SDNN, RMSSD and TP in the exaggerated exercise blood pressure group. Independent correlates (p<0.01) of exercise systolic blood pressure included post-exercise TP, resting systolic blood pressure, cardiac autonomic neuropathy and beta-blockers (beta=-0.28, adj. R² = 0.32, p<0.001). Reduced post-exercise heart rate variability in patients with type 2 diabetes mellitus, with an exaggerated exercise blood pressure response suggests preclinical autonomic dysfunction characterized by impaired vagal modulation. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Management of tetanus complication

NASA Astrophysics Data System (ADS)

Somia, I. K. A.

2018-03-01

The mortality rate of tetanus is still high; it is because of various complications due to muscle spasms, autonomic dysfunction, as well as due to prolonged critical care. Management of tetanus with its complications is in intensive care facilities. Management goals include stopping toxin production, neutralization of unbound toxin, management of the airway, muscle spasm control, treatment of autonomic dysfunction and general supportive management. Currently, diazepam is still an effective medication to control of muscle spasm and rigidity. Therapy for autonomic dysfunction that supported by evidence is MgSO4. Also, general supportive management for long-term care remains necessary to prevent other complications such as thromboembolism, infection, malnutrition, and others.

Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

PubMed Central

Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

2015-01-01

Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a “diffuse sensory organ” that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this “pan-endocrine illness” is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death. PMID:25763364

Autonomic dysfunction with early respiratory syncytial virus-related infection.

PubMed

Stock, Claire; Teyssier, Georges; Pichot, Vincent; Goffaux, Philippe; Barthelemy, Jean-Claude; Patural, Hugues

2010-08-25

Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (alpha LF, alpha HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group (p<0.05). RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring. Copyright 2010 Elsevier B.V. All rights reserved.

[Signs and symptoms of autonomic dysfunction in dysphonic individuals].

PubMed

Park, Kelly; Behlau, Mara

2011-01-01

To verify the occurrence of signs and symptoms of autonomic nervous system dysfunction in individuals with behavioral dysphonia, and to compare it with the results obtained by individuals without vocal complaints. Participants were 128 adult individuals with ages between 14 and 74 years, divided into two groups: behavioral dysphonia (61 subjects) and without vocal complaints (67 subjects). It was administered the Protocol of Autonomic Dysfunction, containing 46 questions: 22 related to the autonomic nervous system and had no direct relationship with voice, 16 related to both autonomic nervous system and voice, six non-relevant questions, and two reliability questions. There was a higher occurrence of reported neurovegetative signs in the group with behavioral dysphonia, in questions related to voice, such as frequent throat clearing, frequent swallowing need, fatigability when speaking, and sore throat. In questions not directly related to voice, dysphonic individuals presented greater occurrence of three out of 22 symptoms: gas, tinnitus and aerophagia. Both groups presented similar results in questions non-relevant to the autonomic nervous system. Reliability questions needed reformulation. Individuals with behavioral dysphonia present higher occurrence of neurovegetative signs and symptoms, particularly those with direct relationship with voice, indicating greater lability of the autonomic nervous system in these subjects.

Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists

PubMed Central

Abdala, Ana P.; Bissonnette, John M.; Newman-Tancredi, Adrian

2014-01-01

Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) “biased agonists.” We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. PMID:24910619

Basic Science Evidence for the Link Between Erectile Dysfunction and Cardiometabolic Dysfunction

PubMed Central

Musicki, Biljana; Bella, Anthony J.; Bivalacqua, Trinity J.; Davies, Kelvin P.; DiSanto, Michael E.; Gonzalez-Cadavid, Nestor F.; Hannan, Johanna L.; Kim, Noel N.; Podlasek, Carol A.; Wingard, Christopher J.; Burnett, Arthur L.

2016-01-01

Introduction Although clinical evidence supports an association between cardiovascular/metabolic diseases (CVMD) and erectile dysfunction (ED), scientific evidence for this link is incompletely elucidated. Aim This study aims to provide scientific evidence for the link between CVMD and ED. Methods In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current literature on basic scientific support for a mechanistic link between ED and CVMD, and deficiencies in this regard with a critical assessment of current preclinical models of disease. Results A link exists between ED and CVMD on several grounds: the endothelium (endothelium-derived nitric oxide and oxidative stress imbalance); smooth muscle (SM) (SM abundance and altered molecular regulation of SM contractility); autonomic innervation (autonomic neuropathy and decreased neuronal-derived nitric oxide); hormones (impaired testosterone release and actions); and metabolics (hyperlipidemia, advanced glycation end product formation). Conclusion Basic science evidence supports the link between ED and CVMD. The Committee also highlighted gaps in knowledge and provided recommendations for guiding further scientific study defining this risk relationship. This endeavor serves to develop novel strategic directions for therapeutic interventions. PMID:26646025

Cardiovascular dysfunction following spinal cord injury

PubMed Central

Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.

2016-01-01

Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative – once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance. PMID:27073353

Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction.

PubMed

Vincent, Ann; Whipple, Mary O; Low, Phillip A; Joyner, Michael; Hoskin, Tanya L

2016-05-01

Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia; however, no study to date has assessed these variables simultaneously with comprehensive measures. To characterize physical fitness and autonomic function with the use of clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Cross-sectional, observational, controlled study. Community sample of patients with fibromyalgia and healthy controls. Thirty patients with fibromyalgia and 30 pain and fatigue-free controls. Participants completed a battery of self-report questionnaires and physiological measures, including clinically validated measures of physical fitness and autonomic function. Six-Minute Walk Test total distance, maximal oxygen consumption as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire, and self-reported autonomic symptoms via the 31-item Composite Autonomic Symptom Score questionnaire. Autonomic function, as assessed by self-report, was significantly different between patients and controls (P < .0001); in contrast, the only difference between patients and controls on the Autonomic Reflex Screen was in the adrenergic domain (P = .022), and these abnormalities were mild. Self-reported physical activity was not significantly different between patients and controls (P = .99), but levels of moderate and vigorous physical activity as measured by actigraphy were significantly lower in patients (P = .012 and P = .047, respectively). Exercise capacity (6-Minute Walk) was poorer in patients (P = .0006), but there was no significant difference in maximal volume of oxygen consumption (P = .07). Patients with fibromyalgia report more severe symptoms across all domains, including physical activity and autonomic symptoms, compared with controls, but the objective assessments only showed modest differences. Our results suggest that patients with widespread subjective impairment of function have only modest objective measures of autonomic dysfunction. We recommend that the primary treatment goal should be focused on restoration of function, which may also ameliorate symptoms. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Patients with Fibromyalgia Have Significant Autonomic Symptoms but Modest Autonomic Dysfunction

PubMed Central

Vincent, Ann; Whipple, Mary O.; Low, Phillip A.; Joyner, Michael; Hoskin, Tanya L.

2015-01-01

Background Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia, however no study to date has simultaneously assessed these variables utilizing comprehensive measures. Objective To characterize physical fitness and autonomic function using clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Design Cross-sectional, observational, controlled study Setting Community sample of patients with fibromyalgia and healthy controls Participants 30 patients with fibromyalgia and 30 pain and fatigue-free controls Methods: Participants completed a battery of self-report questionnaires and physiological measures including clinically validated measures of physical fitness and autonomic function. Main Outcome Measurements 6 Minute Walk Test total distance, VO2 max as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire and self-reported autonomic symptoms using the 31-item Composite Autonomic Symptom Score questionnaire. Results Autonomic function, as assessed by self-report, was significantly different between patients and controls (p<.0001); in contrast, the only difference between patients and controls on the Autonomic Reflex Screen was in the adrenergic domain (p=.022), and these abnormalities were mild. Self-reported physical activity was not significantly different between patients and controls (p=.99), but levels of moderate and vigorous physical activity as measured by actigraphy, were significantly lower in patients (p=.012 and p=.047, respectively). Exercise capacity (6 Minute Walk) was poorer in patients (p=.0006), but there was no significant difference in maximal volume of oxygen consumption (p=.07). Conclusions Patients with fibromyalgia report more severe symptoms across all domains including physical activity and autonomic symptoms when compared to controls, but the objective assessments only showed modest differences. Our results suggest that patients with widespread subjective impairment of function have only modest objective measures of autonomic dysfunction. We recommend that the primary treatment goal should be focused on restoration of function which may also ameliorate symptoms. PMID:26314231

Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: a descriptive case report.

PubMed

Puliyel, Mammen M; Pillai, Rajappan; Korula, Sophy

2009-02-01

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.

Respiratory Sinus Arrhythmia Predicts Restricted Repetitive Behavior Severity

ERIC Educational Resources Information Center

Condy, Emma E.; Scarpa, Angela; Friedman, Bruce H.

2017-01-01

In addition to social communication deficits, restricted repetitive behaviors (RRBs) are a key diagnostic feature of autism spectrum disorder (ASD). Dysfunction of the autonomic nervous system (ANS) in ASD has been posited as a mechanism of RRBs; however, most studies investigating ANS activity in ASD have focused on its relation to social…

Animal model of neuropathic tachycardia syndrome

NASA Technical Reports Server (NTRS)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Autoantibody-mediated bowel and bladder dysfunction in a patient with chronic, nondiabetic neuropathy.

PubMed

Jackson, Michael W; Gordon, Thomas P; McCombe, Pamela A

2008-04-01

Physiological techniques can be used to detect novel autoantibodies causing alteration of autonomic function after passive transfer to mice. Previously, such antibodies have been detected in patients with type I diabetes mellitus, myasthenia gravis, and Sjogren's syndrome. We now describe a patient with an idiopathic nondiabetic neuropathy with prominent autonomic symptoms, including bladder and bowel dysfunction. Physiological assays of whole colon and bladder were used to determine the presence in the patient serum of functional autoantibodies capable of mediating autonomic dysfunction. Immunoglobulin G (IgG) from this patient was able to disrupt bladder and bowel function on passive transfer to mice. This is a new pattern of autoantibody-mediated abnormality. Although the target antigen is unknown, it is likely to be a cell-surface receptor or ion channel. This case highlights the usefulness of passive transfer studies in detecting functional antibodies in patients with autonomic neuropathy.

Clinical findings associated with cardiovascular autonomic dysfunction in adult sickle cell anaemia patients.

PubMed

Oguanobi, Nelson I; Onwubere, Basden J C; Anisiuba, Benedict C; Ike, Samuel O; Ejim, Emmanuel C; Ibegbulam, Obike G

2012-04-01

Involvement of the cardiovascular autonomic nervous system in various diseases is often associated with increased morbidity and mortality. The objective of this study was to examine the clinical features associated with cardiovascular autonomic neuropathy (CAN) in adult Nigerians with sickle cell anaemia. A cross-sectional study was carried out on 62 steady state sickle cell anaemia patients recruited from the adult out-patient clinic. Cardiovascular autonomic dysfunction was determined based on abnormal values in at least two of five non-invasive tests: Valsalva manoeuvre, heart rate variation during deep breathing, heart rate response to standing, blood pressure response to sustained handgrip, and blood pressure response to standing. All the subjects were initially evaluated in the clinic for symptoms of cardiovascular disease and peripheral vascular disease, and then clinically examined to assess their cardiovascular and neurological status at rest. Out of the 44 patients with cardiovascular autonomic neuropathy 23 were males, while 21 were females. The mean ages were 28.3 +/- 5.8 y for patients with CAN and 28.0 +/- 5.0 y for patients without CAN (P = 0.817). Sickle cell anaemia patients with CAN had significantly lower ankle systolic blood pressure, reduced ankle brachial blood pressure index, mean arterial blood pressure and haematocrit than patients without CAN. Of all the variables evaluated leg ulcers, postural dizziness, erectile dysfunction in men, and history of recurrent acute chest syndromes were found significantly more in patients with CAN than without. Clinical abnormalities tend to worsen with increasing degree of cardiovascular autonomic dysfunction. Significant cardiac morbidity is associated with abnormal cardiovascular autonomic function in sickle cell anaemia.

Methods of assessment of the post-exercise cardiac autonomic recovery: A methodological review.

PubMed

Peçanha, Tiago; Bartels, Rhenan; Brito, Leandro C; Paula-Ribeiro, Marcelle; Oliveira, Ricardo S; Goldberger, Jeffrey J

2017-01-15

The analysis of post-exercise cardiac autonomic recovery is a practical clinical tool for the assessment of cardiovascular health. A reduced heart rate recovery - an indicator of autonomic dysfunction - has been found in a broad range of cardiovascular diseases and has been associated with increased risks of both cardiac and all-cause mortality. For this reason, over the last several years, non-invasive methods for the assessment of cardiac autonomic recovery after exercise - either based on heart rate recovery or heart rate variability indices - have been proposed. However, for the proper implementation of such methods in daily clinical practice, the discussion of their clinical validity, physiologic meaning, mathematical formulation and reproducibility should be better addressed. Therefore, the aim of this methodological review is to present some of the most employed methods of post-exercise cardiac autonomic recovery in the literature and comprehensively discuss their strengths and weaknesses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How Facial Expressions in a Rett Syndrome Population Are Recognised and Interpreted by Those around Them as Conveying Emotions

ERIC Educational Resources Information Center

Bergstrom-Isacsson, Marith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2013-01-01

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions.…

Blood pressure normalization post-jugular venous balloon angioplasty.

PubMed

Sternberg, Zohara; Grewal, Prabhjot; Cen, Steven; DeBarge-Igoe, Frances; Yu, Jinhee; Arata, Michael

2015-05-01

This study is the first in a series investigating the relationship between autonomic nervous system dysfunction and chronic cerebrospinal venous insufficiency in multiple sclerosis patients. We screened patients for the combined presence of the narrowing of the internal jugular veins and symptoms of autonomic nervous system dysfunction (fatigue, cognitive dysfunction, sleeping disorders, headache, thermal intolerance, bowel/bladder dysfunction) and determined systolic and diastolic blood pressure responses to balloon angioplasty. The criteria for eligibility for balloon angioplasty intervention included ≥ 50% narrowing in one or both internal jugular veins, as determined by the magnetic resonance venography, and ≥ 3 clinical symptoms of autonomic nervous system dysfunction. Blood pressure was measured at baseline and post-balloon angioplasty. Among patients who were screened, 91% were identified as having internal jugular veins narrowing (with obstructing lesions) combined with the presence of three or more symptoms of autonomic nervous system dysfunction. Balloon angioplasty reduced the average systolic and diastolic blood pressure. However, blood pressure categorization showed a biphasic response to balloon angioplasty. The procedure increased blood pressure in multiple sclerosis patients who presented with baseline blood pressure within lower limits of normal ranges (systolic ≤ 105 mmHg, diastolic ≤ 70 mmHg) but decreased blood pressure in patients with baseline blood pressure above normal ranges (systolic ≥ 130 mmHg, diastolic ≥ 80 mmHg). In addition, gender differences in baseline blood pressure subcategories were observed. The coexistence of internal jugular veins narrowing and symptoms of autonomic nervous system dysfunction suggests that the two phenomena may be related. Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation. Further studies should investigate the association between blood pressure deviation and internal jugular veins narrowing, and whether blood pressure normalization affects Patient's clinical outcomes. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons.

PubMed

Thomas, Elizabeth A; Coppola, Giovanni; Tang, Bin; Kuhn, Alexandre; Kim, SoongHo; Geschwind, Daniel H; Brown, Timothy B; Luthi-Carter, Ruth; Ehrlich, Michelle E

2011-03-15

Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared with those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support. While genes related to excitotoxicity, dopamine signaling and trophic support were altered in both DE5 and R6/2 mice, which may be either cell autonomous or non-cell autonomous, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell-autonomous mechanisms. Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt, in the absence of expression in cortical neurons.

Autonomic Nervous System Disorders

MedlinePlus

Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

Dysfunction of autonomic nervous system in childhood obesity: a cross-sectional study.

PubMed

Baum, Petra; Petroff, David; Classen, Joseph; Kiess, Wieland; Blüher, Susann

2013-01-01

To assess the distribution of autonomic nervous system (ANS) dysfunction in overweight and obese children. Parasympathetic and sympathetic ANS function was assessed in children and adolescents with no evidence of impaired glucose metabolism by analysis of heart rate variability (low frequency power ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio, ratio of longest RR interval during expiration to shortest interval during inspiration (E/I ratio), root mean square of successive differences (RMSSD); sympathetic skin response (SSR); and quantitative pupillography (pupil diameter in darkness, light reflex amplitude, latency, constriction velocity, re-dilation velocity). The relationship of each ANS variable to the standard deviation score of body mass index (BMI-SDS) was assessed in a linear model considering age, gender and pubertal stage as co-variates and employing an F-statistic to compare the fit of nested models. Group comparisons between normal weight and obese children as well as an analysis of dependence on insulin resistance (as indexed by the Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) were performed for parameters shown to correlate with BMI-SDS. Statistical significance was set at 5%. Measurements were performed in 149 individuals (mean age 12.0 y; 90 obese 45 boys; 59 normal weight, 34 boys). E/I ratio (p = 0.003), ln(HF) (p = 0.03), pupil diameter in darkness (p = 0.01) were negatively correlated with BMI-SDS, whereas ln(LF/HF) was positively correlated (p = 0.05). Early re-dilation velocity was in trend negatively correlated to BMI-SDS (p = 0.08). None of the parameters that depended significantly on BMI-SDS was found to be significantly correlated with HOMA-IR. These findings demonstrate extended ANS dysfunction in obese children and adolescents, affecting several organ systems. Both parasympathetic activity and sympathetic activity are reduced. The conspicuous pattern of ANS dysfunction raises the possibility that obesity may give rise to dysfunction of the peripheral autonomic nerves resembling that observed in normal-weight diabetic children and adolescents.

[A not very essential obesity: the Rohhad syndrome. Description of two cases and review of the literature].

PubMed

Ramistella, V; Wasniewska, M; Valenzise, M; Corica, D; Cantucci, S; Pitrolo, E; Romeo, M; De Luca, F

2013-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Children typically show ROHHAD after the first years of life with rapid weight gain and subsequently autonomic nervous system dysregulation (altered pain perception, pupillary dysfunction, hypothermia and bradycardia); alveolar hypoventilation with risk of cardiorespiratory arrest and hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, growth hormone and corticotrophin deficiency). Tumours of neural crest origin, such as ganglioneuroblastoma and ganglioneuronoma, are reported in 33% of the patients and may be found in the chest or abdomen. Here we describe two girls who presented with rapid weight gain, at the age of 5 and 9 years respectively. The first was admitted due to obesity and central hypothyroidism. After two months she rapidly developed a clinical picture characterized by thermal dysregulation, hypodipsia and severe hypernatriemia, hypertrigliceridemia, alveolar hypoventilation supported by mechanical ventilation. The second presented with rapid-onset obesity and a mild hyperprolactinemia. After three months of follow-up she was admitted due to a clinical picture of hypothermia, seizures and hyponatremia. Subsequentely she developed altered water balance (severe hypernatremia) and severe hypoventilation. Chest CT and MR imaging showed a posterior mediastinal mass. Endocrinological investigation showed corticotrophin deficiency and central hypothyroidism treated with specific replacement therapies. On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome.

Cardiac Dysautonomia in Huntington's Disease.

PubMed

Abildtrup, Mads; Shattock, Michael

2013-01-01

Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

Vestibular autonomic regulation (including motion sickness and the mechanism of vomiting)

NASA Technical Reports Server (NTRS)

Balaban, C. D.

1999-01-01

Autonomic manifestations of vestibular dysfunction and motion sickness are well established in the clinical literature. Recent studies of 'vestibular autonomic regulation' have focused predominantly on autonomic responses to stimulation of the vestibular sense organs in the inner ear. These studies have shown that autonomic responses to vestibular stimulation are regionally selective and have defined a 'vestibulosympathetic reflex' in animal experiments. Outside the realm of experimental preparations, however, the importance of vestibular inputs in autonomic regulation is unclear because controls for secondary factors, such as affective/emotional responses and cardiovascular responses elicited by muscle contraction and regional blood pooling, have been inadequate. Anatomic and physiologic evidence of an extensive convergence of vestibular and autonomic information in the brainstem suggests though that there may be an integrated representation of gravitoinertial acceleration from vestibular, somatic, and visceral receptors for somatic and visceral motor control. In the case of vestibular dysfunction or motion sickness, the unpleasant visceral manifestations (e.g. epigastric discomfort, nausea or vomiting) may contribute to conditioned situational avoidance and the development of agoraphobia.

Close correlation of herpes zoster-induced voiding dysfunction with severity of zoster-related pain: A single faculty retrospective study.

PubMed

Fujii, Mizue; Takahashi, Ichiro; Honma, Masaru; Ishida-Yamamoto, Akemi

2015-11-01

Herpes zoster (HZ), a common vesiculo-erythematous skin disease associated with reactivation of varicella zoster virus in the cranial nerve, dorsal root, and autonomic ganglia, is accompanied by several related symptoms represented by postherpetic neuralgia. Among them, involvement of vesicorectal dysfunction is relatively rare. The vesicorectal symptom can usually be recovered in transient course, but is quite important in terms of impaired quality of life. Male individuals affected with HZ and skin lesions on sacral dermatome have been reported as independent risk factors of zoster-related voiding dysfunction. In this study, urinary symptoms were focused upon and six patients with zoster-related voiding dysfunction at a single faculty of dermatology in Japan from 2009 to 2014 were retrospectively analyzed. All patients showed HZ lesions on the sacral area and the urinary symptom recovered in approximately 2 months (14 days to 7 months). The term of treatment for zoster-associated urinary dysfunction was positively correlated with that for zoster-related pain without significance (r = 0.661, P = 0.153). Average treatment term for pain relief of sacral HZ accompanied by voiding dysfunction (91.3 ± 76.44 days) was significantly longer than that of sacral HZ without urinary symptom (18.9 ± 20.42 days) (P = 0.032). These results suggested that zoster-related voiding dysfunction would mainly be involved in sacral HZ and closely associated with severity of zoster-related pain. Dermatologists should be aware that severe zoster-related pain accompanied by sacral HZ, which is related to prolonged treatment of pain relief, can be a predictive factor of voiding dysfunction. © 2015 Japanese Dermatological Association.

Is There an Association Between Markers of Cardiovascular Autonomic Dysfunction at Discharge From Rehabilitation and Participation 1 and 5 Years Later in Individuals With Spinal Cord Injury?

PubMed

Rianne Ravensbergen, H J; de Groot, Sonja; Post, Marcel W; Bongers-Janssen, Helma M; van der Woude, Lucas H; Claydon, Victoria E

2016-09-01

To determine whether physical activity and participation 1 and 5 years after discharge are associated with measures of cardiovascular autonomic function: prevalence of hypotension and reduced peak heart rate at discharge from initial inpatient spinal cord injury (SCI) rehabilitation. Prospective cohort study. Rehabilitation centers. Individuals with SCI (N=146). Not applicable. We recorded markers of cardiovascular autonomic dysfunction (resting blood pressure and peak heart rate) and personal and lesion characteristics at the time of discharge from rehabilitation. Parameters for participation (social health status dimension of the Sickness Impact Profile) and physical activity (Physical Activity Scale for Individuals with Physical Disabilities [PASIPD]) were measured 1 and 5 years after discharge. Effects of prevalence of cardiovascular autonomic dysfunction were analyzed using linear regression analysis while correcting for possible confounders. We found no significant association between hypotension and social health status dimension of the Sickness Impact Profile or PASIPD, either at 1 or at 5 years after discharge. A significant association between peak heart rate and social health status dimension of the Sickness Impact Profile was found at 1 year after discharge, showing poorer participation in individuals with low peak heart rate (ie, cardiovascular autonomic dysfunction). The unadjusted relation between peak heart rate and the social health status dimension of the Sickness Impact Profile was significant at 5 years, but not when adjusted for confounders. We found associations between peak heart rate and PASIPD for both 1 and 5 years after discharge; however, these were not significant after correction for potential confounding factors. Autonomic dysfunction after SCI is a crucial factor influencing quality of life. We found that cardiovascular autonomic impairment, assessed from low peak heart rate, was associated with reduced participation after 1 year. The results suggest that peak heart rate at discharge from rehabilitation after SCI should be used to identify those needing additional support to facilitate physical activity and participation after discharge. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Memory dysfunction and autonomic neuropathy in non-insulin-dependent (type 2) diabetic patients.

PubMed

Zaslavsky, L M; Gross, J L; Chaves, M L; Machado, R

1995-11-01

Considering the nervous system as a unit, it might be expected that diabetic patients with autonomic neuropathy could have a central abnormality expressed as cognitive dysfunction. To determine whether autonomic neuropathy is independently associated with cognitive dysfunction, we studied a cross-section of 20 non-insulin-dependent diabetic patients with autonomic neuropathy (14 males and six females; age (mean) = 60 + or - 1 years); 29 non-insulin-dependent diabetic patients without autonomic neuropathy (14 males and 15 females; age = 59 + or - 1 years) and 34 non-diabetic patients (10 males and 24 females; age = 58 + or - 1 years), matched by age, education and duration of disease. Cognitive function was evaluated by tests of immediate, recent and remote memory: verbal (digit span; word span) and visual (recognition of towers and famous faces). Diabetic patients with autonomic neuropathy scored (median) lower in visual memory tests than diabetic patients without autonomic neuropathy and controls (towers immediate = 5 versus 7 and 6; towers recent = 4 versus 6 and 6; faces = 16 versus 18 and 18; respectively; Kruskal-Wallis; P < 0.05). There was no difference in verbal memory performance (Kruskal-Wallis; P > 0.05). Entering age, education, duration of disease and fasting plasma glucose in a stepwise multiple regression, the performance in these tests remained associated with autonomic neuropathy (towers immediate, P = 0.0054, partial r2 = 0.166; towers recent, P = 0.0076, partial r2 = 0.163). Scores in visual tests correlated negatively with the number of abnormal cardiovascular tests (faces, r = -0.25; towers recent, r = -0.24; Spearman; P < 0.05). Decreased visual cognitive function in non-insulin-dependent diabetic patients is associated with the presence and degree of autonomic neuropathy.

Autonomic Impairment in Borderline Personality Disorder: A Laboratory Investigation

ERIC Educational Resources Information Center

Weinberg, Anna; Klonsky, E. David; Hajcak, Greg

2009-01-01

Recent research suggests that emotional dysfunction in psychiatric disorders can be reflected in autonomic abnormalities. The present study examines sympathetic and parasympathetic autonomic nervous system activity in individuals with Borderline Personality Disorder (BPD) before, during, and following a social stressor task. Data were obtained…

Autonomic dysfunction in women with fibromyalgia

PubMed Central

2012-01-01

Fibromyalgia (FM) is an idiopathic disease characterized by widespread pain and a myriad of symptoms. Symptoms are diverse and include not only pain but also anxiety, depression, orthostatic intolerance, and cold intolerance. While the etiology of FM is not fully understood, data have suggested that FM may stem from dysfunction of the autonomic nervous system. This dysfunction has been reported at rest, and after a physiological stressor such as exercise. However, few studies have examined the responses during exercise. This novel approach may shed some new light on the effect of exercise in women with FM. PMID:22353700

Autonomic dysfunction assessed by EZSCAN and subclinical atherosclerosis.

PubMed

Sun, Jichao; Zhang, Yinfei; Xu, Baihui; Lv, Xiaofei; Ding, Lin; Chen, Ying; Sun, Wanwan; Lu, Jieli; Xu, Min; Bi, Yufang; Ning, Guang

2014-09-01

The present study aimed to explore the association between autonomic dysfunction and measurements of atherosclerosis in a middle-aged and elderly Chinese population. A population-based cross-sectional study was performed in Shanghai, China, from March to August 2010, with 5076 participants included in the analysis. Autonomic function was assessed by a novel EZSCAN test based on sudomotor function analysis. Carotid intima-media thickness (CIMT) was measured using B-mode ultrasonography and brachial-ankle pulse wave velocity (ba-PWV) was measured using an autonomic device. Participants were divided into three groups based on EZSCAN values: Group 1: EZSCAN 0-24; Group 2, EZSCAN 25-49; and Group 3, EZSCAN 50-100. These groups denoted autonomic dysfunction risk groups as follows: no risk, moderate risk and high risk, respectively. The prevalence of elevated CIMT and ba-PWV increased markedly with increasing EZSCAN values (elevated CIMT 7.4%, 17.5%, and 29.7%, elevated ba-PWV 3.2%, 19.7%, and 36.5%, in Groups 1, 2, and 3, respectively; both Ptrend < 0.0001). Logistic regressions revealed that EZSCAN values ≥50 were associated with a non-significantly higher risk of elevated CIMT (odds ratio [OR] = 1.43; 95% confidence interval [CI] 0.98-2.07) and a significantly higher risk of elevated ba-PWV (OR = 2.16; 95% CI 1.25-3.71) compared with EZSCAN values <25, after controlling for conventional risk factors. A higher EZSCAN value (≥50), an index of high autonomic dysfunction risk, was associated with an increased risk of elevated ba-PWV and CIMT. Such associations were partially explained by traditional atherosclerotic risk factors. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Some Non-FDA Approved Uses for Neuromodulation in Treating Autonomic Nervous System Disorders: A Discussion of the Preliminary Support.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-12-01

Neuromodulation, including cavernous nerve stimulation, gastric electrical stimulation, deep brain stimulation, and vagus nerve stimulation, has been used with success in treating several functional disease conditions. The FDA has approved the use of neuromodulation for a few indications. We discuss in our review article the evidence of using neuromodulation for treating some important disorders involving the autonomic nervous system that are not currently FDA approved. This was a review article that included a systematic online web search for human clinical studies testing the efficacy of neuromodulation in treating erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure. Our review includes all feasibility studies, nonrandomized clinical trials, and randomized controlled trials. Our systematic literature search found 3, 4, 5, 4, 1, and 4 clinical studies relating to erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure, respectively. This review article shows preliminary support based on clinical studies that neuromodulation can be of benefit for patients with important autonomic nervous system disease conditions that are not currently approved by the FDA. All of these investigational uses are encouraging; further studies are necessary and warranted for all indications discussed in this review before achieving FDA approval. © 2016 International Neuromodulation Society.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

PubMed Central

Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

2016-01-01

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; O'Callaghan, Chris; De Wandele, Inge; Stiles, Lauren; Pocinki, Alan; Rowe, Peter

2017-03-01

Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Exercise hemodynamics in Parkinson's disease and autonomic dysfunction.

PubMed

Low, David A; Vichayanrat, Ekawat; Iodice, Valeria; Mathias, Christopher J

2014-05-01

To clarify the characteristics of hemodynamic responses to exercise and orthostasis in Parkinson's disease patients, especially those with autonomic failure. Clinical audit of supine cycling exercise test data (with active standing tests pre- and post-exercise) of Parkinson's patients with autonomic dysfunction. 23 patients (71 ± 7 yr, 7 females) with a confirmed diagnosis of Parkinson's were identified. Group mean systolic blood pressure (SBP) fell during pre-exercise standing (-39 ± 29 mmHg, P < 0.001, 17 patients had orthostatic hypotension (OH)), while heart rate (HR) increased (+13 ± 7 beats min(-1), P < 0.001). SBP (P < 0.001) increased during exercise with a wide variation in responses. SBP increased in 13 patients (INC; +30 ± 14 mmHg) and either did not change or decreased in 10 patients (DEC -12 ± 11 mmHg, P < 0.001 vs INC). The increase in HR was not different between sub-groups (30 ± 12 vs 25 ± 10 beats min(-1), INC vs. DEC, P = 0.29). The size of the pre-exercise stand SBP reduction was greater in DEC vs INC (-64 ± 23 (10 out of 10 had OH) vs -19 ± 16 mmHg (7 out of 13 had OH), respectively, P < 0.001). The HR elevation was not different between sub-groups (13 ± 8 vs 13 ± 4 beats min(-1), DEC vs INC, P = 0.94). Post-exercise SBP/DBP were lower for both sub-groups compared to pre-exercise and the standing SBP reduction post-exercise was not greater relative to pre-exercise in either sub-group. Exercise-induced hypotension can occur in Parkinson's disease patients with autonomic failure with the magnitude of the exercise response being related to the severity of autonomic dysfunction. Exercise does not appear to worsen OH in this sample of Parkinson's patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome may have a hypothalamus-periaqueductal gray localization.

PubMed

Chow, Cristelle; Fortier, Marielle Valerie; Das, Lena; Menon, Anuradha P; Vasanwala, Rashida; Lam, Joyce C M; Ng, Zhi Min; Ling, Simon Robert; Chan, Derrick W S; Choong, Chew Thye; Liew, Wendy K M; Thomas, Terrence

2015-05-01

Anatomical localization of the rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome has proved elusive. Most patients had neuroimaging after cardiorespiratory collapse, revealing a range of ischemic lesions. A 15-year-old obese boy with an acute febrile encephalopathy had hypoventilation, autonomic dysfunction, visual hallucinations, hyperekplexia, and disordered body temperature, and saltwater regulation. These features describe the ROHHAD syndrome. Cerebrospinal fluid analysis showed pleocytosis, elevated neopterins, and oligoclonal bands, and serology for systemic and antineuronal antibodies was negative. He improved after receiving intravenous steroids, immunoglobulins, and long-term mycophenolate. Screening for neural crest tumors was negative. Magnetic resonance imaging of the brain early in his illness showed focal inflammation in the periaqueductal gray matter and hypothalamus. This unique localization explains almost all symptoms of this rare autoimmune encephalitis. Copyright © 2015 Elsevier Inc. All rights reserved.

Prediction of autonomic dysreflexia during urodynamics: a prospective cohort study.

PubMed

Walter, Matthias; Knüpfer, Stephanie C; Cragg, Jacquelyn J; Leitner, Lorenz; Schneider, Marc P; Mehnert, Ulrich; Krassioukov, Andrei V; Schubert, Martin; Curt, Armin; Kessler, Thomas M

2018-04-13

Autonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation. This prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation. We found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4-4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR 2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below. In patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications. ClinicalTrials.gov, NCT01293110 .

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide

PubMed Central

Rane, Shruti; McReynolds, Lisa J.; Steppan, Diana A.; Chen, Allen R.; Paz-Priel, Ido

2016-01-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. PMID:27313069

Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation.

PubMed

Yuan, Junhui; Matsuura, Eiji; Higuchi, Yujiro; Hashiguchi, Akihiro; Nakamura, Tomonori; Nozuma, Satoshi; Sakiyama, Yusuke; Yoshimura, Akiko; Izumo, Shuji; Takashima, Hiroshi

2013-04-30

To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses. On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease-causing genes and 5 related genes were screened using a next-generation sequencer. A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology. We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

PubMed Central

Newton, Julia L; Frith, James; Powell, Danielle; Hackett, Kate; Wilton, Katharine; Bowman, Simon; Price, Elizabeth; Pease, Colin; Andrews, Jacqueline; Emery, Paul; Hunter, John; Gupta, Monica; Vadivelu, Saravanan; Giles, Ian; Isenberg, David; Lanyon, Peter; Jones, Adrian; Regan, Marian; Cooper, Annie; Moots, Robert; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; McLaren, John; Young-Min, Steven; Dasgupta, Bhaskar; Griffiths, Bridget; Lendrem, Dennis; Mitchell, Sheryl; Ng, Wan-Fai

2012-01-01

Objectives To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS. Methods Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis. Results COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009). Conclusions Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity. PMID:22562982

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus

PubMed Central

Zhao, Jing-Bo; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr; Ejskjaer, Niels

2006-01-01

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Autonomic Dysfunction and Risk Factors Associated with Trypanosoma cruzi Infection among Children in Arequipa, Peru

PubMed Central

Bowman, Natalie M.; Kawai, Vivian; Gilman, Robert H.; Bocangel, Cesar; Galdos-Cardenas, Gerson; Cabrera, Lilia; Levy, Michael Z.; Cornejo del Carpio, Juan Geny; Delgado, Freddy; Rosenthal, Lauren; Pinedo-Cancino, Vivian V.; Steurer, Francis; Seitz, Amy E.; Maguire, James H.; Bern, Caryn

2011-01-01

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20–30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections. PMID:21212207

Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk.

PubMed

Myers, Kenneth A; Bello-Espinosa, Luis E; Symonds, Joseph D; Zuberi, Sameer M; Clegg, Robin; Sadleir, Lynette G; Buchhalter, Jeffrey; Scheffer, Ingrid E

2018-06-06

Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Nocturnal Anxiety in a Youth with Rapid-onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD).

PubMed

Grudnikoff, Eugene; Foley, Carmel; Poole, Claudette; Theodosiadis, Eva

2013-08-01

Behavioral and psychiatric disorders are common in youth with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD). We outline a rational approach to psychiatric treatment of a patient with a complex medical condition. We report the course of symptoms in a teen with ROHHAD, the inpatient treatment, and review current evidence for use of psychopharmacologic agents in youth with sleep and anxiety disturbances. A 14-year-old female began rapidly gaining weight as a preschooler, developed hormonal imbalance, and mixed sleep apnea. Consultation was requested after a month of ROHHAD exacerbation, with severe anxiety, insomnia, and auditory hallucinations. Olanzapine and citalopram were helpful in controlling the symptoms. Following discharge, the patient gained weight and olanzapine was discontinued. Lorazepam was started in coordination with pulmonary service. Relevant pharmacologic considerations included risk of respiratory suppression, history of paradoxical reaction to hypnotics, hepatic isoenzyme interactions and side effects of antipsychotics. Core symptoms of ROHHAD may precipitate psychiatric disorders. A systematic evidence-based approach to psychopharmacology is necessary in the setting of psychiatric consultation.

Nocturnal Anxiety in a Youth with Rapid-onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD)

PubMed Central

Grudnikoff, Eugene; Foley, Carmel; Poole, Claudette; Theodosiadis, Eva

2013-01-01

Objective: Behavioral and psychiatric disorders are common in youth with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD). We outline a rational approach to psychiatric treatment of a patient with a complex medical condition. Methods: We report the course of symptoms in a teen with ROHHAD, the inpatient treatment, and review current evidence for use of psychopharmacologic agents in youth with sleep and anxiety disturbances. Results: A 14-year-old female began rapidly gaining weight as a preschooler, developed hormonal imbalance, and mixed sleep apnea. Consultation was requested after a month of ROHHAD exacerbation, with severe anxiety, insomnia, and auditory hallucinations. Olanzapine and citalopram were helpful in controlling the symptoms. Following discharge, the patient gained weight and olanzapine was discontinued. Lorazepam was started in coordination with pulmonary service. Relevant pharmacologic considerations included risk of respiratory suppression, history of paradoxical reaction to hypnotics, hepatic isoenzyme interactions and side effects of antipsychotics. Conclusions: Core symptoms of ROHHAD may precipitate psychiatric disorders. A systematic evidence-based approach to psychopharmacology is necessary in the setting of psychiatric consultation. PMID:23970913

A Community Perspective on Bowel Management and Quality of Life after Spinal Cord Injury: The Influence of Autonomic Dysreflexia.

PubMed

Inskip, Jessica A; Lucci, Vera-Ellen M; McGrath, Maureen S; Willms, Rhonda; Claydon, Victoria E

2018-05-01

Autonomic dysfunction is common in individuals with spinal cord injury (SCI) and leads to numerous abnormalities, including profound cardiovascular and bowel dysfunction. In those with high-level lesions, bowel management is a common trigger for autonomic dysreflexia (AD; hypertension provoked by sensory stimuli below the injury level). Improving bowel care is integral for enhancing quality of life (QoL). We aimed to describe the relationships between bowel care, AD, and QoL in individuals with SCI. We performed an online community survey of individuals with SCI. Those with injury at or above T7 were considered at risk for AD. Responses were received from 287 individuals with SCI (injury levels C1-sacral and average duration of injury 17.1 ± 12.9 [standard deviation] years). Survey completion rate was 73% (n = 210). Bowel management was a problem for 78%: it interfered with personal relationships (60%) and prevented staying (62%) and working (41%) away from home. The normal bowel care duration was >60 min in 24% and most used digital rectal stimulation (59%); 33% reported bowel incontinence at least monthly. Of those at risk for AD (n = 163), 74% had AD symptoms during bowel care; 32% described palpitations. AD interfered with activities of daily living in 51%. Longer durations of bowel care (p < 0.001) and more severe AD (p = 0.04) were associated with lower QoL. Bowel management is a key concern for individuals with SCI and is commonly associated with symptoms of AD. Further studies should explore ways to manage bowel dysfunction, increase self-efficacy, and ameliorate the impact of AD to improve QoL.

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

PubMed Central

Khaleel, Maha; Sunwoo, John; Shah, Payal; Detterich, Jon A.; Kato, Roberta M.; Thuptimdang, Wanwara; Meiselman, Herbert J.; Sposto, Richard; Tsao, Jennie; Wood, John C.; Zeltzer, Lonnie; Coates, Thomas D.; Khoo, Michael C. K.

2017-01-01

Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BMv) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BMn-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BMn-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain. PMID:28542469

Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

PubMed

Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

2016-02-01

Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

PubMed

Jacobson, Lisa A; Rane, Shruti; McReynolds, Lisa J; Steppan, Diana A; Chen, Allen R; Paz-Priel, Ido

2016-07-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Copyright © 2016 by the American Academy of Pediatrics.

Impact of Pubertal Development and Physical Activity on Heart Rate Variability in Overweight and Obese Children in Taiwan

ERIC Educational Resources Information Center

Chen, Su-Ru; Chiu, Hung-Wen; Lee, Yann-Jinn; Sheen, Tzong-Chi; Jeng, Chii

2012-01-01

Child obesity is frequently associated with dysfunction of autonomic nervous system. Children in pubertal development were suggested to be vulnerable to autonomic nervous system problems such as decrease of heart rate variability from dysregulation of metabolic control. This study explored the influence of pubertal development on autonomic nervous…

Music and Autonomic Nervous System (Dys)function

PubMed Central

Ellis, Robert J.; Thayer, Julian F.

2010-01-01

Despite a wealth of evidence for the involvement of the autonomic nervous system (ANS) in health and disease and the ability of music to affect ANS activity, few studies have systematically explored the therapeutic effects of music on ANS dysfunction. Furthermore, when ANS activity is quantified and analyzed, it is usually from a point of convenience rather than from an understanding of its physiological basis. After a review of the experimental and therapeutic literatures exploring music and the ANS, a “Neurovisceral Integration” perspective on the interplay between the central and autonomic nervous systems is introduced, and the associated implications for physiological, emotional, and cognitive health are explored. The construct of heart rate variability is discussed both as an example of this complex interplay and as a useful metric for exploring the sometimes subtle effect of music on autonomic response. Suggestions for future investigations using musical interventions are offered based on this integrative account. PMID:21197136

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

PubMed

Wang, Ruihao; Hösl, Katharina M; Ammon, Fabian; Markus, Jörg; Koehn, Julia; Roy, Sankanika; Liu, Mao; de Rojas Leal, Carmen; Muresanu, Dafin; Flanagan, Steven R; Hilz, Max J

2018-06-01

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. In 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 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). 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. 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. Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Reversible autonomic dysfunction in hyperthyroid patients affects gastric myoelectrical activity and emptying.

PubMed

Barczyński, M; Thor, P

2001-08-01

The autonomic nervous system (ANS) function in hyperthyroidism has been so far investigated mainly from the cardiovascular point of view. The aim of this study is to show that the ANS dysfunction in hyperthyroidism is also expressed in gastric myoelectrical activity disturbances and gastric emptying disorders and to search for a correlation between the severity of clinical manifestation and free thyroid hormone levels and the degree of the ANS dysfunction. The analyzed group included 50 recently diagnosed patients with hyperthyroidism who were examined twice: before and after 3 months of thyrostatic treatment. Results were compared with those of a sex-, age- and BMI-matched control group of 50 healthy volunteers. The study included: heart rate variability analysis in time and frequency domain, at rest and during a deep-breathing test, surface electrogastrography in preprandial and postprandial periods measured simultaneously with the ultrasound assessment of gastric emptying time by Bolondi method. In patients with hyperthyroidism in comparison with the control group, the following significant differences were observed: a sharp reduction of the high-frequency component and a decrease of heart rate variability, a high incidence of dysrhythmia with dominant bradyarrhythmia, and a delay of gastric emptying. The degree of disorders related to the degree of clinical manifestation of hyperthyroidism's symptoms and free triiodothyronine serum concentration both. All the disorders were functional and disappeared in a stable euthyroidism. To conclude, the ANS dysfunction in hyperthyroidism results not only in withdrawal of vagal inhibitory effect on sinoatrial node, but in impaired mutual neuro-hormonal regulation (decrease of vagal influence) of gastric myoelectrical activity followed by delay of gastric emptying.

Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

PubMed

Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

2002-02-01

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

PubMed Central

Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity

PubMed Central

Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih

2014-01-01

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction. PMID:25541898

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity.

PubMed

Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih

2014-12-01

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.

Neurogenic bowel dysfunction: pathophysiology, clinical manifestations and treatment.

PubMed

Preziosi, Giuseppe; Emmanuel, Anton

2009-08-01

Bowel dysfunction (e.g., fecal incontinence, infrequent or difficult defecation) are both frequent and severely troubling problems for patients with spinal cord injury, multiple sclerosis and Parkinson's disease. The etiology of these symptoms is complex; there may be autonomic and pelvic nerve dysfunction (with attenuation of voluntary motor function and impaired anorectal sensation and anorectal reflexes), or generalized systemic factors (e.g., altered diet and behavior, impaired mobility, psychological disturbances or drug adverse effects). The mainstay of current treatment is adapting a conservative approach towards reversing the systemic effects and optimizing the mechanics of defecation through the use of laxatives and irrigation approaches. When successful, this approach improves both evacuation and incontinence symptoms, with associated improvements in quality of life and independence. Future therapies may be directed at modulating pelvic innervation through electrical stimulation. Stoma formation remains an option for patients refractory to other approaches.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

Central autonomic nervous system response to autonomic challenges is altered in patients with a previous episode of Takotsubo cardiomyopathy.

PubMed

Pereira, Vitor H; Marques, Paulo; Magalhães, Ricardo; Português, João; Calvo, Lucy; Cerqueira, João J; Sousa, Nuno

2016-04-01

Takotsubo cardiomyopathy is an intriguing disease characterized by acute transient left ventricular dysfunction usually triggered by an episode of severe stress. The excessive levels of catecholamines and the overactivation of the sympathetic system are believed to be the main pathophysiologic mechanisms of Takotsubo cardiomyopathy, but it is unclear whether there is a structural or functional signature of the disease. In this sense, our aim was to characterize the central autonomic system response to autonomic challenges in patients with a previous episode of Takotsubo cardiomyopathy when compared with a control group of healthy volunteers. Functional magnetic resonance imaging (fMRI) was performed in four patients with a previous episode of Takotsubo cardiomyopathy (average age of 67 ± 12 years) and in eight healthy volunteers (average age of 66 ± 5 years) while being submitted to different autonomic challenges (cold exposure and Valsalva manoeuvre). The fMRI analysis revealed a significant variation of the blood oxygen level dependent signal triggered by the Valsalva manoeuvre in specific areas of the brain involved in the cortical control of the autonomic system and significant differences in the pattern of activation of the insular cortex, amygdala and the right hippocampus between patients with Takotsubo cardiomyopathy and controls, even though these regions did not present significant volumetric changes. The central autonomic response to autonomic challenges is altered in patients with Takotsubo cardiomyopathy, thus suggesting a dysregulation of the central autonomic nervous system network. Subsequent studies are needed to unveil whether these alterations are causal or predisposing factors to Takotsubo cardiomyopathy. © The European Society of Cardiology 2015.

A Rare Cause of Hypothalamic Obesity, Rohhad Syndrome: 2 Cases.

PubMed

Şiraz, Ülkü Gül; Okdemir, Deniz; Direk, Gül; Akın, Leyla; Hatipoğlu, Nihal; Kendırcı, Mustafa; Kurtoğlu, Selim

2018-03-19

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease has not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. There are around 80 reported patients due to lack of recognition. We present two female patient suspected of ROHHAD due to weight gain since early childhood. The presented symptoms, respiratory and circulatory dysfunction, hypothalamic hypernatremia, hypothalamo-pituitary hormonal disorders such as santral hypothyrodism, hyperprolactinemia and santral early puberty are completely matched the criteria of ROHHAD syndrome. ROHHAD syndrome should be considered in differential diagnosis since it is difficult to distinguish from causes of monogenic obesity. Early identification of the disease reduces morbidity of the syndrome and patients require regular follow-up by a multidisciplinary approach.

Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux.

PubMed

Huang, Wan-Ju; Shu, Chih-Hung; Chou, Kun-Ta; Wang, Yi-Fen; Hsu, Yen-Bin; Ho, Ching-Yin; Lan, Ming-Ying

2013-06-01

The pathogenesis of laryngopharyngeal reflux (LPR) remains unclear. It is linked to but distinct from gastroesophageal reflux disease (GERD), which has been shown to be related to disturbed autonomic regulation. The aim of this study is to investigate whether autonomic dysfunction also plays a role in the pathogenesis of LPR. Case-control study. Tertiary care center. Seventeen patients with LPR and 19 healthy controls, aged between 19 and 50 years, were enrolled in the study. The patients were diagnosed with LPR if they had a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7. Spectral analysis of heart rate variability (HRV) analysis was used to assess autonomic function. Anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted. In HRV analysis, high frequency (HF) represents the parasympathetic activity of the autonomic nervous system, whereas low frequency (LF) represents the total autonomic activity. There were no significant differences in the LF power and HF power between the 2 groups. However, significantly lower HF% (P = .003) and a higher LF/HF ratio (P = .012) were found in patients with LPR, who demonstrated poor autonomic modulation and higher sympathetic activity. Anxiety was also frequently observed in the patient group. The study suggests that autonomic dysfunction seems to be involved in the pathogenesis of LPR. The potential beneficial effect of autonomic nervous system modulation as a therapeutic modality for LPR merits further investigation.

Limits of clinical tests to screen autonomic function in diabetes type 1.

PubMed

Ducher, M; Bertram, D; Sagnol, I; Cerutti, C; Thivolet, C; Fauvel, J P

2001-11-01

A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Heart Rate Variability Indexes in Dementia: A Systematic Review with a Quantitative Analysis.

PubMed

da Silva, Vanessa Pereira; Ramalho Oliveira, Bruno Ribeiro; Tavares Mello, Roger Gomes; Moraes, Helena; Deslandes, Andrea Camaz; Laks, Jerson

2018-01-01

Decreased heart rate variability (HRV) indexes indicate low vagal activity and may be associated with development of dementia. The neurodegenerative process is associated with the cardiovascular autonomic control. The aim of this systematic review was to investigate the effect size (ES) magnitude of the HRV indexes in the evaluation of autonomic dysfunction in older persons with dementia. PubMed (Medline), Web of Science, Scopus, Scielo, Lilacs, and APA Psycnet were consulted. Complete original articles published in English or Portuguese, investigating the association between autonomic dysfunction and dementia, using the HRV indexes were included. The search identified 97 potentially relevant articles. After screening the full text, eight articles were included in the qualitative analysis and six were included in the quantitative analysis. Almost all indexes showed a negative ES for all types of dementia and mild cognitive impairment. The most common frequency band of the power spectrum density function was the high frequency, which was reported by six studies. The meta-analysis of high frequency power in Alzheimer's disease group showed high heterogeneity and inconsistent results. The negative effect size suggests an autonomic dysfunction in all types of dementia as well as mild cognitive impairment. However, further analysis is necessary to support these results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Female Sexual Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington's Disease.

PubMed

Kolenc, Matej; Kobal, Jan; Podnar, Simon

2017-01-01

Although in Huntington's disease (HD) movement, cognition, and personality are most significantly affected, autonomic dysfunction should not be neglected. In women with HD sexual dysfunction has not been adequately studied yet. To report sexual dysfunction in a systematically studied cohort of female HD patients and compare it with controls of a similar age. In female HD patients and presymptomatic HD mutation carriers, we compared the Female Sexual Function Index (FSFI) questionnaire, neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC). Of 44 female HD patients and 9 presymptomatic HD mutation carriers, 30 HD patients and 8 HD mutation carriers responded our invitation to complete FFSI questionnaire. Finally, 23 HD women with a partner were compared to 47 controls with a partner. HD patients had more problems with sexual arousal, lubrication, orgasm and sexual satisfaction. By contrast, we found no difference in sexual desire and pain. Sexual dysfunction progressed in parallel with the decline in the TFC; severe sexual dysfunction occurred with TFC <7/13. Our study demonstrated a significant impact of HD on female sexual function that progressed with patients' functional decline and impaired patients' quality of life. Sexual dysfunction may be caused by progression of the disease itself, side effects of medication, and comorbidities like depression or dementia.

Impaired lung transfer factor in fibromyalgia syndrome.

PubMed

Rizzi, Maurizio; Atzeni, Fabiola; Airoldi, Andrea; Masala, Ignazio Francesco; Frassanito, Francesca; Salaffi, Fausto; Macaluso, Claudio; Sarzi-Puttini, Piercarlo

2016-01-01

The aim of this study was to evaluate whether pulmonary diffusing capacity is impaired in patients with fibromyalgia (FM) as it is in those with other diseases characterised by autonomic nerve system (ANS) dysfunction such as type 1 diabetes. Forty-five consecutive anti-nuclear antibody (ANA)-negative female Caucasian patients aged 50.1± 5.6 years with FM and compared with 45 healthy female control volunteers matched in terms of age and body mass index (BMI). The autonomic function has been evaluated by means of standard electrocardiography (ECG), finger blood pressure respiration, and muscle sympathetic nerve activity (MSNA) at rest and during a stepwise tilt test up to 75°. Their autonomic profiles were drawn up on the basis of MSNA, plasma catecholamine levels, and spectral indices of cardiac sympathetic and vagal modulation, and sympathetic vasomotor control computed by means of the spectrum analysis of RR and systolic arterial pressure (SAP) variability. Lung volumes and dynamic spirometry parameters were assessed by means of plethysmography. All of the patients were clinically evaluated and completed the FQI and COMPASS questionnaire. There was no difference in lung volumes between the FM patients and healthy controls, but DLCO (83±4 vs. 96±5; p<0.001), Kco (84±5 vs 98±5; p<0.001), DM (12.7±2.4 vs 13.6±1.8; p<0.05) and Vc (48±3.9 vs 65±7; p<0.001) were significantly reduced in the patients. The COMPASS-31, RCS and pain VAS scores significantly correlated with DLCO, Kco and Vc with the correlation being particularly close in the case of Vc. Furthermore, univariate Cox proportional hazard analysis showed that the three scores were all significantly associated with an increased risk of impaired DLCO (respectively, χ(2) 16.21, p<0.0005; χ(2) 7.09, p<0.005; χ(2) 6.37, p<0.01). FM impairs DLCO mainly as a result of a reduction in Vc, and that this defect is inversely proportional to the severity of the dysfunction suggesting a relationship between impaired DLCO and autonomic nerve dysfunction.

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

PubMed

Dimova, Rumyana; Tankova, Tsvetalina; Chakarova, Nevena

2017-09-01

Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and autonomic dysfunction. However, more patient-centered trials on the use of vitamin D supplementation in different conditions are needed. © 2017 American Society for Nutrition.

[THE CORRECTION WITH NOOPHEN OF AUTONOMIC DYSFUNCTION IN YOUNG MEN WITH HYPERTENSION].

PubMed

Knyazkova, I I; Kuzminova, N V; Osovskaya, N Yu

2015-01-01

The aim of this study was to investigate the influence of antihypertensive therapy with adding of gamma-amino-beta-phenylbutyric acid hydrochloride on the autonornic regulation of tcardiovascular system and the psychoemotional status in young men with hypertension. The study included 58 male with hypertension, aged 18-39 years (mean age 31.7 yearst 2.3 years), of them 28 patients (group I) administered beta-blocker and the other received a complex therapy which included beta-blocker and gamma-amino-beta-phenylbutyric acid hydrochiotide--Noofen ("OlainFarm", Latvia) 250 mg 3 times a day for 4 weeks. The control group consisted of 20 healthy indi&iduals aged 18-39 years (mean age 31.5 years +/- 2.5 years). The examination included of standard clinical; biochemical and instrumental investigatIons. We conducted a clinical measurement of blorid pressure, ambulatory blood pressure monitoring (ABPM), Doppler echocardiography, heart rate variability, autononlic symptoms questionnaire and Spielberger--Hanina Anxiety Scale. Analysis of circadian blbod pressure profile arid autonomic nervous system state in young men with hypertension, in spite of the short disenle history demonstratnl violations of the blood pressure circadian rhythm associated with the violation of the autonomic regulation of cardiovascular system as indreased sympathetic activity and decreased parasympathetic activity heart tate. In hypertensive patients with autonomic dysfunction we noted a reduction of level of mental health, which was reflected in an increase in'the number of people with high and moderate levels of reactive and personal anxiety It has been demonstratedthat the use of combination therapy with adding Noofen in young hypertensive men and autonomic dysfunction helped significantly improve the HRV parameters and restore autonomic balance on time parameters of heart rate variability reduced the level of reactive anxiety and imprdved the psychoemotional state.

[The prediction of atrial fibrillation recurrence after electrical cardioversion with the chemoreflex sensitivity].

PubMed

Budeus, M; Hennersdorf, M; Perings, C; Strauer, B E

2004-04-01

Patients with paroxysmal atrial fibrillation have a lower chemoreflex sensitivity (CHRS) which is characterized as an autonomic dysfunction. Because of this observation we examined the theory of an autonomic dysfunction as the reason for the reccurrence of atrial fibrilation after electrical cardioversion. We measured the CHRS among 43 patients 24 h after successful electrical cardioversion and the patients were controlled for at least 6 months. During the six months of follow-up a recurrence was observed in 18 patients with a mean of 8.3 days. There was no difference in organic heart disease or in the use of drugs. Left atrial diameter was not significantly larger in patients with a recurrence. Patients with a recurrence have a significantly lower CHRS than patients with sinus rhythm (2.41 +/- 1.82 vs 5.62 +/- 3.02 ms/mmHg, p < 0.04). The diagnostic value of a CHRS below 3.0 ms/mmHg achieved a specificity of 68%, a sensitivity of 67%, a positive and negative predictive value of 60% and 74%. An analysis of CHRS seems to be an appropriate method to predict a recurrence of atrial fibrillation. The predictive power of the method has to be examined by prospective investigations of a larger patient population and a longer follow-up. Patients with paroxysmal atrial fibrillation have a lower chemoreflex sensitivity (CHRS) which is characterized as an autonomic dysfunction. Because of this observation we examined the theory of an autonomic dysfunction as the reason for the recurrence of atrial fibrillation after electrical cardioversion.

Linear Analysis of Autonomic Activity and Its Correlation with Creatine Kinase-MB in Overt Thyroid Dysfunctions.

PubMed

Mavai, Manisha; Singh, Yogendra Raj; Gupta, R C; Mathur, Sandeep K; Bhandari, Bharti

2018-04-01

Autonomic activity may be deranged in thyroid dysfunctions and may lead to cardiovascular morbidity and mortality. Myopathy is a common manifestation in thyroid disorders and may be associated with raised serum creatine kinase (CK). We hypothesized that cardiovascular abnormality in thyroid dysfunction may manifest as raised CK-MB. This study was designed to investigate the correlation of CK and its isoform CK-MB with thyroid profile and linear parameters of heart rate variability (HRV). The study was conducted on 35 hypothyroid and hyperthyroid patients each, and 25 age-matched healthy controls. Autonomic activity was assessed by simple short term 5-min HRV. Biochemical evaluation of serum thyroid profile, CK-NAC and CK-MB were estimated in all the subjects. Our results demonstrated low HRV in hypo- as well as hyperthyroid patients. We observed significantly higher serum CK levels in hypothyroid patients when compared to hyperthyroids and controls. However, no significant differences were observed in CK-MB levels in the three groups. Significant positive correlation of CK with TSH and negative correlation with some HRV parameters (LF power, HF power, total power, SDNN, RMSSD) was observed in hypothyroid patients. Whereas correlation of CK-MB with thyroid profile as well as HRV parameters was non-significant in all the groups. Based on the CK and CK-MB findings and their correlation, we conclude that the cardiovascular changes seen in thyroid dysfunctions may primarily be due to autonomic imbalance without apparent cardiac muscle involvement. Whereas, raised CK levels indicate predominantly skeletal muscle involvement in hypothyroid patients.

Central- and autonomic nervous system coupling in schizophrenia

PubMed Central

Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

2016-01-01

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

Autonomic dysfunction affects cerebral neurovascular coupling.

PubMed

Azevedo, Elsa; Castro, Pedro; Santos, Rosa; Freitas, João; Coelho, Teresa; Rosengarten, Bernhard; Panerai, Ronney

2011-12-01

Autonomic failure (AF) affects the peripheral vascular system, but little is known about its influence on cerebrovascular regulation. Patients with familial amyloidotic polyneuropathy (FAP) were studied as a model for AF. Ten mild (FAPm), 10 severe (FAPs) autonomic dysfunction FAP patients, and 15 healthy controls were monitored in supine and sitting positions for arterial blood pressure (ABP) and heart rate (HR) with arterial volume clamping, and for blood flow velocity (BFV) in posterior (PCA) and contralateral middle cerebral arteries (MCA) with transcranial Doppler. Analysis included resting BFV, cerebrovascular resistance parameters (cerebrovascular resistance index, CVRi; resistance area product, RAP; and critical closing pressure, CrCP), and neurovascular coupling through visually evoked BFV responses in PCA (gain, rate time, attenuation, and natural frequency). In non-stimulation conditions, in each position, there were no significant differences between the groups, regarding HR, BP, resting BFV, and vascular resistance parameters. Sitting ABP was higher than in supine in the three groups, although only significantly in controls. Mean BFV was lower in sitting in all the groups, lacking statistical significance only in FAPs PCA. CVRi and CrCP increased with sitting in all the groups, while RAP increased in controls but decreased in FAPm and FAPs. In visual stimulation conditions, FAPs comparing to controls had a significant decrease of natural frequency, in supine and sitting, and of rate time and gain in sitting position. These results demonstrate that cerebrovascular regulation is affected in FAP subjects with AF, and that it worsens with orthostasis.

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

PubMed Central

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

[The clinical phenomenology of Rett's syndrome].

PubMed

Calderón-González, R; Calderón-Sepulveda, R F; Treviño-Welsh, J

1999-01-01

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

Brainstem dysfunction protects against syncope in multiple sclerosis.

PubMed

Habek, Mario; Krbot Skorić, Magdalena; Crnošija, Luka; Adamec, Ivan

2015-10-15

The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

[Investigation of the effects of cytoflavin on symptoms of depression and autonomic dysfunction in patients with organic depressive disorder].

PubMed

Gudkova, A N; Osinovskaia, N A; Polunina, A G; Gekht, A B

2013-01-01

The present observational study addressed effects of cytoflavin as an adjunctive nootropic therapy in patients with organic depressive disorder (F06.36). 54 female and 46 male in-patients were included into the study. All patients received standard antidepressant therapy (controls) and 48 patients additionally received 2 pills of cytoflavin twice per day. Age, gender distribution, education and severity of depression were equal in cytoflavin and control groups. The follow-up assessment at discharge showed a significantly more pronounced decline in the severity of depression symptoms in patients receiving cytoflavin in comparison with the controls. Importantly, the effect of cytoflavin on the depression symptoms was prominent only in females. Moreover, women receiving cytoflavin demonstrated the more pronounced normalization of autonomic regulation in comparison with control women. The present results allow to recommend cytoflavin in dose 4 pills daily as an adjunctive therapy in female patients with organic depressive disorder.

Idiopathic Hypersomnia.

PubMed

Trotti, Lynn Marie

2017-09-01

Idiopathic hypersomnia (IH) is a chronic neurologic disorder of daytime sleepiness, accompanied by long sleep times, unrefreshing sleep, difficulty in awakening, cognitive dysfunction, and autonomic symptoms. The cause is unknown; a genetic predisposition is suggested. Autonomic, inflammatory, or immune dysfunction has been proposed. Diagnosis involves a clinical history and objective testing. There are no approved treatments for IH, but modafinil is typically considered first-line. A substantial fraction of patients with IH are refractory or intolerant to standard treatments, and different treatment strategies using novel therapeutics are necessary. Even with current treatment options, quality of life and safety may remain impaired. Copyright © 2017 Elsevier Inc. All rights reserved.

[Treatment of functional somatic syndrome with abdominal pain].

PubMed

Abe, Tetsuya; Kanbara, Kenji; Mizuno, Yasuyuki; Fukunaga, Mikihiko

2009-09-01

Functional somatic syndrome (FSS) with abdominal pain include functional gastrointestinal disorder, chronic pancreatitis, chronic pelvic pain syndrome, which generally contain autonomic dysfunction. Regarding the treatment of FSS, it is important to know about FSS for a therapist at first. Secondly, the therapist should find out physical dysfunction of patients positively, and confirm objectively the hypotheses about both peripheral and central pathophysiological mechanisms as much as possible. Heart rate variability is an easy method, and useful to assess autonomic function. After grasping the patient's explanatory model about the illness, the therapist showes the most acceptable treatment for the patient at last.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease.

PubMed

Brudey, Chevelle; Park, Jeanie; Wiaderkiewicz, Jan; Kobayashi, Ihori; Mellman, Thomas A; Marvar, Paul J

2015-08-15

Stress- and anxiety-related disorders are on the rise in both military and general populations. Over the next decade, it is predicted that treatment of these conditions, in particular, posttraumatic stress disorder (PTSD), along with its associated long-term comorbidities, will challenge the health care system. Multiple organ systems are adversely affected by PTSD, and PTSD is linked to cancer, arthritis, digestive disease, and cardiovascular disease. Evidence for a strong link between PTSD and cardiovascular disease is compelling, and this review describes current clinical data linking PTSD to cardiovascular disease, via inflammation, autonomic dysfunction, and the renin-angiotensin system. Recent clinical and preclinical evidence regarding the role of the renin-angiotensin system in the extinction of fear memory and relevance in PTSD-related immune and autonomic dysfunction is also addressed. Copyright © 2015 the American Physiological Society.

Soluble TNFα Signaling within the Spinal Cord Contributes to the Development of Autonomic Dysreflexia and Ensuing Vascular and Immune Dysfunction after Spinal Cord Injury.

PubMed

Mironets, Eugene; Osei-Owusu, Patrick; Bracchi-Ricard, Valerie; Fischer, Roman; Owens, Elizabeth A; Ricard, Jerome; Wu, Di; Saltos, Tatiana; Collyer, Eileen; Hou, Shaoping; Bethea, John R; Tom, Veronica J

2018-04-25

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome. SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops after spinal cord injury (SCI) and is hallmarked by sudden, extreme hypertension, contributes to cardiovascular disease and susceptibility to infection, respectively, two leading causes of mortality and morbidity in SCI patients. We demonstrate that neuroinflammation-induced expression of soluble TNFα plays a critical role in AD, elucidating a novel underlying mechanism. We found that intrathecal administration after SCI of a biologic that inhibits soluble TNFα signaling dramatically attenuates AD and significantly reduces AD-associated peripheral vascular and immune dysfunction. We identified mechanisms behind diminished plasticity of neuronal populations within the spinal sympathetic reflex circuit. This study is the first to pinpoint a potential pharmacological, prophylactic strategy to attenuate AD and ensuing cardiovascular and immune dysfunction. Copyright © 2018 the authors 0270-6474/18/384147-17$15.00/0.

When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson's disease?

PubMed

De Luka, Silvio R; Svetel, Marina; Pekmezović, Tatjana; Milovanović, Branislav; Kostić, Vladimir S

2014-04-01

Dysautonomia appears in almost all patients with Parkinson's disease (PD) in a certain stage of their condition. The aim of our study was to detect the development and type of autonomic disorders, find out the factors affecting their manifestation by analyzing the potential association with demographic variables related to clinical presentation, as well as the symptoms of the disease in a PD patient cohort. The patients with PD treated at the Clinic of Neurology in Belgrade during a 2-year period, divided into 3 groups were studied: 25 de novo patients, 25 patients already treated and had no long-term levodopa therapy-related complications and 22 patients treated with levodopa who manifested levodopa-induced motor complications. Simultaneously, 35 healthy control subjects, matched by age and sex, were also analyzed. Autonomic nervous system malfunction was defined by Ewing diagnostic criteria. The tests, indicators of sympathetic and parasympathetic nervous systems, were significantly different in the PD patients as compared with the controls, suggesting the failure of both systems. However, it was shown, in the selected groups of patients, that the malfunction of both systems was present in two treated groups of PD patients, while de novo group manifested only sympathetic dysfunction. For this reason, the complete autonomic neuropathy was diagnosed only in the treated PD patients, while de novo patients were defined as those with the isolated sympathetic dysfunction. The patients with the complete autonomic neuropathy differed from the subjects without such neuropathy in higher cumulative and motor unified Parkinson's disease rating score (UPDRS) (p < 0.01), activities of daily living scores (p < 0.05), Schwab-England scale (p < 0.001) and Hoehn-Yahr scale. There was no difference between the patients in other clinical-demographic characteristics (sex, age at the time of diagnosis, actual age, duration of disease, involved side of the body, pain and freezing), but mini mental status (MMS) score and Hamilton depression and anxiety rating scale were significantly lower (p < 0.05). Our results confirm a high prevalence of autonomic nervous system disturbances among PD patients from the near onset of disease, with a predominant sympathetic nervous system involvement. The patients who developed complete autonomic neuropathy (both sympathetic and parasympathetic) were individuals with considerable level of functional failure, more severe clinical presentation and the existing anxiety and depression.

The Association between Central Adiposity and Autonomic Dysfunction in Obesity

PubMed Central

Fidan-Yaylali, Güzin; Yaylali, Yalin Tolga; Erdogan, Çağdaş; Can, Beray; Senol, Hande; Gedik-Topçu, Bengi; Topsakal, Senay

2016-01-01

Objective To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. Subjects and Methods The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. Results The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = −0.32; WC-HRR2: r = −0.31; WC-HRR3: r = −0.26; WC-HRR4: r = −0.23; WC-HRR5: r = −0.21; age-HRR2: r = −0.32; age-HRR3: r = −0.28; age-HRR4: r = −0.41; age-HRR5: r = −0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. Conclusion In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery. PMID:27194294

The crosstalk between autonomic nervous system and blood vessels

PubMed Central

Sheng, Yulan; Zhu, Li

2018-01-01

The autonomic nervous system (ANS), comprised of two primary branches, sympathetic and parasympathetic nervous system, plays an essential role in the regulation of vascular wall contractility and tension. The sympathetic and parasympathetic nerves work together to balance the functions of autonomic effector organs. The neurotransmitters released from the varicosities in the ANS can regulate the vascular tone. Norepinephrine (NE), adenosine triphosphate (ATP) and Neuropeptide Y (NPY) function as vasoconstrictors, whereas acetylcholine (Ach) and calcitonin gene-related peptide (CGRP) can mediate vasodilation. On the other hand, vascular factors, such as endothelium-derived relaxing factor nitric oxide (NO), and constriction factor endothelin, play an important role in the autonomic nervous system in physiologic conditions. Endothelial dysfunction and inflammation are associated with the sympathetic nerve activity in the pathological conditions, such as hypertension, heart failure, and diabetes mellitus. The dysfunction of the autonomic nervous system could be a risk factor for vascular diseases and the overactive sympathetic nerve is detrimental to the blood vessel. In this review, we summarize findings concerning the crosstalk between ANS and blood vessels in both physiological and pathological conditions and hope to provide insight into the development of therapeutic interventions of vascular diseases. PMID:29593847

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis

PubMed Central

Lin, Lian-Yu; Chang, Chin-Hao; Chu, Fang-Ying; Lin, Yen-Hung; Wu, Cho-Kai; Lee, Jen-Kuang; Hwang, Juei-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien

2016-01-01

Background and Objectives Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Materials and Methods Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. Results A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003). Conclusion Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID:26828209

Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype.

PubMed

Adamec, Ivan; Crnošija, Luka; Junaković, Anamari; Krbot Skorić, Magdalena; Habek, Mario

2018-06-04

To determine autonomic dysfunction (AD) differences in patients with relapsing remitting multiple sclerosis (pwRRMS) and progressive MS (pwPMS). Composite autonomic scoring scale (CASS) and heart rate variability (HRV) were performed in 40 pwRRMS and 30 pwPMS. pwPMS had a significantly higher sudomotor index and total CASS score compared to pwRRMS (p < 0.001 and p < 0.001, respectively). Disease duration positively correlated with sudomotor index and total CASS (r s  = 0.409, p < 0.001 and r s  = 0.472, p < 0.001, respectively), while the Expanded Disability Status Scale (EDSS) positively correlated with sudomotor index and total CASS (r s  = 0.411, p < 0.001 and r s  = 0.402, p = 0.001, respectively) in all patients. Type of multiple sclerosis (pwRRMS or pwPMS) corrected for age, sex and disease duration, was a statistically significant predictor of CASS value (B = 1.215, p = 0.019). Compared to pwRRMS, pwPMS had a significantly lower standard deviation of NN intervals (SDNN), low frequency (LF), and high frequency (HF), during both the supine and tilt-up phases (all p-values <0.006). pwPMS had a significantly lower LF/HF (p = 0.008) during tilt-up. There is a significant difference in autonomic function in pwRRMS and pwPMS; with pwPMS having a higher burden of AD, which is particularly evident for sweating dysfunction. Further research is needed to establish whether parasympathetic and sudomotor dysfunction may serve as markers of progressive MS. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

On heart rate variability and autonomic activity in homeostasis and in systemic inflammation.

PubMed

Scheff, Jeremy D; Griffel, Benjamin; Corbett, Siobhan A; Calvano, Steve E; Androulakis, Ioannis P

2014-06-01

Analysis of heart rate variability (HRV) is a promising diagnostic technique due to the noninvasive nature of the measurements involved and established correlations with disease severity, particularly in inflammation-linked disorders. However, the complexities underlying the interpretation of HRV complicate understanding the mechanisms that cause variability. Despite this, such interpretations are often found in literature. In this paper we explored mathematical modeling of the relationship between the autonomic nervous system and the heart, incorporating basic mechanisms such as perturbing mean values of oscillating autonomic activities and saturating signal transduction pathways to explore their impacts on HRV. We focused our analysis on human endotoxemia, a well-established, controlled experimental model of systemic inflammation that provokes changes in HRV representative of acute stress. By contrasting modeling results with published experimental data and analyses, we found that even a simple model linking the autonomic nervous system and the heart confound the interpretation of HRV changes in human endotoxemia. Multiple plausible alternative hypotheses, encoded in a model-based framework, equally reconciled experimental results. In total, our work illustrates how conventional assumptions about the relationships between autonomic activity and frequency-domain HRV metrics break down, even in a simple model. This underscores the need for further experimental work towards unraveling the underlying mechanisms of autonomic dysfunction and HRV changes in systemic inflammation. Understanding the extent of information encoded in HRV signals is critical in appropriately analyzing prior and future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

On heart rate variability and autonomic activity in homeostasis and in systemic inflammation

PubMed Central

Scheff, Jeremy D.; Griffel, Benjamin; Corbett, Siobhan A.; Calvano, Steve E.; Androulakis, Ioannis P.

2014-01-01

Analysis of heart rate variability (HRV) is a promising diagnostic technique due to the noninvasive nature of the measurements involved and established correlations with disease severity, particularly in inflammation-linked disorders. However, the complexities underlying the interpretation of HRV complicate understanding the mechanisms that cause variability. Despite this, such interpretations are often found in literature. In this paper we explored mathematical modeling of the relationship between the autonomic nervous system and the heart, incorporating basic mechanisms such as perturbing mean values of oscillating autonomic activities and saturating signal transduction pathways to explore their impacts on HRV. We focused our analysis on human endotoxemia, a well-established, controlled experimental model of systemic inflammation that provokes changes in HRV representative of acute stress. By contrasting modeling results with published experimental data and analyses, we found that even a simple model linking the autonomic nervous system and the heart confound the interpretation of HRV changes in human endotoxemia. Multiple plausible alternative hypotheses, encoded in a model-based framework, equally reconciled experimental results. In total, our work illustrates how conventional assumptions about the relationships between autonomic activity and frequency-domain HRV metrics break down, even in a simple model. This underscores the need for further experimental work towards unraveling the underlying mechanisms of autonomic dysfunction and HRV changes in systemic inflammation. Understanding the extent of information encoded in HRV signals is critical in appropriately analyzing prior and future studies. PMID:24680646

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

PubMed Central

Bernardi, L; Passino, C; Porta, C; Anesi, E; Palladini, G; Merlini, G

2002-01-01

Objective: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis. Design: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting. The values were subjected to spectral analysis to assess baroreflex sensitivity and the autonomic modulation of cardiac and vascular responses. Setting: Tertiary referral centre. Results: Autonomic modulation of the heart and blood pressure was nearly absent in the patients with amyloidosis: thus baroreflex sensitivity and the low frequency (0.1 Hz) fluctuations in all cardiovascular signals were severely reduced (p < 0.01 or more), as were respiratory fluctuations in the RR interval, and no change was observed upon tilting. Despite reduced autonomic modulation, blood pressure remained relatively stable in the amyloid group from supine to tilting. End tidal carbon dioxide was reduced in the amyloid patients (p < 0.001) indicating persistent hyperventilation; the breathing rate correlated inversely with the fall in blood pressure on tilting (p < 0.05). Conclusions: In primary amyloidosis, pronounced abnormalities in arterial baroreflexes and cardiovascular autonomic modulation to the heart and the vessels may be partly compensated for by hyperventilation at a slow breathing rate. PMID:12433892

Prevalence and pattern of cardiac autonomic dysfunction in newly detected type 2 diabetes mellitus.

PubMed

Jyotsna, Viveka P; Sahoo, Abhay; Sreenivas, V; Deepak, K K

2009-01-01

Cardiac autonomic functions were assessed in 145 consecutive recently detected type 2 diabetics. Ninety-nine healthy persons served as controls. Criteria for normalcy were, heart rate variation during deep breathing >or=15 beats/min, deep breathing expiratory to inspiratory R-R ratio >or=1.21, Valsalva ratio >or=1.21, sustained handgrip test >or=16 mm of mercury, cold pressor test >or=10, BP response to standing or=1.04. An abnormal test was defined as the above parameters being <10 beats/min, <1.21, <1.21, or=30 mm of mercury and

Pupillary and Heart Rate Reactivity in Children with Minimal Brain Dysfunction

ERIC Educational Resources Information Center

Zahn, Theodore P.; And Others

1978-01-01

In an attempt to replicate and extend previous findings on autonomic arousal and responsivity in children with minimal brain dysfunction (MBD), pupil size, heart rate, skin conductance, and skin temperature were recorded from 32 MBD and 45 control children (6-13 years old). (Author/CL)

Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device.

PubMed

Popok, David; West, Christopher; Frias, Barbara; Krassioukov, Andrei V

2016-07-29

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic level can lead to a potentially life-threatening hypertensive condition called autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious somatic or visceral stimuli below the level of injury. One of the most common triggers of AD is the distension of pelvic viscera, such as during bladder and bowel distension or evacuation. This protocol presents a novel pattern recognition algorithm developed for a JAVA platform software to study the fluctuations of cardiovascular parameters as well as the number, severity and duration of spontaneously occurring AD events. The software is able to apply a pattern recognition algorithm on hemodynamic data such as systolic blood pressure (SBP) and heart rate (HR) extracted from telemetry recordings of conscious and unrestrained animals before and after thoracic (T3) complete transection. With this software, hemodynamic parameters and episodes of AD are able to be detected and analyzed with minimal experimenter bias.

An anatomical and physiological basis for the cardiovascular autonomic nervous system consequences of sport-related brain injury.

PubMed

La Fountaine, Michael F

2017-11-29

Concussion is defined as a complex pathophysiological process affecting the brain that is induced by the application or transmission of traumatic biomechanical forces to the head. The result of the impact is the onset of transient symptoms that may be experienced for approximately 2weeks in most individuals. However, in some individuals, symptoms may not resolve and persist for a protracted period and a chronic injury ensues. Concussion symptoms are generally characterized by their emergence through changes in affect, cognition, or multi-sensory processes including the visual and vestibular systems. An emerging consequence of concussion is the presence of cardiovascular autonomic nervous system dysfunction that is most apparent through hemodynamic perturbations and provocations. Further interrogation of data that are derived from continuous digital electrocardiograms and/or beat-to-beat blood pressure monitoring often reveal an imbalance of parasympathetic or sympathetic nervous system activity during a provocation after an injury. The disturbance is often greatest early after injury and a resolution of the dysfunction occurs in parallel with other symptoms. The possibility exists that the disturbance may remain if the concussion does not resolve. Unfortunately, there is little evidence in humans to support the etiology for the emergence of this post-injury dysfunction. As such, evidence from experimental models of traumatic brain injury and casual observations from human studies of concussion implicate a transient abnormality of the anatomical structures and functions of the cardiovascular autonomic nervous system. The purpose of this review article is to provide a mechanistic narrative of multi-disciplinary evidence to support the anatomical and physiological basis of cardiovascular autonomic nervous system dysfunction after concussion. The review article will identify the anatomical structures of the autonomic nervous system and propose a theoretical framework to demonstrate the potential effects of concussive head trauma on corresponding outcome measurements. Evidence from experimental models will be used to describe abnormal cellular functions and provide a hypothetical mechanistic basis for the respective responses of the anatomical structures to concussive head trauma. When available, example observations from the human concussion literature will be presented to demonstrate the effects of concussive head trauma that may be related to anomalous activity in the respective anatomical structures of the autonomic nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Genital herpes simplex virus infections in adults.

PubMed

Mertz, G; Corey, L

1984-02-01

With the decline in prevalence of childhood-acquired oral-labial herpes simplex type 1 infections in some populations and the increasing incidence of genital herpes infections in adults, clinicians are more likely to see patients with severe primary, first-episode genital herpes infections. Complications of these primary infections may include aseptic meningitis and urine retention secondary to sacral radiculopathy or autonomic dysfunction. Presented are the clinical course of first-episode and recurrent infections, complications, diagnostic laboratory methods, and results of controlled clinical trials evaluating the efficacy of topical, intravenous, and oral preparations of acyclovir.

Cluster headache syndrome. Ways to abort or ward off attacks.

PubMed

Marks, D R; Rapoport, A M

1992-02-15

Cluster headache is a syndrome of severe head and facial pain accompanied by autonomic abnormalities. Men are affected more frequently than women. Headaches occur daily during periods of susceptibility, which may be followed by periods of remission. The etiology of cluster headache is uncertain. Recent work suggests that hypothalamic dysfunction and/or oxyhemoglobin desaturation may be involved in its pathogenesis. Effective medical regimens are available for aborting acute attacks and for preventing attacks. Surgical ablation of the trigeminal ganglion has been effective in some patients when conventional medical therapy has failed.

Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease.

PubMed

Shibao, Cyndya A; Kaufmann, Horacio

2017-11-01

Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

PubMed

Pistorio, Elisabetta; Luca, Maria; Luca, Antonina; Messina, Vincenzo; Calandra, Carmela

2011-10-28

To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

Recent advances in orthostatic hypotension presenting orthostatic dizziness or vertigo.

PubMed

Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

2015-11-01

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 % of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD.

Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease.

PubMed

Armao, Diane; Bailey, Rachel M; Bouldin, Thomas W; Kim, Yongbaek; Gray, Steven J

2016-08-01

Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood. Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice. Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice. For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care.

MSA Mimic? Rare Occurrence of Anti-Hu Autonomic Failure and Thymoma in a Patient with Parkinsonism: Case Report and Literature Review

PubMed Central

Ricigliano, Vito A. G.; Fossati, Barbara; Saraceno, Lorenzo; Cavalli, Michele; Bazzigaluppi, Elena; Meola, Giovanni

2018-01-01

Thymoma is a tumor originating from thymic gland, frequently manifesting with paraneoplastic neurological disorders. Its association with paraneoplastic dysautonomia is relatively uncommon. Here, we describe the challenging case of a 71 year-old female who developed subacute autonomic failure with digestive pseudo-obstruction, dysphagia, urinary tract dysfunction and orthostatic hypotension complicating an underlying extrapyramidal syndrome that had started 3 months before hospital admission. Autonomic symptoms had 2-month course and acutely worsened just before and during hospitalization. Combination of severe dysautonomia and parkinsonism mimicked rapidly progressing multiple system atrophy. However, diagnostic exams showed thymic tumor with positive anti-Hu antibodies on both serum and cerebrospinal fluid. Complete response of dysautonomia to immunoglobulins followed by thymectomy confirmed the diagnosis of anti-Hu-related paraneoplastic neurological syndrome. With regards to extrapyramidal symptoms, despite previous descriptions of paraneoplastic parkinsonism caused by other antineuronal antibodies, in our case no relation between anti-Hu and parkinsonism could be identified. A literature review of published reports describing anti-Hu positivity in thymic neoplasms highlighted that a definite autonomic disease due to anti-Hu antibodies is extremely rare in patients with thymoma but without myasthenia gravis, with only one case published so far. PMID:29416500

A Review of Cardiac Autonomic Measures: Considerations for Examination of Physiological Response in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Benevides, Teal W.; Lane, Shelly J.

2015-01-01

The autonomic nervous system (ANS) is responsible for multiple physiological responses, and dysfunction of this system is often hypothesized as contributing to cognitive, affective, and behavioral responses in children. Research suggests that examination of ANS activity may provide insight into behavioral dysregulation in children with autism…

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

PubMed

Hilz, Max J; Aurnhammer, Felix; Flanagan, Steven R; Intravooth, Tassanai; Wang, Ruihao; Hösl, Katharina M; Pauli, Elisabeth; Koehn, Julia

2015-11-15

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but increased BP upon EP, indicating a paradox sympathetic activation. The findings support the hypothesis that central autonomic dysfunction might contribute to an increased cardiovascular risk, even years after mTBI.

Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms, Maladaptations, and Management.

PubMed

Phillips, Aaron A; Krassioukov, Andrei V

2015-12-15

Cardiovascular (CV) issues after spinal cord injury (SCI) are of paramount importance considering they are the leading cause of death in this population. Disruption of autonomic pathways leads to a highly unstable CV system, with impaired blood pressure (BP) and heart rate regulation. In addition to low resting BP, on a daily basis the majority of those with SCI suffer from transient episodes of aberrantly low and high BP (termed orthostatic hypotension and autonomic dysreflexia, respectively). In fact, autonomic issues, including resolution of autonomic dysreflexia, are frequently ranked by individuals with high-level SCI to be of greater priority than walking again. Owing to a combination of these autonomic disturbances and a myriad of lifestyle factors, the pernicious process of CV disease is accelerated post-SCI. Unfortunately, these secondary consequences of SCI are only beginning to receive appropriate clinical attention. Immediately after high-level SCI, major CV abnormalities present in the form of neurogenic shock. After subsiding, new issues related to BP instability arise, including orthostatic hypotension and autonomic dysreflexia. This review describes autonomic control over the CV system before injury and the mechanisms underlying CV abnormalities post-SCI, while also detailing the end-organ consequences, including those of the heart, as well as the systemic and cerebral vasculature. The tertiary impact of CV dysfunction will also be discussed, such as the potential impediment of rehabilitation, and impaired cognitive function. In the recent past, our understanding of autonomic dysfunctions post-SCI has been greatly enhanced; however, it is vital to further develop our understanding of the long-term consequences of these conditions, which will equip us to better manage CV disease morbidity and mortality in this population.

Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease.

PubMed

Wang, Liqun; Xia, Jing; Li, Jonathan; Hagemann, Tracy L; Jones, Jeffrey R; Fraenkel, Ernest; Weitz, David A; Zhang, Su-Chun; Messing, Albee; Feany, Mel B

2018-05-15

Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. Further, we take cell biological and biophysical approaches to suggest that brain tissue stiffness is increased in Alexander disease. Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis.

Artificial neural network models for prediction of cardiovascular autonomic dysfunction in general Chinese population

PubMed Central

2013-01-01

Background The present study aimed to develop an artificial neural network (ANN) based prediction model for cardiovascular autonomic (CA) dysfunction in the general population. Methods We analyzed a previous dataset based on a population sample consisted of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN analysis. Performances of these prediction models were evaluated in the validation set. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with CA dysfunction (P < 0.05). The mean area under the receiver-operating curve was 0.762 (95% CI 0.732–0.793) for prediction model developed using ANN analysis. The mean sensitivity, specificity, positive and negative predictive values were similar in the prediction models was 0.751, 0.665, 0.330 and 0.924, respectively. All HL statistics were less than 15.0. Conclusion ANN is an effective tool for developing prediction models with high value for predicting CA dysfunction among the general population. PMID:23902963

Joint symbolic dynamics as a model-free approach to study interdependence in cardio-respiratory time series.

PubMed

Baumert, Mathias; Brown, Rachael; Duma, Stephen; Broe, G Anthony; Kabir, Muammar M; Macefield, Vaughan G

2012-01-01

Heart rate and respiration display fluctuations that are interlinked by central regulatory mechanisms of the autonomic nervous system (ANS). Joint assessment of respiratory time series along with heart rate variability (HRV) may therefore provide information on ANS dysfunction. The aim of this study was to investigate cardio-respiratory interaction in patients with Parkinson's disease (PD), a neurodegenerative disorder that is associated with progressive ANS dysfunction. Short-term ECG and respiration were recorded in 25 PD patients and 28 healthy controls during rest. To assess ANS dysfunction we analyzed joint symbolic dynamics of heart rate and respiration, cardio-respiratory synchrograms along with heart rate variability. Neither HRV nor cardio-respiratory synchrograms were significantly altered in PD patients. Symbolic analysis, however, identified a significant reduction in cardio-respiratory interactions in PD patients compared to healthy controls (16 ± 3.6 % vs. 20 ± 6.1 %; p= 0.02). In conclusion, joint symbolic analysis of cardio-respiratory dynamics provides a powerful tool to detect early signs of autonomic nervous system dysfunction in Parkinson's disease patients at an early stage of the disease.

Autonomic Nervous System in Paralympic Athletes with Spinal Cord Injury.

PubMed

Walter, Matthias; Krassioukov, Andrei V

2018-05-01

Individuals sustaining a spinal cord injury (SCI) frequently suffer from sensorimotor and autonomic impairment. Damage to the autonomic nervous system results in cardiovascular, respiratory, bladder, bowel, and sexual dysfunctions, as well as temperature dysregulation. These complications not only impede quality of life, but also affect athletic performance of individuals with SCI. This article summarizes existing evidence on how damage to the spinal cord affects the autonomic nervous system and impacts the performance in athletes with SCI. Also discussed are frequently used performance-enhancing strategies, with a special focus on their legal aspect and implication on the athletes' health. Copyright © 2018 Elsevier Inc. All rights reserved.

Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.

PubMed

Nomura, Atsushi; Kishimoto, Mitsumasa; Takahashi, Osamu; Deshpande, Gautam A; Yamaguchi, Kenichi; Okada, Masato

2014-05-01

Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.

Heart Rate Recovery and Variability Following Combined Aerobic and Resistance Exercise Training in Adults with and without Down Syndrome

ERIC Educational Resources Information Center

Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

2013-01-01

Persons with Down syndrome (DS) are at high risk for cardiovascular morbidity and mortality, and there is compelling evidence of autonomic dysfunction in these individuals. The main purpose of this study was to determine whether a combined aerobic and resistance exercise intervention produces similar results in cardiac autonomic function between…

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

PubMed

Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

2017-01-01

Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Involvement of Type 1 Angiontensin II Receptor (AT1) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors.

PubMed

Costa-Ferreira, Willian; Vieira, Jonas O; Almeida, Jeferson; Gomes-de-Souza, Lucas; Crestani, Carlos C

2016-01-01

Consistent evidence has shown an important role of emotional stress in pathogenesis of cardiovascular diseases. Additionally, studies in animal models have demonstrated that daily exposure to different stressor (heterotypic stressor) evokes more severe changes than those resulting from repeated exposure to the same aversive stimulus (homotypic stressor), possibly due to the habituation process upon repeated exposure to the same stressor. Despite these pieces of evidence, the mechanisms involved in the stress-evoked cardiovascular dysfunction are poorly understood. Therefore, the present study investigated the involvement of angiotensin II (Ang II) acting on the type 1 Ang II receptor (AT1) in the cardiovascular dysfunctions evoked by both homotypic and heterotypic chronic emotional stresses in rats. For this purpose, we compared the effect of the chronic treatment with the AT1 receptor antagonist losartan (30 mg/kg/day, p.o.) on the cardiovascular and autonomic changes evoked by the heterotypic stressor chronic variable stress (CVS) and the homotypic stressor repeated restraint stress (RRS). RRS increased the sympathetic tone to the heart and decreased the cardiac parasympathetic activity, whereas CVS decreased the cardiac parasympathetic activity. Additionally, both stressors impaired the baroreflex function. Alterations in the autonomic activity and the baroreflex impairment were inhibited by losartan treatment. Additionally, CVS reduced the body weight and increased the circulating corticosterone; however, these effects were not affected by losartan. In conclusion, these findings indicate the involvement of angiotensin II/AT1 receptors in the autonomic changes evoked by both homotypic and heterotypic chronic stressors. Moreover, the present results provide evidence that the increase in the circulating corticosterone and body weight reduction evoked by heterotypic stressors are independent of AT1 receptors.

Independent validation of the scales for outcomes in Parkinson's disease-autonomic (SCOPA-AUT).

PubMed

Rodriguez-Blazquez, C; Forjaz, M J; Frades-Payo, B; de Pedro-Cuesta, J; Martinez-Martin, P

2010-02-01

Autonomic dysfunction is common in Parkinson's disease (PD) and causes a great impact in health-related quality of life (HRQL) and functional status of patients. This study is the first independent validation of the Scales for Outcomes in PD-Autonomic (SCOPA-AUT). In an observational, cross-sectional study (ELEP Study), 387 PD patients were assessed using, in addition to the SCOPA-AUT, the Hoehn and Yahr staging, SCOPA-Motor, SCOPA-Cognition, Cumulative Illness Rating Scale-Geriatrics, modified Parkinson Psychosis Rating Scale, Clinical Impression of Severity Index for PD, Hospital Anxiety and Depression Scale, SCOPA-Sleep, SCOPA-Psychosocial, pain and fatigue visual analogue scales, and EQ-5D. SCOPA-AUT acceptability, internal consistency, construct validity, and precision were explored. Data quality was satisfactory (97%). SCOPA-AUT total score did not show floor or ceiling effect, and skewness was 0.40. Cronbach's alpha coefficients ranged from 0.64 (Cardiovascular and Thermorregulatory subscales) to 0.95 (Sexual dysfunction, women). Item homogeneity index was low (0.24) for Gastrointestinal subscale. Factor analysis identified eight factors for men (68% of the variance) and seven factors for women (65% of the variance). SCOPA-AUT correlated at a high level with specific HRQL and functional measures (r(S) = 0.52-0.56). SCOPA-AUT scores were higher for older patients, for more advanced disease, and for patients treated only with levodopa (Kruskal-Wallis test, P < 0.01). Standard error of measurement for SCOPA-AUT subscales was 0.81 (sexual, men) - 2.26 (gastrointestinal). Despite its heterogeneous content, which determines some weaknesses in the psychometric attributes of its subscales, SCOPA-AUT is an acceptable, consistent, valid and precise scale.

Cardiac autonomic neuropathy risk estimated by sudomotor function and arterial stiffness in Chinese subjects.

PubMed

Zeng, Q; Dong, S-Y; Wang, M-L; Wang, F; Li, J-M; Zhao, X-L

2016-11-01

The SUDOSCAN test was recently developed to detect diabetic autonomic neuropathy early and screen for cardiac autonomic neuropathy (CAN) through assessment of sudomotor function. The aim of this study was to investigate the relationship of cardiac autonomic dysfunction estimated by the SUDOSCAN test with arterial stiffness. A total of 4019 subjects without diabetes or established cardiovascular disease were tested with SUDOSCAN, central systolic blood pressure (cSBP) and brachial-ankle pulse wave velocity (baPWV). Hands mean electrochemical skin conductance (ESC) measured by SUDOSCAN was 70±17 μS, feet mean ESC was 71±16 μS and the CAN risk score was 21±10%. The levels of cSBP and baPWV increased across quartiles of CAN risk score (P for trend <0.001 for all). In spearman correlation analyses, the CAN risk score was positively correlated with cSBP (r=0.391, P<0.001) and baPWV (r=0.305, P<0.001). In multivariable analyses, the values of cSBP and baPWV increased 0.17 mm Hg (P=0.002) and 2.01 cm per second (P=0.010), respectively, when CAN risk score increased 1%. The results were unchanged when stratified by glucose tolerance status. In conclusion, cardiac autonomic dysfunction estimated by sudomotor function was correlated with arterial stiffness independent of conventional factors and glucose tolerance status.

Recent clinical advances in diabetic polyneuropathy.

PubMed

Horowitz, Steven H

2006-10-01

Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners. The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising. Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

Mitochondria and Cardiovascular Aging

PubMed Central

Dai, Dao-Fu; Ungvari, Zoltan

2013-01-01

Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

The characteristics of autonomic nervous system disorders in burning mouth syndrome and Parkinson disease.

PubMed

Koszewicz, Magdalena; Mendak, Magdalena; Konopka, Tomasz; Koziorowska-Gawron, Ewa; Budrewicz, Sławomir

2012-01-01

To conduct a clinical electrophysiologic evaluation of autonomic nervous system functions in patients with burning mouth syndrome and Parkinson disease and estimate the type and intensity of the autonomic dysfunction. The study involved 83 subjects-33 with burning mouth syndrome, 20 with Parkinson disease, and 30 controls. The BMS group included 27 women and 6 men (median age, 60.0 years), and the Parkinson disease group included 15 women and 5 men (median age, 66.5 years). In the control group, there were 20 women and 10 men (median age, 59.0 years). All patients were subjected to autonomic nervous system testing. In addition to the Low autonomic disorder questionnaire, heart rate variability (HRV), deep breathing (exhalation/inspiration [E/I] ratio), and sympathetic skin response (SSR) tests were performed in all cases. Parametric and nonparametric tests (ANOVA, Kruskal-Wallis, and Scheffe tests) were used in the statistical analysis. The mean values for HRV and E/I ratios were significantly lower in the burning mouth syndrome and Parkinson disease groups. Significant prolongation of SSR latency in the foot was revealed in both burning mouth syndrome and Parkinson disease patients, and lowering of the SSR amplitude occurred in only the Parkinson disease group. The autonomic questionnaire score was significantly higher in burning mouth syndrome and Parkinson disease patients than in the control subjects, with the Parkinson disease group having the highest scores. In patients with burning mouth syndrome, a significant impairment of both the sympathetic and parasympathetic nervous systems was found but sympathetic/parasympathetic balance was preserved. The incidence and intensity of autonomic nervous system dysfunction was similar in patients with burning mouth syndrome and Parkinson disease, which may suggest some similarity in their pathogeneses.

Hypocretin-1 deficiency in a girl with ROHHAD syndrome.

PubMed

Dhondt, Karlien; Verloo, Patrick; Verhelst, Hélène; Van Coster, Rudy; Overeem, Sebastiaan

2013-09-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and complex pediatric syndrome, essentially caused by dysfunction of 3 vital systems regulating endocrine, respiratory, and autonomic nervous system functioning. The clinical spectrum of ROHHAD is broad, but sleep/wake disorders have received relatively little attention so far, although the central hypothalamic dysfunction would make the occurrence of sleep symptoms likely. In this case report, we expand the phenotype of ROHHAD with a number of striking sleep symptoms that together can be classified as a secondary form of narcolepsy. We present a 7-year-old girl with ROHHAD who displayed the classic features of narcolepsy with cataplexy: excessive daytime sleepiness with daytime naps, visual hallucinations, and partial cataplexy reflected in intermittent loss of facial muscle tone. Nocturnal polysomnography revealed sleep fragmentation and a sleep-onset REM period characteristic for narcolepsy. The diagnosis was confirmed by showing an absence of hypocretin-1 in the cerebrospinal fluid. We discuss potential pathophysiological implications as well as symptomatic treatment options.

Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction.

PubMed

Maas, U; Strubelt, S

2006-01-01

Ibogaine is the most important alkaloid of the Central African Iboga-shrub. It is the central drug in Gabonian initiation ceremonies in which it is used to cause a near-death experience. In Western countries it is used in private clinics to treat addiction. However, in the United States and most European countries it is classified as an illegal drug because at least eight persons have died after having taken Ibogaine. These fatalities occurred in most cases several days after ingestion or following the intake of very small doses. There is no conclusive explanation at the present time for these deaths. We hypothesize, that these deaths may be a result of cardiac arrhythmias, caused by a dysregulation of the autonomic nervous system. Ibogaine affects the autonomic nervous system by influencing several neurotransmitter-systems and the fastigial nucleus. The cerebellar nucleus responds to small doses with a stimulation of the sympathetic system, leading to a fight or flight reaction. High doses, however, lead to a vagal dominance: a "feigned death". The risk of cardiac arrhythmias is increased in situations of sympathetic stimulation or coincidence of a high parasympathetic tonus and a left-sided sympathetic stimulation. This could occur under influence of small doses of ibogaine and also at times of exhaustion with a high vagal tonus, when sudden fear reactions could cause a critical left-sided sympathetic stimulation. Gabonian healers prevent these risks by isolating their patients from normal life and by inducing a trance-state with right-hemispheric and vagal dominance for several days.

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

PubMed Central

Jellinger, Kurt A.

2017-01-01

Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). While our knowledge of the molecular pathogenesis of this devastating disease is still incomplete, updated consensus criteria and combined fluid and imaging biomarkers have increased its diagnostic accuracy. The neuropathologic hallmark of this unique proteinopathy is the deposition of aberrant α-synuclein in both glia (mainly oligodendroglia) and neurons forming glial and neuronal cytoplasmic inclusions that cause cell dysfunction and demise. In addition, there is widespread demyelination, the pathogenesis of which is not fully understood. The pathogenesis of MSA is characterized by propagation of misfolded α-synuclein from neurons to oligodendroglia and cell-to-cell spreading in a “prion-like” manner, oxidative stress, proteasomal and mitochondrial dysfunction, dysregulation of myelin lipids, decreased neurotrophic factors, neuroinflammation, and energy failure. The combination of these mechanisms finally results in a system-specific pattern of neurodegeneration and a multisystem involvement that are specific for MSA. Despite several pharmacological approaches in MSA models, addressing these pathogenic mechanisms, no effective neuroprotective nor disease-modifying therapeutic strategies are currently available. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable biomarkers and targets for effective treatment of this hitherto incurable disorder is urgently needed. PMID:28984582

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

PubMed

Chu, Jennifer; Bruyninckx, Frans; Neuhauser, Duncan V

2017-07-01

Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.

Linear and Nonlinear Analyses of the Cardiac Autonomic Control in Children With Developmental Coordination Disorder: A Case-Control Study.

PubMed

Cavalcante Neto, Jorge L; Zamunér, Antonio R; Moreno, Bianca C; Silva, Ester; Tudella, Eloisa

2018-01-01

Children with Developmental Coordination Disorder (DCD) and children at risk for DCD (r-DCD) present motor impairments interfering in their school, leisure and daily activities. In addition, these children may have abnormalities in their cardiac autonomic control, which together with their motor impairments, restrict their health and functionality. Therefore, this study aimed to assess the cardiac autonomic control, by linear and nonlinear analysis, at supine and during an orthostatic stimulus in DCD, r-DCD and typically developed children. Thirteen DCD children (11 boys and 2 girls, aged 8.08 ± 0.79 years), 19 children at risk for DCD (13 boys and 6 girls, aged 8.10 ± 0.96 years) and 18 typically developed children, who constituted the control group (CG) (10 boys and 8 girls, aged 8.50 ± 0.96 years) underwent a heart rate variability (HRV) examination. R-R intervals were recorded in order to assess the cardiac autonomic control using a validated HR monitor. HRV was analyzed by linear and nonlinear methods and compared between r-DCD, DCD, and CG. The DCD group presented blunted cardiac autonomic adjustment to the orthostatic stimulus, which was not observed in r-DCD and CG. Regarding nonlinear analysis of HRV, the DCD group presented lower parasympathetic modulation in the supine position compared to the r-DCD and CG groups. In the within group analysis, only the DCD group did not increase HR from supine to standing posture. Symbolic analysis revealed a significant decrease in 2LV ( p < 0.0001) and 2UV ( p < 0.0001) indices from supine to orthostatic posture only in the CG. In conclusion, r-DCD and DCD children present cardiac autonomic dysfunction characterized by higher sympathetic, lower parasympathetic and lower complexity of cardiac autonomic control in the supine position, as well as a blunted autonomic adjustment to the orthostatic stimulus. Therefore, cardiovascular health improvement should be part of DCD children's management, even in cases of less severe motor impairment.

Abnormalities of the QT interval in primary disorders of autonomic failure.

PubMed

Choy, A M; Lang, C C; Roden, D M; Robertson, D; Wood, A J; Robertson, R M; Biaggioni, I

1998-10-01

Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

The physical examination as a window into autonomic disorders.

PubMed

Cheshire, William P; Goldstein, David S

2018-02-01

Signs of autonomic dysfunction, although at times seemingly mysterious, can contribute to diagnostic clarification and clinical investigation. Even when sophisticated autonomic testing equipment is not readily available, the experienced clinician, through educated observation and inductive reasoning-in conjunction with an intelligently obtained autonomic medical history-can discern much by a careful physical examination. Elements of the autonomic examination include variations in the pulse, postural measurements of blood pressure and heart rate, pupillary light reactions, skin coloration and temperature, patterns of sweating, and other organ-specific physical findings relevant to the individual patient's presentation. Especially important is the often neglected practice of measuring the blood pressure standing up, for orthostatic hypotension cannot be diagnosed by symptoms alone and is a common source of potential morbidity. The examination should be carried out in the context of understanding the syndromic nature of abnormalities of components of the autonomic nervous system.

Autonomic Neuropathy

MedlinePlus

... achieving or maintaining an erection (erectile dysfunction) or ejaculation problems in men. In women, problems include vaginal dryness, low libido and difficulty reaching orgasm. Difficulty digesting food, such as feeling full after ...

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study.

PubMed

Adams, Scott C; Schondorf, Ronald; Benoit, Julie; Kilgour, Robert D

2015-05-18

Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up. Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction - as a possible contributor to the pathogenesis of CV disease in cancer survivors.

Utility of Autonomic Function Tests to Differentiate Dementia with Lewy Bodies and Parkinson Disease with Dementia from Alzheimer Disease.

PubMed

Toru, Shuta; Kanouchi, Tadashi; Yokota, Takanori; Yagi, Yosuke; Machida, Akira; Kobayashi, Takayoshi

2018-01-01

We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Autonomic function tests might be quite useful to distinguish DLB and PDD from AD. © 2017 S. Karger AG, Basel.

Neurovascular and Autonomic Dysfunction Associated with Gulf War Illness Pain

DTIC Science & Technology

2016-10-01

pyridostigmine and organophosphorus pesticides with human cholinesterases." Chem Biol Interact 190(2-3): 79-83. Wilson, B. W., F. J. Rusli, M. K. Yan Tam...vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases." Chem Biol Interact 190(2-3): 79-83...that can accompany pain symptoms in veterans with GWI. 2. Keywords: pain, autonomic, nociceptor, blood flow, pesticides , pyridostigmine bromide

Neurovascular and Autonomic Dysfunction Associated with Gulf War Illness Pain

DTIC Science & Technology

2017-10-01

pesticides with human cholinesterases." Chem Biol Interact 190(2-3): 79-83. Wilson, B. W., J. D. Henderson, E. M. Coatney, P. S. Nieberg and P. S...Keywords: pain, autonomic, nociceptor, blood flow, pesticides , pyridostigmine bromide, DEET, Gulf War Illness 3. Accomplishments The SOW is...delayed onset joint, muscle and other deep tissue pain. The Research Advisory Committee on Gulf War Illness (GWI) has determined that pesticides may

[A role of the autonomic nervous system in cerebro-cardiac disorders].

PubMed

Basantsova, N Yu; Tibekina, L M; Shishkin, A N

The authors consider anatomical/physiological characteristics and a role of different autonomic CNS regions, including insula cortex, amygdala complex, anterior cingulate cortex, ventral medial prefrontal cortex, hypothalamus and epiphysis, involved in the regulation of cardiovascular activity. The damage of these structures, e.g., due to the acute disturbance of cerebral blood circulation, led to arrhythmia, including fatal arrhythmia, in previously intact myocardium; systolic and diastolic dysfunction, ischemic changes considered in the frames of cerebro-cardial syndrome. On the cellular level, the disturbance of autonomic regulation resulted in catechol amine excitotoxicity, oxidative stress and free radical myocardium injury.

An update of clinical management of acute intermittent porphyria

PubMed Central

Pischik, Elena; Kauppinen, Raili

2015-01-01

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. PMID:26366103

ROHHAD in a 9-year-old boy — clinical case.

PubMed

Kot, Karolina; Moszczyńska, Elżbieta; Lecka-Ambroziak, Agnieszka; Migdał, Marek; Szalecki, Mieczysław

2016-01-01

ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation) is characterized by rapid-onset obesity in young children, hypoventilation, and hypothalamic and autonomic dysfunction. The exact aetiology of the disease remains unknown, and the number of reported cases seems to be underestimated. We present the case of a nine-year-old male patient suspected of ROHHAD due to weight gain since early childhood, decreased height velocity, hypoventilation, hypodipsia, excessive perspiration, and pyrexial episodes. The presented symptoms, and laboratory and imaging findings met the criteria of ROHHAD syndrome. ROHHAD should be considered in differential diagnosis for obesity in children. Early identification of the disease prevents potential complications specific for the syndrome, in particular a life-threatening cardio-pulmonary arrest. Patients with ROHHAD require regular follow-up by a multidisciplinary team.

Autonomic hyper-reflexia modulated by percutaneous epidural neurostimulation: a preliminary report.

PubMed

Richardson, R R; Cerullo, L J; Meyer, P R

1979-06-01

Our clinical experience in the management of five paraplegic or quadriplegic patients with subjective complaints and objective findings of autonomic hyper-reflexia is presented. These five patients had epidural neurostimulation systems implanted percutaneously to regulate intractable spasticity. During a follow-up period varying from 2 months to almost 2 years, four of the five patients experienced no episodes of autonomic dysfunction with the use of a low frequency, low voltage, square wave pulse output. From their responses and from recent neurophysiological evidence, the potential benefit of percutaneous epidural neurostimulation in the modulation of autonomic hyper-reflexia without antihypertensive medication is suggested. Further follow-up of these patients and additional clinical research should be performed to confirm our initial clinical impressions.

Does stress induce bowel dysfunction?

PubMed

Chang, Yu-Ming; El-Zaatari, Mohamad; Kao, John Y

2014-08-01

Psychological stress is known to induce somatic symptoms. Classically, many gut physiological responses to stress are mediated by the hypothalamus-pituitary-adrenal axis. There is, however, a growing body of evidence of stress-induced corticotrophin-releasing factor (CRF) release causing bowel dysfunction through multiple pathways, either through the HPA axis, the autonomic nervous systems, or directly on the bowel itself. In addition, recent findings of CRF influencing the composition of gut microbiota lend support for the use of probiotics, antibiotics, and other microbiota-altering agents as potential therapeutic measures in stress-induced bowel dysfunction.

Dysfunctional brain-bone marrow communication: a paradigm shift in the pathophysiology of hypertension.

PubMed

Santisteban, Monica M; Zubcevic, Jasenka; Baekey, David M; Raizada, Mohan K

2013-08-01

It is widely accepted that the pathophysiology of hypertension involves autonomic nervous system dysfunction, as well as a multitude of immune responses. However, the close interplay of these systems in the development and establishment of high blood pressure and its associated pathophysiology remains elusive and is the subject of extensive investigation. It has been proposed that an imbalance of the neuro-immune systems is a result of an enhancement of the "proinflammatory sympathetic" arm in conjunction with dampening of the "anti-inflammatory parasympathetic" arm of the autonomic nervous system. In addition to the neuronal modulation of the immune system, it is proposed that key inflammatory responses are relayed back to the central nervous system and alter the neuronal communication to the periphery. The overall objective of this review is to critically discuss recent advances in the understanding of autonomic immune modulation, and propose a unifying hypothesis underlying the mechanisms leading to the development and maintenance of hypertension, with particular emphasis on the bone marrow, as it is a crucial meeting point for neural, immune, and vascular networks.

Dysfunctional brain-bone marrow communication: A paradigm shift in the pathophysiology of hypertension

PubMed Central

Santisteban, Monica M.; Zubcevic, Jasenka; Baekey, David M.; Raizada, Mohan K.

2013-01-01

It is widely accepted that the pathophysiology of hypertension involves autonomic nervous system dysfunction, as well as a multitude of immune responses. However, the close interplay of these systems in the development and establishment of high blood pressure and its associated pathophysiology remains elusive and is the subject of extensive investigation. It has been proposed that an imbalance of the neuro-immune systems is a result of an enhancement of the “pro-inflammatory sympathetic” arm in conjunction with dampening of the “anti-inflammatory parasympathetic” arm of the autonomic nervous system. In addition to the neuronal modulation of the immune system, it is proposed that key inflammatory responses are relayed back to the central nervous system and alter the neuronal communication to the periphery. The overall objective of this review is to critically discuss recent advances in the understanding of autonomic immune modulation, and propose a unifying hypothesis underlying the mechanisms leading to the development and maintenance of hypertension, with particular emphasis on the bone marrow, as it is a crucial meeting point for neural, immune, and vascular networks. PMID:23715920

The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy.

PubMed

Favoni, Valentina; Liguori, Rocco; Incensi, Alex; Fileccia, Enrico; Donadio, Vincenzo

2018-05-15

Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Dysautonomia (Autonomic Dysfunction)

MedlinePlus

... the head of the bed, water bolus (rapid infusion of water given intravenously), a high-salt diet, ... the head of the bed, water bolus (rapid infusion of water given intravenously), a high-salt diet, ...

Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia

PubMed Central

Laird, A S; Carrive, P; Waite, P M E

2006-01-01

In patients with high spinal cord injuries autonomic dysfunction can be dangerous, leading to medical complications such as postural hypotension, autonomic dysreflexia and temperature disturbance. While animal models have been developed to study autonomic dysreflexia, associated temperature changes have not been documented. Our aim here was to use radiotelemetry and infrared thermography in rodents to record the development of cardiovascular and skin temperature changes following complete T4 transection. In adult male Wistar rats (n = 5), responses were assessed prior to spinal cord injury (intact) and for 6 weeks following injury. Statistical analysis by a repeated-measure ANOVA revealed that following spinal cord injury (SCI), rats exhibited decreased mean arterial pressure (MAP, average decrease of 26 mmHg; P < 0.035) and elevated heart rate (HR, average increase of 65 bpm, P < 0.035) at rest. The basal core body temperature following SCI was also significantly lower than intact levels (−0.9°C; P < 0.0035). Associated with this decreased basal core temperature following SCI was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0°C, respectively; P < 0.0003) consistent with decreased cutaneous vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal distension (25 mmHg), was fully developed by 4 weeks after spinal cord transection, producing increases in MAP greater than 25 mmHg (P < 0.0003). In contrast to the tachycardia seen in intact animals in response to colorectal distension, SCI animals exhibited bradycardia (P < 0.0023). During episodes of autonomic dysreflexia mid-tail surface temperature decreased (approx. −1.7°C, P < 0.012), consistent with cutaneous vasoconstriction. This is the first study to compare cardiovascular dysfunction with temperature changes following spinal cord transection in rats. PMID:16973703

Heart rate variability measure in breast cancer patients and survivors: A systematic review.

PubMed

Arab, Claudia; Dias, Daniel Penteado Martins; Barbosa, Renata Thaís de Almeida; Carvalho, Tatiana Dias de; Valenti, Vitor Engrácia; Crocetta, Tânia Brusque; Ferreira, Marcelo; Abreu, Luiz Carlos de; Ferreira, Celso

2016-06-01

In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

PubMed

Chorepsima, Stamatina; Eleftheriadou, Ioanna; Tentolouris, Anastasios; Moyssakis, Ioannis; Protogerou, Athanasios; Kokkinos, Alexandros; Sfikakis, Petros P; Tentolouris, Nikolaos

2017-05-19

Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

Anaesthesia in the Guillian-Barré syndrome. A case report and recommendations.

PubMed

Perel, A; Reches, A; Davidson, J T

1977-03-01

A large proportion of patients with the Guillain Barré syndrome show signs of involvement of the autonomic nervous system beside the better known motor and sensory features of this disease. These patients present a substantial anaesthetic risk because of autonomic dysfunction. We present here an illustrative case in which the administration of a low subarachnoid block resulted in cardiac arrest and offer suggestions for the anaesthetic management of such cases.

Autonomic status and pain profile in patients of chronic low back pain and following electro acupuncture therapy: a randomized control trial.

PubMed

Shankar, Nilima; Thakur, Manisha; Tandon, Om Prakash; Saxena, Ashok Kumar; Arora, Shobha; Bhattacharya, Neena

2011-01-01

Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system. Chronic low back pain (LBP) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture. This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy. Chronic LBP patients (n=60) were recruited from the Department of Orthopaedics, GTB Hospital, Delhi. Age and sex matched healthy volunteers were selected as controls (n=30). Following a written consent, LBP patients were randomly allocated into two study groups - Group A received 10 sittings of electro acupuncture, on alternate days, at GB and UB points selected for back pain, while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy. Controls were assessed once while the patients were assessed twice, before and after completion of the treatment program (3 weeks). The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E: I ratio, 30:15 ratio, postural challenge test and sustained handgrip test. Pain intensity was measured with the visual analogue scale (VAS) and the global perceived effect (GPE). Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls (P<0.05 to P<0.001 in different variables). Following treatment, both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity. There was also a considerable relief of pain in both groups, however, the acupuncture group showed a better response (P<0.01). We conclude that there is autonomic dysfunction in chronic LBP patients. Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases.

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review.

PubMed

Ibáñez-Micó, S; Marcos Oltra, A M; de Murcia Lemauviel, S; Ruiz Pruneda, R; Martínez Ferrández, C; Domingo Jiménez, R

ROHHAD syndrome (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) is a rare and complex disease, presenting in previously healthy children at the age of 2-4 years. Up to 40% of cases are associated with neural crest tumours. We present the case of a 2-year-old girl with symptoms of rapidly progressing obesity, who a few months later developed hypothalamic dysfunction with severe electrolyte imbalance, behaviour disorder, hypoventilation, and severe autonomic dysregulation, among other symptoms. Although the pathophysiology of this syndrome remains unclear, an autoimmune hypothesis has been proposed for ROHHAD. Therefore, after obtaining a limited response to intravenous immunoglobulins, we decided to test the response to a high dose cyclophosphamide (low dose was not effective either). Unfortunately our patient experienced many severe complications (among them central pontine myelinolysis, from which the patient recovered, and failure to wean from the ventilator requiring tracheostomy and long term ventilation) that required a prolonged ICU stay. Although her behaviour improved, our patient unfortunately died suddenly at home at the age of 5 due to respiratory pathology. ROHHAD syndrome is a rare and little-known disease which requires a multidisciplinary approach because it involves complex symptoms and multiple organ system involvement. Alveolar hypoventilation should be identified early and appropriate treatment should be started promptly for the best possible outcome. Immunomodulatory treatment with immunoglobulins, cyclophosphamide, or rituximab has previously resulted in symptom improvement in some cases. Because of the low incidence of the syndrome, multi-centre studies must be carried out in order to gather more accurate information about ROHHAD pathophysiology and design an appropriate therapeutic approach. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of Prediction Model for Cardiovascular Autonomic Dysfunction Using Artificial Neural Network and Logistic Regression Analysis

PubMed Central

Zeng, Fangfang; Li, Zhongtao; Yu, Xiaoling; Zhou, Linuo

2013-01-01

Background This study aimed to develop the artificial neural network (ANN) and multivariable logistic regression (LR) analyses for prediction modeling of cardiovascular autonomic (CA) dysfunction in the general population, and compare the prediction models using the two approaches. Methods and Materials We analyzed a previous dataset based on a Chinese population sample consisting of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN and LR analysis, and were tested in the validation set. Performances of these prediction models were then compared. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with the prevalence of CA dysfunction (P<0.05). The mean area under the receiver-operating curve was 0.758 (95% CI 0.724–0.793) for LR and 0.762 (95% CI 0.732–0.793) for ANN analysis, but noninferiority result was found (P<0.001). The similar results were found in comparisons of sensitivity, specificity, and predictive values in the prediction models between the LR and ANN analyses. Conclusion The prediction models for CA dysfunction were developed using ANN and LR. ANN and LR are two effective tools for developing prediction models based on our dataset. PMID:23940593

LncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG.

PubMed

Wu, Bing; Zhang, Chunping; Zou, Lifang; Ma, Yucheng; Huang, Kangyu; Lv, Qiulan; Zhang, Xi; Wang, Shouyu; Xue, Yun; Yi, Zhihua; Jia, Tianyu; Zhao, Shanhong; Liu, Shuangmei; Xu, Hong; Li, Guilin; Liang, Shangdong

2016-05-01

Diabetic autonomic neuropathy includes the sympathetic ganglionic dysfunction. P2X7 receptor in superior cervical ganglia (SCG) participated in the pathological changes of cardiac dysfunction. Abnormal expression of long noncoding RNAs (lncRNAs) was reported to be involved in nervous system diseases. Our preliminary results obtained from rat lncRNA array profiling revealed that the expression of the uc.48+ was significantly increased in the rat SCG in response to diabetic sympathetic pathology. In this study, we found that lncRNAuc.48+ and P2X7 receptor in the SCG were increased in type 2 diabetic rats and were associated with the cardiac dysfunction. The uc.48+ small interference RNA (siRNA) improved the cardiac autonomic dysfunction and decreased the up-regulation P2X7 and the ratio of phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2) to ERK1/2 in SCG of type 2 diabetic rats. In conclusion, lncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats through regulating the expression of P2X7 and ERK signaling in SCG. Copyright © 2016 Elsevier B.V. All rights reserved.

Predicting athletes' functional and dysfunctional emotions: The role of the motivational climate and motivation regulations.

PubMed

Ruiz, Montse C; Haapanen, Saara; Tolvanen, Asko; Robazza, Claudio; Duda, Joan L

2017-08-01

This study examined the relationships between perceptions of the motivational climate, motivation regulations, and the intensity and functionality levels of athletes' pleasant and unpleasant emotional states. Specifically, we examined the hypothesised mediational role of motivation regulations in the climate-emotion relationship. We also tested a sequence in which emotions were assumed to be predicted by the motivational climate dimensions and then served as antecedents to variability in motivation regulations. Participants (N = 494) completed a multi-section questionnaire assessing targeted variables. Structural equation modelling (SEM) revealed that a perceived task-involving climate was a positive predictor of autonomous motivation and of the impact of functional anger, and a negative predictor of the intensity of anxiety and dysfunctional anger. Autonomous motivation was a partial mediator of perceptions of a task-involving climate and the impact of functional anger. An ego-involving climate was a positive predictor of controlled motivation, and of the intensity and impact of functional anger and the intensity of dysfunctional anger. Controlled motivation partially mediated the relationship between an ego-involving climate and the intensity of dysfunctional anger. Good fit to the data also emerged for the motivational climate, emotional states, and motivation regulations sequence. Findings provide support for the consideration of hedonic tone and functionality distinctions in the assessment of athletes' emotional states.

Incidental Transient Cortical Blindness after Lung Resection.

PubMed

Oncel, Murat; Sunam, Guven Sadi; Varoglu, Asuman Orhan; Karabagli, Hakan; Yildiran, Huseyin

2016-03-01

Transient vision loss after major surgical procedures is a rare clinical complication. The most common etiologies are cardiac, spinal, head, and neck surgeries. There has been no report on vision loss after lung resection. A 65-year-old man was admitted to our clinic with lung cancer. Resection was performed using right upper lobectomy with no complications. Cortical blindness developed 12 hours later in the postoperative period. Results from magnetic resonance imaging and diffusion-weighted investigations were normal. The neurologic examination was normal. The blood glucose level was 92 mg/dL and blood gas analysis showed a PO 2 of 82 mm Hg. After 24 hours, the patient began to see and could count fingers, and his vision was fully restored within 72 hours after this point. Autonomic dysfunction due to impaired microvascular structures in diabetes mellitus may induce posterior circulation dysfunction, even when the hemodynamic state is normal in the perioperative period. The physician must keep in mind that vision loss may occur after lung resection due to autonomic dysfunction, especially in older patients with diabetes mellitus.

The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms

NASA Technical Reports Server (NTRS)

Suarez, G. A.; Opfer-Gehrking, T. L.; Offord, K. P.; Atkinson, E. J.; O'Brien, P. C.; Low, P. A.

1999-01-01

OBJECTIVE: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. BACKGROUND: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. METHODS: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. RESULTS: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. CONCLUSIONS: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

Autonomic and metabolic effects of OSA in childhood obesity.

PubMed

Oliveira, F M; Tran, W H; Lesser, D; Bhatia, R; Ortega, R; Mittelman, S D; Keens, T G; Davidson Ward, S L; Khoo, M C

2010-01-01

This study investigates the effects of exposure to intermittent hypoxia on cardiovascular autonomic control and metabolic function in obese children with obstructive sleep apnea (OSA). Each subject underwent: (1) a polysomnography; (2) morning fasting blood samples and a subsequent FSIVGTT; (3) noninvasive measurement of respiration, arterial blood pressure, and heart rate during supine and standing postures. Assessment of adiposity was performed using a DEXA scan. From these measurements, we deduced the pertinent sleep parameters, Bergman minimal model parameters and the parameters characterizing a minimal model of cardiovascular variability. Results suggest that intermittent hypoxia in OSA contributes independently to insulin resistance and autonomic dysfunction in overweight children.

Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study

PubMed Central

Koopman, F.A.; Tang, M.W.; Vermeij, J.; de Hair, M.J.; Choi, I.Y.; Vervoordeldonk, M.J.; Gerlag, D.M.; Karemaker, J.M.; Tak, P.P.

2016-01-01

Background Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. Methods First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n = 20), individuals at risk of developing arthritis (AR subjects, n = 50) and RA patients (RA, n = 20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n = 45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. Findings Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68–73) and RA patients (68 bpm, IQR 62–76) had a significantly higher RHR compared to HS (60 bpm, IQR 56–63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥ 70 bpm compared to those with RHR < 70 bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. Interpretation These data support the notion that autonomic dysfunction precedes the development of RA. PMID:27211565

Short-term ECG recording for the identification of cardiac autonomic neuropathy in people with diabetes mellitus

NASA Astrophysics Data System (ADS)

Jelinek, Herbert F.; Pham, Phuong; Struzik, Zbigniew R.; Spence, Ian

2007-07-01

Diabetes mellitus (DM) is a serious and increasing health problem worldwide. Compared to non-diabetics, patients experience an increased risk of all cardiovascular diseases, including dysfunctional neural control of the heart. Poor diagnoses of cardiac autonomic neuropathy (CAN) may result in increased incidence of silent myocardial infarction and ischaemia, which can lead to sudden death. Traditionally the Ewing battery of tests is used to identify CAN. The purpose of this study is to examine the usefulness of heart rate variability (HRV) analyses of short-term ECG recordings as a method for detecting CAN. HRV may be able to identify asymptomatic individuals, which the Ewing battery is not able to do. Several HRV parameters are assessed, including time and frequency domain, as well as nonlinear parameters. Eighteen out of thirty-eight individuals with diabetes were positive for two or more of the Ewing battery of tests indicating CAN. Approximate Entropy (ApEn), log normalized total power (LnTP) and log normalized high frequency (LnHF) power demonstrate a significant difference at p < 0.05 between CAN+ and CAN-. This indicates that nonlinear scaling parameters are able to identify people with cardiac autonomic neuropathy in short ECG recordings. Our study paves the way to assess the utility of nonlinear parameters in identifying asymptomatic CAN.

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

PubMed Central

Ryu, Dong-Woo; Oh, Ju-Hee; Lee, Yang-Hyun; Park, Sung-Jin; Jeon, Kipyung; Lee, Jong-Yun; Ho, Seong Hee; So, Jungmin; Im, Jin Hee; Lee, Kwang-Soo

2017-01-01

Background and Purpose Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. Methods This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. Results Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. Conclusions The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug. PMID:27730767

RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

PubMed

Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

2015-02-01

Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction.

PubMed

Rodrigues, Bruno; Jorge, Luciana; Mostarda, Cristiano T; Rosa, Kaleizu T; Medeiros, Alessandra; Malfitano, Christiane; de Souza, Alcione L; Viegas, Katia Aparecida da Silva; Lacchini, Silvia; Curi, Rui; Brum, Patricia C; De Angelis, Kátia; Irigoyen, Maria Cláudia

2012-09-01

Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. Copyright © 2012 Elsevier Inc. All rights reserved.

BIOMARKERS for CHRONIC FATIGUE

PubMed Central

Broderick, Gordon; Fletcher, Mary Ann

2012-01-01

Fatigue that persists for 6 months or more is termed chronic fatigue. Chronic fatigue (CF) in combination with a minimum of 4 of 8 symptoms and the absence of diseases that could explain these symptoms, constitute the case definition for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Inflammation, immune system activation, autonomic dysfunction, impaired functioning in the hypothalamic-pituitary-adrenal axis, and neuroendocrine dysregulation have all been suggested as root causes of fatigue. The identification of objective markers consistently associated with CFS/ME is an important goal in relation to diagnosis and treatment, as the current case definitions are based entirely on physical signs and symptoms. This review is focused on the recent literature related to biomarkers for fatigue associated with CFS/ME and, for comparison, those associated with other diseases. These markers are distributed across several of the body’s core regulatory systems. A complex construct of symptoms emerges from alterations and/or dysfunctions in the nervous, endocrine and immune systems. We propose that new insight will depend on our ability to develop and deploy an integrative profiling of CFS/ME pathogenesis at the molecular level. Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited. PMID:22732129

Animal models of the non-motor features of Parkinson’s disease

PubMed Central

McDowell, Kimberly; Chesselet, Marie-Françoise

2012-01-01

The non-motor symptoms (NMS) of Parkinson’s disease (PD) occur in roughly 90% of patients, have a profound negative impact on their quality of life, and often go undiagnosed. NMS typically involve many functional systems, and include sleep disturbances, neuropsychiatric and cognitive deficits, and autonomic and sensory dysfunction. The development and use of animal models have provided valuable insight into the classical motor symptoms of PD over the past few decades. Toxin-induced models provide a suitable approach to study aspects of the disease that derive from the loss of nigrostriatal dopaminergic neurons, a cardinal feature of PD. This also includes some NMS, primarily cognitive dysfunction. However, several NMS poorly respond to dopaminergic treatments, suggesting that they may be due to other pathologies. Recently developed genetic models of PD are providing new ways to model these NMS and identify their mechanisms. This review summarizes the current available literature on the ability of both toxin-induced and genetically-based animal models to reproduce the NMS of PD. PMID:22236386

Lower limb and back pain in Guillain-Barré syndrome and associated contrast enhancement in MRI of the cauda equina.

PubMed

Wilmshurst, J M; Thomas, N H; Robinson, R O; Bingham, J B; Pohl, K R

2001-06-01

This study assesses the frequency of lower limb and back pain in children with Guillain-Barré syndrome and reviews the magnetic resonance imaging results of those undergoing spinal imaging. Over an 8-y period, nine children presented with various combinations of severe back pain, leg pains, impairment of gait and bladder dysfunction. Guillain-Barré syndrome was confirmed on clinical examination and peripheral electrophysiology (n = 8). Magnetic resonance imaging in four patients, following contrast injection, showed enhancement of the cauda equine and, additionally, of the cervical nerve roots in one of the patients. A further patient, who was not scanned with contrast, had abnormal thickening of the lumbar roots. Carbamazepine and steroids were effectively used for analgesia in three cases. All the patients recovered. Guillain-Barré syndrome should be considered in the differential diagnosis of children presenting with back and/or leg pain. Early diagnosis ensures prompt monitoring for autonomic dysfunction and respiratory compromise.

Distinct Clinical Characteristics of Pediatric Guillain-Barré Syndrome: A Comparative Study between Children and Adults in Northeast China

PubMed Central

Wu, Xiujuan; Shen, Donghui; Li, Ting; Zhang, Bing; Li, Chunrong; Mao, Mei; Zhao, Jixue; Liu, Kangding; Zhang, Hong-Liang

2016-01-01

Objective Clinical characteristics of pediatric Guillain-Barré syndrome (GBS) have been extensively studied whereas scarcely been compared with those of adult GBS. Herein we compared the clinical features of GBS between pediatric and adult patients. Methods We retrospectively collected the clinical data of 750 patients with GBS (541 adults and 209 children), and compared the clinical characteristics between children and adults. Results Pain was a more frequent complaint in children (17.2% vs 9.6%, p < 0.01), who were also found with shorter interval from disease onset to nadir (6.3d vs 7.3d, p < 0.01) and higher incidence of bulbar dysfunction (22.0% vs 14.8%, p < 0.05). The disease severity in children was comparable with adults. In addition, a higher incidence of pediatric GBS was found in summer, especially in July and August (both p < 0.01). However, the incidence of antecedent infections of different seasons in adult and pediatric patients was comparable (p > 0.05). The clinical features of acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) in children were overall comparable with adult ones (p > 0.05). Similar to adults, bulbar dysfunction (odds ratio [OR]: 4.621, 95% confidence interval [CI]: 1.240–17.218, p < 0.05) and lower nadir Medical Research Council (MRC) sum score (OR: 0.897, 95% CI: 0.855–0.941, p < 0.01) were also risk factors for mechanical ventilation in children. However, distinct from adult ones, autonomic dysfunction was significantly higher in mechanically ventilated childhood GBS (39.1% vs 8.8%, p < 0.01), which also served as a predictor for mechanical ventilation in pediatric GBS (OR: 70.415, 95% CI: 9.265–535.158, p < 0.01). As to the efficacy of intravenous immunoglobulin, insignificant difference was identified between children and adults. Conclusion The clinical features of pediatric GBS differ from those of adults. Autonomic dysfunction is an independent risk factor for mechanical ventilation in pediatric patients. PMID:26974666

Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome.

PubMed

Bär, Karl-Jürgen; Boettger, Michael Karl; Neubauer, Rene; Grotelüschen, Marei; Jochum, Thomas; Baier, Vico; Sauer, Heinrich; Voss, Andreas

2006-09-01

Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n = 20, no treatment required) and in patients with moderate to severe AW syndrome (n = 20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies.

Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Robertson, R. M.; Robertson, D.

1994-01-01

It has been postulated that alpha 2-adrenergic receptors play a modulatory role in the regulation of blood pressure. Activation of alpha 2-receptors located in the central nervous system results in inhibition of sympathetic tone and decrease of blood pressure. This indeed may be the mechanism of action of central sympatholytic antihypertensives such as alpha-methyldopa. Presynaptic alpha 2-receptors also are found in adrenergic nerve terminals. These receptors act as a negative feedback mechanism by inhibiting the release of norepinephrine. The relevance of alpha 2-adrenergic receptors for blood pressure regulation can be explored with yohimbine, a selective antagonist of these receptors. Yohimbine increases blood pressure in resting normal volunteers. This effect is associated with an increase in both sympathetic nerve activity, reflecting an increase in central sympathetic outflow, and in norepinephrine spillover, reflecting potentiation of the release of norepinephrine from adrenergic nerve terminals. These actions, therefore, underscore the importance of alpha 2-adrenergic receptors for blood pressure regulation even under resting conditions. Patients with autonomic failure, even those with severe sympathetic deprivation, are hypersensitive to the pressor effects of yohimbine. This increased responsiveness can be explained by sensitization of adrenergic receptors, analogous to denervation supersensitivity, and by the lack of autonomic reflexes that would normally buffer any increase in blood pressure. Preliminary studies suggest that the effectiveness of yohimbine in autonomic failure can be enhanced with monoamine oxidase inhibitors. Used in combination, yohimbine increases norepinephrine release, whereas monoamine oxidase inhibitors inhibit its degradation. Therefore, yohimbine is not only a useful tool in the study of blood pressure regulation, but may offer a therapeutic option in autonomic dysfunction.

Abnormalities of the QT interval in primary disorders of autonomic failure

NASA Technical Reports Server (NTRS)

Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

1998-01-01

BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Twenty-Four Hour Non-Invasive Ambulatory Blood Pressure and Heart Rate Monitoring in Parkinson’s Disease

PubMed Central

Stuebner, Eva; Vichayanrat, Ekawat; Low, David A.; Mathias, Christopher J.; Isenmann, Stefan; Haensch, Carl-Albrecht

2013-01-01

Non-motor symptoms are now commonly recognized in Parkinson’s disease (PD) and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-Parkinsonian) drugs and can result in atypical blood pressure (BP) readings and related symptoms such as orthostatic hypotension (OH) and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT) or an (active) standing test (also known as Schellong test) in the laboratory, but 24 h ambulatory blood pressure monitoring (ABPM) in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary) is followed which will be discussed in this review. A 24-h ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR) can be obtained and establish whether or not a patient has a fall of BP at night (i.e., “dipper” vs. non-“dipper”). The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders, and obstructive sleep apnea, which are common in PD. Additionally, a 24-h ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 h ABPM in PD, summarize findings of such studies in PD, and briefly consider common daily stimuli that might affect 24 h ABPM. PMID:23720648

Whole Exome Sequencing Identifies RAI1 Mutation in a Morbidly Obese Child Diagnosed With ROHHAD Syndrome

PubMed Central

Esteves, Kristyn M.; Towne, Meghan C.; Brownstein, Catherine A.; James, Philip M.; Crowley, Laura; Hirschhorn, Joel N.; Elsea, Sarah H.; Beggs, Alan H.; Picker, Jonathan

2015-01-01

Context: The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis. Objective: To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. Design/Setting/Intervention: The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing. Results: We identified a novel de novo nonsense mutation, c.3265 C>T (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutations in the RAI1 gene are known to cause Smith-Magenis syndrome (SMS). On further evaluation, his clinical features were not typical of either SMS or ROHHAD syndrome. Conclusions: This study identifies a de novo RAI1 mutation in a child with morbid obesity and a clinical diagnosis of ROHHAD syndrome. Although extreme early-onset obesity, autonomic disturbances, and hypoventilation are present in ROHHAD, several of the clinical findings are consistent with SMS. This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS. We also propose RAI1 as a candidate gene for children with morbid obesity. PMID:25781356

Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome.

PubMed

Thaker, Vidhu V; Esteves, Kristyn M; Towne, Meghan C; Brownstein, Catherine A; James, Philip M; Crowley, Laura; Hirschhorn, Joel N; Elsea, Sarah H; Beggs, Alan H; Picker, Jonathan; Agrawal, Pankaj B

2015-05-01

The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis. To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. Design/Setting/Intervention: The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing. We identified a novel de novo nonsense mutation, c.3265 C>T (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutations in the RAI1 gene are known to cause Smith-Magenis syndrome (SMS). On further evaluation, his clinical features were not typical of either SMS or ROHHAD syndrome. This study identifies a de novo RAI1 mutation in a child with morbid obesity and a clinical diagnosis of ROHHAD syndrome. Although extreme early-onset obesity, autonomic disturbances, and hypoventilation are present in ROHHAD, several of the clinical findings are consistent with SMS. This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS. We also propose RAI1 as a candidate gene for children with morbid obesity.

Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study.

PubMed

Halbach, Nicky; Smeets, Eric E; Julu, Peter; Witt-Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F; Borelli, Paolo; Candel, Math; Curfs, Leopold

2016-09-01

Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Heart rate turbulence.

PubMed

Cygankiewicz, Iwona

2013-01-01

Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. © 2013.

Adolescent Fatigue, POTS, and Recovery: A Guide for Clinicians

PubMed Central

Kizilbash, Sarah J.; Ahrens, Shelley P.; Bruce, Barbara K.; Chelimsky, Gisela; Driscoll, Sherilyn W.; Harbeck-Weber, Cynthia; Lloyd, Robin M.; Mack, Kenneth J.; Nelson, Dawn E.; Ninis, Nelly; Pianosi, Paolo T.; Stewart, Julian M.; Weiss, Karen E.; Fischer, Philip R.

2018-01-01

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive–behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary. PMID:24819031

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurhanewicz, Nicole

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once tomore » 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac effects. • Sensory irritation contributes to acrolein-induced cardiac arrhythmia & dysfunction.« less

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia.

PubMed

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia

PubMed Central

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

2016-01-01

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS. PMID:27725556

PubMed Central

St-Laurent, J.; Gastaut, H.; Lanoir, J.; Naquet, R.

1966-01-01

One hundred patients with slow rhythmical electro-encephalographic (EEG) activity in the posterior regions were classified according to their clinical symptomatology. Correlations were established between the occurrence of the slow posterior rhythm (SPR) and head injury, and psychological, autonomic or vascular disturbances. In contrast to most previous publications, the patients with head injury constituted only one-half of the series. Autonomic and psychological complaints were frequently encountered in this group. A second group of 11 patients had some type of vascular pathology. A third group of 39 patients had symptoms of anxiety and autonomic system disturbance. The importance of head injury as a factor responsible for SPR seems to have been overrated. Regardless of classification, psychological symptoms were found in 50% and autonomic dysfunction in 53% of all patients. It is apparent that the origin and significance of slow posterior rhythm have not yet been eludicated. PMID:5940323

Validation of the Bulgarian version of Scales for Outcomes in Parkinson's Disease - Autonomic (SCOPA-AUT-BG).

PubMed

Mantarova, Stefka G; Velcheva, Irena V; Georgieva, Spaska O; Stambolieva, Katerina I

2013-01-01

The last twenty years have witnessed a surge of interest in the autonomic symptoms in Parkinson's disease (PD) and the possibilities to diagnose and treat them. The specialized questionnaire assessing the autonomic symptoms in Parkinson's disease (SCOPA-AUT) has been validated and available in English, Dutch and Spanish. In this study we aim at evaluating the validity, reliability and applicability of the Bulgarian version of SCOPA-AUT (SCOPA-AUT-BG). The study included 55 patients with idiopathic PD (mean age 64.4 +/- 8.9 yrs), and 40 healthy controls (mean age 58.5 +/- 9.4 yrs). Clinical severity and disease stage were assessed by United Parkinson's disease rating scale (UPRDS) and Hoen and Yahr (H&Y). Thirty-two of the PD patients completed SCOPA-AUT-BG again after a 7-day interval. Questionnaire reliability was analyzed by determining the internal consistency, homogeneity, discriminatory and construct validity and test-retest reliability. Analyses showed good internal consistency of the summary evaluation of SCOPA-AUT-BG (coefficient alpha of Cronbach = 0.79), which indicates the high reliability of the questionnaire. The lowest Cronbach's alpha coefficient (0.53) was found for the subscale "cardiovascular functions". A dominant role belongs to the subscales for gastrointestinal and urinary functions (Cronbach's Alpha > 0.7), where a significantly high correlation of PD with the UPDRS scale was observed. We found high test-retest reliability based on the responses associated with dysfunction of the gastrointestinal, urinary, thermoregulatory and pupillary autonomic systems. The correlation of the results of SCOPA-AUT-BG with UPDRS is higher than that with H&Y, and the construct validity is high except for the cardiovascular and pupillomotor functions subscales. The results of this study show that SCOPA-AUT-BG is a valid and reliable specialized questionnaire to evaluate autonomic function in patients with Parkinson's disease. Using it allows for more detailed clinical evaluation of these patients and justifies the need to refer them to specialized examination of autonomic functions.

Validation of the Korean Version of the Scale for Outcomes in Parkinson’s Disease-Autonomic

PubMed Central

Kim, Ji-Young; Song, In-Uk; Koh, Seong-Beom; Ahn, Tae-Beom; Kim, Sang Jin; Cheon, Sang-Myung; Cho, Jin Whan; Kim, Yun Joong; Ma, Hyeo-Il; Park, Mee-Young; Baik, Jong Sam; Lee, Phil Hyu; Chung, Sun Ju; Kim, Jong-Min; Kim, Han-Joon; Sung, Young-Hee; Kwon, Do Young; Lee, Jae-Hyeok; Lee, Jee-Young; Kim, Ji Sun; Yun, Ji Young; Kim, Hee Jin; Hong, Jin Young; Kim, Mi-Jung; Youn, Jinyoung; Kim, Ji Seon; Oh, Eung Seok; Yang, Hui-Jun; Yoon, Won Tae; You, Sooyeoun; Kwon, Kyum-Yil; Park, Hyung-Eun; Lee, Su-Yun; Kim, Younsoo; Kim, Hee-Tae; Kim, Joong-Seok

2017-01-01

Objective Autonomic symptoms are commonly observed in patients with Parkinson’s disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson’s disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients. Methods For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10−14 days. Results The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach’s α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson’s Disease Rating Scale part II) and quality of life [the Korean version of Parkinson’s Disease Quality of Life 39 (K-PDQ39)]. Conclusion The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life. PMID:28122431

Astrocytes influence the severity of spinal muscular atrophy

PubMed Central

Rindt, Hansjörg; Feng, Zhihua; Mazzasette, Chiara; Glascock, Jacqueline J.; Valdivia, David; Pyles, Noah; Crawford, Thomas O.; Swoboda, Kathryn J.; Patitucci, Teresa N.; Ebert, Allison D.; Sumner, Charlotte J.; Ko, Chien-Ping; Lorson, Christian L.

2015-01-01

Systemically low levels of survival motor neuron-1 (SMN1) protein cause spinal muscular atrophy (SMA). α-Motor neurons of the spinal cord are considered particularly vulnerable in this genetic disorder and their dysfunction and loss cause progressive muscle weakness, paralysis and eventually premature death of afflicted individuals. Historically, SMA was therefore considered a motor neuron-autonomous disease. However, depletion of SMN in motor neurons of normal mice elicited only a very mild phenotype. Conversely, restoration of SMN to motor neurons in an SMA mouse model had only modest effects on the SMA phenotype and survival. Collectively, these results suggested that additional cell types contribute to the pathogenesis of SMA, and understanding the non-autonomous requirements is crucial for developing effective therapies. Astrocytes are critical for regulating synapse formation and function as well as metabolic support for neurons. We hypothesized that astrocyte functions are disrupted in SMA, exacerbating disease progression. Using viral-based restoration of SMN specifically to astrocytes, survival in severe and intermediate SMA mice was observed. In addition, neuromuscular circuitry was improved. Astrogliosis was prominent in end-stage SMA mice and in post-mortem patient spinal cords. Increased expression of proinflammatory cytokines was partially normalized in treated mice, suggesting that astrocytes contribute to the pathogenesis of SMA. PMID:25911676

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): Response to ventilatory challenges.

PubMed

Carroll, Michael S; Patwari, Pallavi P; Kenny, Anna S; Brogadir, Cindy D; Stewart, Tracey M; Weese-Mayer, Debra E

2015-12-01

Hypoventilation is a defining feature of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), a rare respiratory and autonomic disorder. This chronic hypoventilation has been explained as the result of dysfunctional chemosensory control circuits, possibly affecting peripheral afferent input, central integration, or efferent motor control. However, chemosensory function has never been quantified in a cohort of ROHHAD patients. Therefore, the purpose of this study was to assess the response to awake ventilatory challenge testing in children and adolescents with ROHHAD. The ventilatory, cardiovascular and cerebrovascular responses in 25 distinct comprehensive physiological recordings from seven unique ROHHAD patients to three different gas mixtures were analyzed at breath-to-breath and beat-to-beat resolution as absolute measures, as change from baseline, or with derived metrics. Physiologic measures were recorded during a 3-min baseline period of room air, a 3-min gas exposure (of 100% O2; 95% O2, 5% CO2; or 14% O2, 7% CO2 balanced with N2), and a 3-min recovery period. An additional hypoxic challenge was conducted which consisted of either five or seven tidal breaths of 100% N2. While ROHHAD cases showed a diminished VT and inspiratory drive response to hypoxic hypercapnia and absent behavioral awareness of the physiologic compromise, most ventilatory, cardiovascular, and cerebrovascular measures were similar to those of previously published controls using an identical protocol, suggesting a mild chemosensory deficit. Nonetheless, the high mortality rate, comorbidity and physiological fragility of patients with ROHHAD demand continued clinical vigilance. © 2015 Wiley Periodicals, Inc.

Psychobiology of depression/distress in congestive heart failure

PubMed Central

Hassan, Mustafa; Sheps, David S.

2011-01-01

Heart failure affects millions of Americans and new diagnosis rates are expected to almost triple over the next 30 years as our population ages. Affective disorders including clinical depression and anxiety are common in patients with congestive heart failure. Furthermore, the presence of these disorders significantly impacts quality of life, medical outcomes, and healthcare service utilization. In recent years, the literature has attempted to describe potential pathophysiologic mechanisms relating affective disorders and psychosocial stress to heart failure. Several potential mechanisms have been proposed including autonomic nervous system dysfunction, inflammation, cardiac arrhythmias, and altered platelet function. These mechanisms are reviewed in this article. Additional novel mechanisms such as mental stress-induced myocardial ischemia are also discussed. PMID:18368481

Cell therapy for spinal cord injury informed by electromagnetic waves.

PubMed

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

[Time-organization of EEG patterns' structure in anxiety and phobic disorders].

PubMed

Sviatogor, I A; Mokhovikova, I A

2005-01-01

Thirty-five patients, aged 19-48 years (mean age 38 years) with anxiety and phobic disorders were examined. According to ICD-10 criteria--social phobia (F40.1), panic disorder (F41.0), somatoform autonomic dysfunction (F45.3) were diagnosed. Using electroencephalography data, qualitative and quantitative characteristics of the time- and spatial-organization of brain EEG activity in anxiety and phobic disorders of different severity were established. It were determined 4 types of wave interactions between EEG components, which reflected a different extent of the regulatory mechanisms lesions: 2 structures with one core component (alpha or beta), a structure with two core components and a non-organized structure.

Postural instability and gait are associated with severity and prognosis of Parkinson disease.

PubMed

van der Heeden, Jorine F; Marinus, Johan; Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Geraedts, Victor J; van Hilten, Jacobus J

2016-06-14

Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications. Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365). The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results. In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself. © 2016 American Academy of Neurology.

Cardiovascular autonomic control in paraplegic and quadriplegic.

PubMed

de Carvalho Abreu, Elizângela Márcia; Dias, Lucas Pinto Salles; Lima, Fernanda Pupio Silva; de Paula Júnior, Alderico Rodrigues; Lima, Mário Oliveira

2016-04-01

Spinal cord injury (SCI) is commonly associated with devastating paralysis. This condition also results in cardiovascular autonomic dysfunction associated with increased mortality from cardiovascular disease. The purpose of this study was to explore the differences in cardiovascular autonomic modulation in individuals with and without SCI. The study included 60 individuals: 30 individuals without SCI, who formed the control group-CG and 30 individuals with SCI, who formed the SCI group-SCIG. The latter group was divided into two, one group of subjects with SCI above the spinal segment T6-SCIG (above T6) and a group of individuals with SCI below T6-SCIG (below T6). The subjects were evaluated by linear and nonlinear analysis of heart rate variability (HRV). The SCIG showed significantly lower square root of the mean squares differences of successive NN intervals (rMSSD), number of pairs of adjacent NN intervals differing by more than 50 ms (pNN50), standard deviation of short-term HRV (SD1), and high frequency power (HF). Their low frequency power (LF) in absolute units (ms(2)) was significantly lower and their normalized units (n.u.) were significantly higher. Their LF/HF ratio was significantly higher, and sample entropy (SampEn), which indicates the complexity and irregularity of the NN intervals time series, was significantly lower compared to the CG. The differences between the SCIG and CG were derived mainly from the SCIG (above T6). The correlation test revealed very low values between each of the parameters evaluated for CG and SCIG. The SCIG (above T6) showed greater cardiovascular autonomic impairment compared to SCIG (below T6) and CG. The SCIG (below T6) also presented some degree of autonomic dysfunction. All parameters, linear or nonlinear, are suitable to demonstrate the differences between the SCIG and CG.

An epigenome-wide association analysis of cardiac autonomic responses among a population of welders.

PubMed

Zhang, Jinming; Liu, Zhonghua; Umukoro, Peter E; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc G; Lin, Xihong; Mittleman, Murray A; Christiani, David C

2017-02-01

DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.

Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in multiple sclerosis.

PubMed

Nomura, Shohei; Shimakawa, Shuichi; Kashiwagi, Mitsuru; Tanabe, Takuya; Fukui, Miho; Tamai, Hiroshi

2015-11-01

Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

May diabetes patients have trouble sleeping despite not having obesity?

PubMed

Rizzi, Maurizio; Razionale, Giancarlo; Bamberga, Michele; Barrella, Massimo; Kotzalidis, Georgios D; Certan, Diana; Bevilacqua, Maurizio

2014-06-01

Obstructive sleep apnea (OSA) and periodic limb movements during sleep (PLMs) are sleep-related disorders with a high prevalence in type 2 diabetes. Commonly OSA is considered as a consequence of obesity, but several previous studies have shown the presence of OSA in non-obese diabetic patients. A previous study showed higher PLMs prevalence in patients with type 2 diabetes, compared to age-matched controls. We speculated that both OSA and PLMs may reflect the presence of diabetic autonomic neuropathy. To test this hypothesis, we compared a group of 112 non-obese patients with type 2 diabetes with 66 age-, sex-, and body mass index- matched nondiabetic patients. Both groups have been investigated through a set of tests including the Epworth Sleepiness Scale, polysomnography, and the Orthostatic Grading Scale (OGS), a questionnaire to assess the degree of autonomic dysfunction. Diabetic patients with OSA and PLMs scored higher on the OGS than controls. Our results confirm that both OSA and PLMs are related to dysautonomy and may be unrelated to obesity in type 2 diabetes patients.

Cardiac Autonomic Dysfunction in Offspring of Hypertensive Parents During Exercise.

PubMed

Almeida, Leonardo Barbosa de; Peçanha, Tiago; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; da Silva, Lílian Pinto; Martinez, Daniel Godoy; Freitas, Isabelle Magalhães Guedes; Laterza, Mateus Camaroti

2017-12-01

Offspring of hypertensive parents present autonomic dysfunction at rest and during physiological maneuvers. However, the cardiac autonomic modulation during exercise remains unknown. This study tested whether the cardiac autonomic modulation would be reduced in offspring of hypertensive parents during exercise. Fourteen offspring of hypertensive and 14 offspring of normotensive individuals were evaluated. The groups were matched by age (24.5±1.0 vs. 26.6±1.5 years; p=0.25) and BMI (22.8±0.6 vs. 24.2±1.0 kg/m 2 ; p=0.30). Blood pressure and heart rate were assessed simultaneously during 3 min at baseline followed by 3-min isometric handgrip at 30% of maximal voluntary contraction. Cardiac autonomic modulation was evaluated using heart rate variability. Primary variables were subjected to two-way ANOVA (group vs. time). P value<0.05 was considered statistically significant. Blood pressure and heart rate were similar between groups during exercise protocol. In contrast, offspring of hypertensive subjects showed a reduction of SDNN (Basal=34.8±3.5 vs. 45.2±3.7 ms; Exercise=30.8±3.3 vs. 41.5±3.9 ms; p group=0.01), RMSSD (Basal=37.1±3.7 vs. 52.0±6.0 ms; Exercise=28.6±3.4 vs. 41.9±5.3 ms; p group=0.02) and pNN50 (Basal=15.7±4.0 vs. 29.5±5.5%; Exercise=7.7±2.4 vs. 18.0±4.3%; p group=0.03) during the exercise protocol in comparison with offspring of normotensive parents. We concluded that normotensive offspring of hypertensive parents exhibit impaired cardiac autonomic modulation during exercise. © Georg Thieme Verlag KG Stuttgart · New York.

The relationship between erythrocyte membrane fatty acid levels and cardiac autonomic function in obese children.

PubMed

Mustafa, Gulgun; Kursat, Fidanci Muzaffer; Ahmet, Tas; Alparslan, Genc Fatih; Omer, Gunes; Sertoglu, Erdem; Erkan, Sarı; Ediz, Yesilkaya; Turker, Turker; Ayhan, Kılıc

Childhood obesity is a worldwide health concern. Studies have shown autonomic dysfunction in obese children. The exact mechanism of this dysfunction is still unknown. The aim of this study was to assess the relationship between erythrocyte membrane fatty acid (EMFA) levels and cardiac autonomic function in obese children using heart rate variability (HRV). A total of 48 obese and 32 healthy children were included in this case-control study. Anthropometric and biochemical data, HRV indices, and EMFA levels in both groups were compared statistically. HRV parameters including standard deviation of normal-to-normal R-R intervals (NN), root mean square of successive differences, the number of pairs of successive NNs that differ by >50 ms (NN50), the proportion of NN50 divided by the total number of NNs, high-frequency power, and low-frequency power were lower in obese children compared to controls, implying parasympathetic impairment. Eicosapentaenoic acid and docosahexaenoic acid levels were lower in the obese group (p<0.001 and p=0.012, respectively). In correlation analysis, in the obese group, body mass index standard deviation and linoleic acid, arachidonic acid, triglycerides, and high-density lipoprotein levels showed a linear correlation with one or more HRV parameter, and age, eicosapentaenoic acid, and systolic and diastolic blood pressure correlated with mean heart rate. In linear regression analysis, age, dihomo-gamma-linolenic acid, linoleic acid, arachidonic acid, body mass index standard deviation, systolic blood pressure, triglycerides, low-density lipoprotein and high-density lipoprotein were related to HRV parameters, implying an effect on cardiac autonomic function. There is impairment of cardiac autonomic function in obese children. It appears that levels of EMFAs such as linoleic acid, arachidonic acid and dihomo-gamma-linolenic acid play a role in the regulation of cardiac autonomic function in obese children. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Sympathetic nerve dysfunction is common in patients with chronic intestinal pseudo-obstruction.

PubMed

Mattsson, Tomas; Roos, Robert; Sundkvist, Göran; Valind, Sven; Ohlsson, Bodil

2008-02-01

To clarify whether disturbances in the autonomic nervous system, reflected in abnormal cardiovascular reflexes, could explain symptoms of impaired heat regulation in patients with intestinal pseudo-obstruction. Chronic intestinal pseudo-obstruction is a clinical syndrome characterized by diffuse, unspecific gastrointestinal symptoms due to damage to the enteric nervous system or the smooth muscle cells. These patients often complain of excessive sweating or feeling cold, suggesting disturbances in the autonomic nervous system. Earlier studies have pointed to a coexistence of autonomic disturbances in the enteric and cardiovascular nervous system. Thirteen consecutive patients (age range 23 to 79, mean 44 y) fulfilling the criteria for chronic intestinal pseudo-obstruction were investigated. Six of them complained of sweating or a feeling of cold. Examination of autonomic reflexes included heart rate variation to deep-breathing (expiration/inspiration index), heart rate reaction to tilt (acceleration index, brake index), and vasoconstriction (VAC) due to indirect cooling by laser doppler (VAC-index; high index indicates impaired VAC). Test results in patients were compared with healthy individuals. Patients had significantly higher (more abnormal) median VAC-index compared with healthy controls [1.79 (interquartile ranges 1.89) vs. 0.08 (interquartile ranges 1.29); P=0.0007]. However, symptoms of impaired heat regulation were not related to the VAC-index. There were no differences in expiration/inspiration, acceleration index, or brake index between patients and controls. The patients with severe gastrointestinal dysmotility showed impaired sympathetic nerve function which, however, did not seem to be associated with symptoms of impaired heat regulation.

Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure.

PubMed

Ichige, Marcelo H A; Santos, Carla R; Jordão, Camila P; Ceroni, Alexandre; Negrão, Carlos E; Michelini, Lisete C

2016-11-01

Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure. Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults.

PubMed

Walker, Lynn S; Stone, Amanda L; Smith, Craig A; Bruehl, Stephen; Garber, Judy; Puzanovova, Martina; Diedrich, André

2017-08-01

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.

Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism

PubMed Central

Jeong, Mark Y.; Lin, Ying H.; Wennersten, Sara A.; Demos-Davies, Kimberly M.; Cavasin, Maria A.; Mahaffey, Jennifer H.; Monzani, Valmen; Saripalli, Chandrasekhar; Mascagni, Paolo; Reece, T. Brett; Ambardekar, Amrut V.; Granzier, Henk L.; Dinarello, Charles A.; McKinsey, Timothy A.

2018-01-01

There are no approved drugs for the treatment of heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular (LV) diastolic dysfunction. We demonstrate that ITF2357 (givinostat), a clinical-stage inhibitor of histone deacetylase (HDAC) catalytic activity, is efficacious in two distinct murine models of diastolic dysfunction with preserved EF. ITF2357 blocked LV diastolic dysfunction due to hypertension in Dahl salt-sensitive (DSS) rats and suppressed aging-induced diastolic dysfunction in normotensive mice. HDAC inhibitor–mediated efficacy was not due to lowering blood pressure or inhibiting cellular and molecular events commonly associated with diastolic dysfunction, including cardiac fibrosis, cardiac hypertrophy, or changes in cardiac titin and myosin isoform expression. Instead, ex vivo studies revealed impairment of cardiac myofibril relaxation as a previously unrecognized, myocyte-autonomous mechanism for diastolic dysfunction, which can be ameliorated by HDAC inhibition. Translating these findings to humans, cardiac myofibrils from patients with diastolic dysfunction and preserved EF also exhibited compromised relaxation. These data suggest that agents such as HDAC inhibitors, which potentiate cardiac myofibril relaxation, hold promise for the treatment of HFpEF in humans. PMID:29437146

Human-machine interfaces based on EMG and EEG applied to robotic systems.

PubMed

Ferreira, Andre; Celeste, Wanderley C; Cheein, Fernando A; Bastos-Filho, Teodiano F; Sarcinelli-Filho, Mario; Carelli, Ricardo

2008-03-26

Two different Human-Machine Interfaces (HMIs) were developed, both based on electro-biological signals. One is based on the EMG signal and the other is based on the EEG signal. Two major features of such interfaces are their relatively simple data acquisition and processing systems, which need just a few hardware and software resources, so that they are, computationally and financially speaking, low cost solutions. Both interfaces were applied to robotic systems, and their performances are analyzed here. The EMG-based HMI was tested in a mobile robot, while the EEG-based HMI was tested in a mobile robot and a robotic manipulator as well. Experiments using the EMG-based HMI were carried out by eight individuals, who were asked to accomplish ten eye blinks with each eye, in order to test the eye blink detection algorithm. An average rightness rate of about 95% reached by individuals with the ability to blink both eyes allowed to conclude that the system could be used to command devices. Experiments with EEG consisted of inviting 25 people (some of them had suffered cases of meningitis and epilepsy) to test the system. All of them managed to deal with the HMI in only one training session. Most of them learnt how to use such HMI in less than 15 minutes. The minimum and maximum training times observed were 3 and 50 minutes, respectively. Such works are the initial parts of a system to help people with neuromotor diseases, including those with severe dysfunctions. The next steps are to convert a commercial wheelchair in an autonomous mobile vehicle; to implement the HMI onboard the autonomous wheelchair thus obtained to assist people with motor diseases, and to explore the potentiality of EEG signals, making the EEG-based HMI more robust and faster, aiming at using it to help individuals with severe motor dysfunctions.

The preserved autonomic functions may provide the asymptomatic clinical status in heart failure despite advanced left ventricular systolic dysfunction.

PubMed

Kocaman, Sinan Altan; Taçoy, Gülten; Ozdemir, Murat; Açıkgöz, Sadık Kadri; Cengel, Atiye

2010-12-01

Autonomic dysfunction is an important marker of prognosis in congestive heart failure (CHF) and may determine the symptoms and progression of CHF. The aim of our study was to investigate whether preserved autonomic function assessed by heart rate variability (HRV) analyses is related to absence of CHF symptoms despite prominently reduced systolic function. The study had a cross-sectional observational design. Fifty patients with left ventricular ejection fraction (EF) below 40% were enrolled. The patients were divided into two groups according to their CHF symptomatic status as Group 1 (NYHA functional class I, asymptomatic group) and Group 2 (NYHA functional class ≥ II, symptomatic group). Plasma C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) levels, echocardiographic parameters and HRV indices were measured while the patients were clinically stable in each group. Possible factors associated with the development of CHF symptoms were assessed by using multiple regression analysis. Baseline clinical characteristics and left ventricular EF were similar in the two groups. Serum CRP (15 ± 21 vs 7 ± 18 mg/L, p=0.011) and NT-proBNP levels (1935 ± 1088 vs 1249 ± 1083 pg/mL, p=0.020) were significantly higher in symptomatic group. The HRV parameters (SDNN: 78 ± 57 vs 122 ± 42 ms, p=0.001; SDANN: 65 ± 55 vs 84 ± 38 ms, p=0.024; SDNNi: 36 ± 41 vs 70 ± 46 ms, p<0.001; triangular index [Ti]: 17 ± 12 vs 32 ± 14, p<0.001) were also significantly depressed in symptomatic group. When multiple regression analysis was performed, only HRV indices of autonomic function were significantly associated with the asymptomatic status (SDNN, OR: 1.016, 95%CI: 1.002-1.031, p=0.028; SDNNi, OR: 1.030, 95%CI: 1.008-1.052, p=0.006; TI, OR: 1.088, 95%CI: 1.019-1.161, p=0.011). Preserved autonomic functions were shown to be associated with absence of CHF symptoms independently of angiotensin converting enzyme inhibitor/angiotensin receptor blocker's treatment and BNP levels and may be protective against the development of CHF symptoms despite advanced left ventricular systolic dysfunction.

Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults.

PubMed

Luttmann-Gibson, Heike; Suh, Helen H; Coull, Brent A; Dockery, Douglas W; Sarnat, Stefanie Ebelt; Schwartz, Joel; Stone, Peter H; Gold, Diane R

2010-09-01

Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects. 25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM(2.5)) and sulphate (SO(4)(2-)) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status. A 5.8 mg/l elevation in CRP was associated with decreases of between -8% and -33% for time and frequency domain HRV outcomes. A 5.1 microg/m(3) increase in SO(4)(2-) on the day before the health assessment was associated with a decrease of -6.7% in the SD of normal RR intervals (SDNN) (95% CI -11.8% to -1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM(2.5). Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation.

The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions.

PubMed

Rasmussen, Mikkel Mylius; Rawashdeh, Yazan F; Clemmensen, Dorte; Tankisi, Hatice; Fuglsang-Frederiksen, Anders; Krogh, Klaus; Christensen, Peter

2015-02-01

The artificial somato-autonomic reflex arch (Xiao procedure) was proposed as treatment for neurogenic bladder dysfunction. We investigated the effects of the procedure on lower urinary tract function. Seven and 3 patients with a median age of 46 years (range 19 to 64) had AIS A and B spinal cord injury, respectively. In these patients an anastomosis was created between the ventral (motor) part of L5 and the ventral part of the S2 root. Urodynamics were performed and a standard questionnaire was completed at baseline and 18 months postoperatively. Artificial reflex arch stimulation did not initiate voiding or increase bladder pressure. Maximum bladder capacity did not change significantly from baseline to followup (median 427.5 ml, range 168 to 581 vs 498.5, range 271 to 580, p = 0.09). Likewise, bladder compliance did not significantly differ at baseline and followup (median 16.9 ml/cm H2O, range 15.0 to 65.0 vs 25.1, range 17.5 to 50.0, p = 0.95). No difference was found in awareness of bladder emptying, incontinence episodes, bladder emptying method or medication use for neurogenic bladder dysfunction. The only statistically significant change was a decreased incidence of leakage at followup on urodynamics (p = 0.03). Postoperatively decreased genital sensation and erectile dysfunction developed in 1 patient and another experienced a minor cerebrovascular accident with no long-term complications. In contrast to earlier findings, creation of an artificial somato-autonomic reflex arch in patients with spinal cord injury had no clinically relevant effect on lower urinary tract function. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The expanding universe of disorders of the basal ganglia.

PubMed

Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

2014-08-09

The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lack of association of the serotonin transporter polymorphism with the sudden infant death syndrome in the San Diego Dataset.

PubMed

Paterson, David S; Rivera, Keith D; Broadbelt, Kevin G; Trachtenberg, Felicia L; Belliveau, Richard A; Holm, Ingrid A; Haas, Elisabeth A; Stanley, Christina; Krous, Henry F; Kinney, Hannah C; Markianos, Kyriacos

2010-11-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS.

Lack of Association of the Serotonin Transporter Polymorphism With the Sudden Infant Death Syndrome in the San Diego Dataset

PubMed Central

Paterson, David S.; Rivera, Keith D.; Broadbelt, Kevin G.; Trachtenberg, Felicia L.; Belliveau, Richard A.; Holm, Ingrid A.; Haas, Elisabeth A.; Stanley, Christina; Krous, Henry F.; Kinney, Hannah C.; Markianos, Kyriacos

2011-01-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS. PMID:20661167

Clinical classification and neuro-vestibular evaluation in chronic dizziness.

PubMed

Oh, Sun-Young; Kim, Do-Hyung; Yang, Tae-Ho; Shin, Byoung-Soo; Jeong, Seul-Ki

2015-01-01

This study attempts to clarify the clinical characteristics of chronic dizziness and its relationships with specific vestibular, oculomotor, autonomic and psychiatric dysfunctions. 73 Patients with idiopathic chronic dizziness were recruited and classified based on history taking and clinical examination into the following four clinical subgroups; vestibular migraine (VM), dysautonomia, psychogenic, and unspecified groups. They were also evaluated using oculomotor, otolithic and autonomic function tests, and psychologic investigation. Patients in the VM group showed a high proportion of abnormality on smooth pursuit and otolithic function testing compared to the other groups. The dysautonomia group revealed significant abnormalities in sympathetic and cardiovagal autonomic function, while the psychogenic group had a high frequency of abnormality in sympathetic autonomic testing and in Beck's anxiety inventory scale. The unspecified group showed abnormalities on saccade, smooth pursuit and autonomic function testing. Clinical classification of patients with chronic dizziness was relevant and they showed a correlation with disease-specific abnormal results in oculomotor, otolithic, autonomic function and psychology testing. Appropriate diagnostic investigation based on precise clinical diagnosis of chronic dizziness reduces the need for extensive laboratory testing, neuroimaging, and other low-yield tests. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Anxiety, depression and autonomic nervous system dysfunction in hypertension.

PubMed

Bajkó, Zoltán; Szekeres, Csilla-Cecília; Kovács, Katalin Réka; Csapó, Krisztina; Molnár, Sándor; Soltész, Pál; Nyitrai, Erika; Magyar, Mária Tünde; Oláh, László; Bereczki, Dániel; Csiba, László

2012-06-15

This study examined the relationship between autonomic nervous system dysfunction, anxiety and depression in untreated hypertension. 86 newly diagnosed hypertensive patients and 98 healthy volunteers were included in the study. The psychological parameters were assessed with Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory by a skilled psychologist. Autonomic parameters were examined during tilt table examination (10min lying position, 10min passive tilt). Heart rate variability (HRV) was calculated by autoregressive methods. Baroreflex sensitivity (BRS) was calculated by non-invasive sequence method from the recorded beat to beat blood pressure values and RR intervals. Significantly higher state (42.6±9.3 vs. 39.6±10.7 p=0.05) and trait (40.1±8.9 vs. 35.1±8.6, p<0.0001) anxiety scores were found in the hypertension group. There was no statistically significant difference in the depression level. LF-RRI (Low Frequency-RR interval) of HRV in passive tilt (377.3±430.6 vs. 494.1±547, p=0.049) and mean BRS slope (11.4±5.5 vs. 13.2±6.4, p=0.07) in lying position were lower in hypertensives. Trait anxiety score correlates significantly with sympatho/vagal balance (LF/HF-RRI) in passive tilt position (Spearman R=-0.286, p=0.01). Anxiety could play a more important role than depression in the development of hypertension. Altered autonomic control of the heart could be one of the pathophysiological links between hypertension and psychological factors. Copyright © 2012 Elsevier B.V. All rights reserved.

Monozygotic twins discordant for ROHHAD phenotype.

PubMed

Patwari, Pallavi P; Rand, Casey M; Berry-Kravis, Elizabeth M; Ize-Ludlow, Diego; Weese-Mayer, Debra E

2011-09-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) falls within a group of pediatric disorders with both respiratory control and autonomic nervous system dysregulation. Children with ROHHAD typically present after 1.5 years of age with rapid weight gain as the initial sign. Subsequently, they develop alveolar hypoventilation, autonomic nervous system dysregulation, and, if untreated, cardiorespiratory arrest. To our knowledge, this is the first report of discordant presentation of ROHHAD in monozygotic twins. Twin girls, born at term, had concordant growth and development until 8 years of age. From 8 to 12 years of age, the affected twin developed features characteristic of ROHHAD including obesity, alveolar hypoventilation, scoliosis, hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, premature pubarche, and growth hormone deficiency), right paraspinal/thoracic ganglioneuroblastoma, seizures, and autonomic dysregulation including altered pain perception, large and sluggishly reactive pupils, hypothermia, and profound bradycardia that required a cardiac pacemaker. Results of genetic testing for PHOX2B (congenital central hypoventilation syndrome disease-defining gene) mutations were negative. With early recognition and conservative management, the affected twin had excellent neurocognitive outcome that matched that of the unaffected twin. The unaffected twin demonstrated rapid weight gain later in age but not development of signs/symptoms consistent with ROHHAD. This discordant twin pair demonstrates key features of ROHHAD including the importance of early recognition (especially hypoventilation), complexity of signs/symptoms and clinical course, and importance of initiating comprehensive, multispecialty care. These cases confound the hypothesis of a monogenic etiology for ROHHAD and indicate alternative etiologies including autoimmune or epigenetic phenomenon or a combination of genetic predisposition and acquired precipitant.

Increased interarm blood pressure difference is associated with autonomic dysfunction and atherosclerosis in patients with chest pain and no history of coronary artery disease.

PubMed

Hwang, Hui-Jeong; Sohn, Il Suk; Kim, Dong-Hee; Park, Chang-Bum; Cho, Jin-Man; Kim, Chong-Jin

2017-08-15

Interarm blood pressure (BP) difference has been reported to be associated with atherosclerosis and increased cardiovascular death. We were to investigate associations of interarm systolic blood pressure (SBP) difference with heart rate recovery (HRR) after exercise, an index of autonomic function, and carotid atherosclerotic markers, and to evaluate the association of interarm SBP difference with concurrent coronary artery disease (CAD). A total of 995 consecutive patients who underwent treadmill stress echocardiography with chest pain but no history of CAD were enrolled. Interarm SBP difference, carotid intima-media thickness (IMT) and plaque were measured before exercise, and HRR 2min following exercise was assessed. Suspected CAD was defined as newly developed wall motion abnormalities after treadmill exercise. Patients with an interarm SBP difference≥10mmHg had higher prevalence of hypertension, increased right and left SBP, right diastolic BP, mean arterial pressure, body mass index and carotid IMT, existent carotid plaque, lower metabolic equivalents and slower HRR. Interarm SBP difference≥10mmHg was independently associated with slower HRR and existent carotid plaque. Suspected CAD was associated with existent carotid plaque or slower HRR, but not with an interarm SBP difference≥10mmHg. Increased interarm SBP difference was associated with lower autonomic modulation and carotid atherosclerosis in patients with chest pain and no history of CAD, but not with suspected CAD. Observed adverse prognosis in patients with increased interarm BP difference might result from long-term persistent autonomic dysfunction and atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

PubMed

Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso

2014-08-01

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.

The relation of autonomic function to physical fitness in patients suffering from alcohol dependence.

PubMed

Herbsleb, Marco; Schulz, Steffen; Ostermann, Stephanie; Donath, Lars; Eisenträger, Daniela; Puta, Christian; Voss, Andreas; Gabriel, Holger W; Bär, Karl-Jürgen

2013-10-01

Reduced cardio-vascular health has been found in patients suffering from alcohol dependence. Low cardio-respiratory fitness is an independent predictor of cardio-vascular disease. We investigated physical fitness in 22 alcohol-dependent patients 10 days after acute alcohol withdrawal and compared results with matched controls. The standardized 6-min walk test (6 MWT) was used to analyze the relationship of autonomic dysfunction and physical fitness. Ventilatory indices and gas exchanges were assessed using a portable spiroergometric system while heart rate recordings were obtained separately. We calculated walking distance, indices of heart rate variability and efficiency parameters of heart rate and breathing. In addition, levels of exhaled carbon monoxide were measured in all participants to account for differences in smoking behaviour. Multivariate analyses of variance (MANOVA) were performed to investigate differences between patients and controls with regard to autonomic and efficiency parameters. Patients walked a significantly shorter distance in comparison to healthy subjects during the 6 MWT. Significantly decreased heart rate variability was observed before and after the test in patients when compared to controls, while no such difference was observed during exercise. The efficiency parameters indicated significantly reduced efficiency in physiological regulation when the obtained parameters were normalized to the distance. The 6 MWT is an easily applied instrument to measure physical fitness in alcohol dependent patients. It can also be used during exercise interventions. Reduced physical fitness, as observed in our study, might partly be caused by autonomic dysfunction, leading to less efficient regulation of physiological processes during exercise. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An outbreak of foodborne botulism in Ontario

PubMed Central

Loutfy, Mona R; Austin, John W; Blanchfield, Burke; Fong, Ignatius W

2003-01-01

Botulism is a rare paralytic illness resulting from a potent neurotoxin produced by Clostridium botulinum. Botulism in Canada is predominately due to C botulinum type E and affects mainly the First Nations and Inuit populations. The most recent outbreak of botulism in Ontario was in Ottawa in 1991 and was caused by C botulinum type A. We report an outbreak of foodborne type B botulism in Ontario, which implicated home-canned tomatoes. The outbreak was characterized by mild symptoms in two cases and moderately severe illness in one case. The investigation shows the importance of considering the diagnosis of botulism in patients presenting with cranial nerve and autonomic dysfunction, especially when combined with gastrointestinal complaints; it also highlights the importance of proper home canning technique. PMID:18159458

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Central insulin and leptin-mediated autonomic control of glucose homeostasis

USDA-ARS?s Scientific Manuscript database

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucos...

Anesthesia in a pediatric patient with ROHADD syndrome.

PubMed

Esparza Isasa, E; Palomero Rodríguez, M A; Acebedo Bambaren, I; Medrano Viñas, C; Gil Mayo, D; Domínguez Pérez, F; Pestaña Lagunas, D

2018-05-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare entity that is characterised by its onset in healthy children at 2-4 years of age. It is a complex syndrome that includes, among other symptoms, rapid weight gain with hyperphagia, hypothalamic dysfunction, central hypoventilation, and autonomic dysregulation. The case is presented of a 10-year-old boy with a diagnosis of ROHHAD syndrome undergoing insertion of a port-a-cath under general anaesthesia, who developed complications during the anaesthetic procedure related to his illness. The peri-operative management of these patients represents a challenge for the anaesthetist, given the involvement of multiple systems and the frequent respiratory comorbidities associated with them. A summary is presented of some of the implications and anaesthetic considerations that must be taken into account in the management of these patients. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?

PubMed Central

Ewing, Graham E.

2009-01-01

There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines. PMID:22666668

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington's Disease.

PubMed

Wang, Huei-Bin; Loh, Dawn H; Whittaker, Daniel S; Cutler, Tamara; Howland, David; Colwell, Christopher S

2018-01-01

Huntington's disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays.

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Postural tachycardia syndrome: time frequency mapping

NASA Technical Reports Server (NTRS)

Novak, V.; Novak, P.; Opfer-Gehrking, T. L.; Low, P. A.

1996-01-01

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation of heart rate: evidence from spectral analysis of heart rate variability.

PubMed

Chen, Jin-Long; Chiu, Hung-Wen; Tseng, Yin-Jiun; Chu, Woei-Chyn

2006-06-01

The clinical manifestations of hyperthyroidism resemble those of the hyperadrenergic state. This study was designed to evaluate the impact of hyperthyroidism on the autonomic nervous system (ANS) and to investigate the relationship between serum thyroid hormone concentrations and parameters of spectral heart rate variability (HRV) analysis in hyperthyroidism. Thirty-two hyperthyroid Graves' disease patients (mean age 31 years) and 32 sex-, age-, and body mass index (BMI)-matched normal control subjects were recruited to receive one-channel electrocardiogram (ECG) recording. The cardiac autonomic nervous function was evaluated by the spectral analysis of HRV, which indicates the autonomic modulation of the sinus node. The correlation coefficients between serum thyroid hormone concentrations and parameters of the spectral HRV analysis were also computed. The hyperthyroid patients revealed significant differences (P < 0.001) compared with the controls in the following HRV parameters: a decrease in total power (TP), very low frequency power (VLF), low frequency power (LF), high frequency power (HF), and HF in normalized units (HF%); and an increase in LF in normalized units (LF%) and in the ratio of LF to HF (LF/HF). After correction of hyperthyroidism in 28 patients, all of the above parameters were restored to levels comparable to those of the controls. In addition, serum thyroid hormone concentrations showed significant correlations with spectral HRV parameters. Hyperthyroidism is in a sympathovagal imbalanced state, characterized by both increased sympathetic and decreased vagal modulation of the heart rate. These autonomic dysfunctions can be detected simultaneously by spectral analysis of HRV, and the spectral HRV parameters could reflect the disease severity in hyperthyroid patients.

Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke.

PubMed

Payne, Peter; Fiering, Steven; Leiter, James C; Zava, David T; Crane-Godreau, Mardi A

2017-01-01

This single-arm non-randomized pilot study explores an intervention to improve the health of flight attendants (FA) exposed to second-hand cigarette smoke prior to the smoking ban on commercial airlines. This group exhibits an unusual pattern of long-term pulmonary dysfunction. We report on Phase I of a two-phase clinical trial; the second Phase will be a randomized controlled trial testing digital delivery of the intervention. Subjects were recruited in the Northeastern US; testing and intervention were administered in 4 major cities. The intervention involved 12 h of training in Meditative Movement practices. Based on recent research on the effects of nicotine on fear learning, and the influence of the autonomic nervous system on immune function, our hypothesis was that this training would improve autonomic function and thus benefit a range of health measures. Primary outcomes were the 6-min walk test and blood levels of C-reactive protein. Pulmonary, cardiovascular, autonomic, and affective measures were also taken. Fourteen participants completed the training and post-testing. There was a 53% decrease in high sensitivity C-Reactive Protein ( p ≤ 0.05), a 7% reduction in systolic blood pressure ( p ≤ 0.05), a 13% increase in the 6-min walk test ( p ≤ 0.005), and significant positive changes in several other outcomes. These results tend to confirm the hypothesized benefits of MM training for this population, and indicate that autonomic function may be important in the etiology and treatment of their symptoms. No adverse effects were reported. This trial is registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02612389/), and is supported by a grant from the Flight Attendant Medical Research Institute (FAMRI).

Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial).

PubMed

Cho, Yoon Hi; Craig, Maria E; Davis, Elizabeth A; Cotterill, Andrew M; Couper, Jennifer J; Cameron, Fergus J; Benitez-Aguirre, Paul Z; Dalton, R Neil; Dunger, David B; Jones, Timothy W; Donaghue, Kim C

2015-04-01

This study examined the association between cardiac autonomic dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1 diabetes. Adolescents recruited as part of a multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration 6.9 years; mean HbA1c 8.4%, 68 mmol/mol) underwent a 10-min continuous electrocardiogram recording for heart rate variability analysis. Time-domain heart rate variability measures included baseline heart rate, SD of the R-R interval (SDNN), and root mean squared difference of successive R-R intervals (RMSSD). Spectral analysis included sympathetic (low-frequency) and parasympathetic (high-frequency) components. Standardized ACR were calculated from six early morning urine collections using an established algorithm, reflecting age, sex, and duration, and stratified into ACR tertiles, where the upper tertile reflects higher nephropathy risk. The upper-tertile ACR group had a faster heart rate (76 vs. 73 bpm; P < 0.01) and less heart rate variability (SDNN 68 vs. 76 ms, P = 0.02; RMSSD 63 vs. 71 ms, P = 0.04). HbA1c was 8.5% (69 mmol/mmol) in the upper tertile vs. 8.3% (67 mmol/mol) in the lower tertiles (P = 0.07). In multivariable analysis, upper-tertile ACR was associated with faster heart rate (β = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD (β = -9.5, 95% CI -18.2 to -0.8, P = 0.03), independent of age and HbA1c. Adolescents at potentially higher risk for nephropathy show an adverse cardiac autonomic profile, indicating sympathetic overdrive, compared with the lower-risk group. Longitudinal follow-up of this cohort will further characterize the relationship between autonomic and renal dysfunction and the effect of interventions in this population. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

PubMed Central

Salari, Mehri; Fayyazi, Emad; Mirmosayyeb, Omid

2016-01-01

Currently, gastrointestinal (GI) dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA) and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed. PMID:28331512

Particles Alter Diesel Exhaust Gases-Induced Hypotension, Cardiac Arrhythmia,Conduction Disturbance, and Autonomic Imbalance in Heart Failure-Prone Rats

EPA Science Inventory

Epidemiologic studies indicate that acute exposures to vehicular traffic and particulate matter (PM) air pollution are key causes of fatal cardiac arrhythmia, especially in those with preexisting cardiovascular disease. Researchers point to electrophysiologic dysfunction and auto...

Insular Alzheimer disease pathology and the psychometric correlates of mortality.

PubMed

Royall, Donald R

2008-03-01

Right hemisphere dysfunction is associated with mortality in Alzheimer's disease (AD) and other neurologic conditions. These associations may be mediated by insular pathology, as insular lesions result in demonstrable changes in cardiovascular and autonomic control. AD affects the insulae at a preclinical stage, and insular AD pathology may be present in up to 40% of nondemented septuagenarians and octogenarians. This pathology can affect in vivo cardiac conduction and thereby dispose to cardiac arrhythmias and sudden death. Thus, AD pathology should be considered as a possible explanation for autonomic morbidity and mortality in nondemented elderly persons.

The Phantom in our opera - or the hidden ways of the autonomic nervous system in cardiac patients

PubMed Central

van Tellingen, C.

2004-01-01

The role of the autonomic nervous system in the understanding of pathophysiological mechanisms in a variety of cardiovascular clinico-pathological conditions is highlighted from a clinician's point of view with the focus on coronary mimicry, enhanced sympathetic tone and syndrome X. A unique case is presented where sinus node dysfunction in pandysautonomia seemed to be an early sign of hypothalamic glioblastoma. In addition, relevant literature on this topic is addressed to put distinct clinical patterns into a broader perspective. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696275

High mortality from Guillain-Barré syndrome in Bangladesh.

PubMed

Ishaque, Tanveen; Islam, Mohammad B; Ara, Gulshan; Endtz, Hubert P; Mohammad, Quazi D; Jacobs, Bart C; Islam, Zhahirul

2017-06-01

Although Guillain-Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6-30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1-16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02-5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1-3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05-3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5-19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves. © 2017 Peripheral Nerve Society.

Serotonin toxicity as a consequence of linezolid use in revision hip arthroplasty.

PubMed

Mason, Lyndon W; Randhawa, Kiran S; Carpenter, Eleanor C

2008-11-01

Linezolid is the first in a new group of antibiotics called oxazolidinones. As a potent antimicrobial, it has activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, penicillin-resistant Streptococcus pneumoniae, and macrolide-resistant streptococci. There are several documented case reports of serotonin toxicity when used with selective serotonin reuptake inhibitors. The symptoms of serotonin syndrome are alteration of mental state, autonomic dysfunction, and neuromuscular disorders. This article presents a case of an interaction of the serotonin reuptake inhibitor venlafaxine and linezolid and the possible diagnostic problems that can occur. A 58-year-old woman presented with signs of systemic infection. Her medical history included bladder resection for transitional cell carcinoma, bilateral total hip arthroplasty (THA), and depression, for which she was on venlafaxine. Serological and imaging investigations revealed MRSA infection of the bilateral THA. The patient was started on vancomycin and rifampicin intravenously. As intravenous access was becoming problematic and long-term antibiotics were needed, treatment was changed to oral linezolid and oral rifampicin. Four days after the commencement of linezolid, the patient was acutely disorientated with generalized cerebellar signs and no autonomic dysfunction. A computed tomography scan of the head and lumbar puncture revealed no abnormal findings. A diagnosis of serotonin toxicity was made. The patient recovered when linezolid and venlafaxine were discontinued and supportive measures were provided. Linezolid is a popular choice of antibiotic, especially for the treatment of orthopedic-related MRSA infections. Patients who commonly require linezolid as an antimicrobial are those with complex infections where other antibiotic treatment has failed. It is therefore important to be vigilant with linezolid use. Physicians should be aware of the nonspecific presentation of serotonin symptoms and the treatment.

Etiologic theories of idiopathic scoliosis. Somatic nervous system and the NOTOM escalator concept as one component in the pathogenesis of adolescent idiopathic scoliosis.

PubMed

Burwell, R G; Dangerfield, P H; Freeman, B J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). In recent years encouraging advances thought to be related to the pathogenesis of AIS have been made in several fields. After reviewing concepts of AIS pathogenesis we formulated a collective model of pathogenesis. The central concept of this collective model is a normal neuro-osseous timing of maturation (NOTOM) system operating in a child's internal world during growth and maturation; this provides a dynamic physiological balance of postural equilibrium continuously renewed between two synchronous, polarized processes (NOTOM escalator) linked through sensory input and motor output, namely: 1) osseous escalator-increasing skeletal size and relative segmental mass, and 2) neural escalator - including the CNS body schema. The latter is recalibrated continuously as the body adjusts to biomechanical and kinematic changes resulting from skeletal enlargement, enabling it to coordinate motor actions. We suggest that AIS progression results from abnormality of the neural and/or osseous components of these normal escalator in time and/or space - as asynchrony and/or asymmetries - which cause a failure of neural systems to control asymmetric growth of a rapidly enlarging and moving adolescent spine. This putative initiating asymmetric growth in the spine is explained in separate papers as resulting from dysfunction of the hypothalamus expressed through the sympathetic nervous system (leptin-sympathetic nervous system concept for AIS pathogenesis). In girls, the expression of AIS may result from disharmony between the somatic and autonomic nervous systems - relative postural maturational delay in the somatic nervous system and hypothalamic dysfunction in the autonomic nervous system, with the conflict being fought out in the spine and trunk of the girl and compounded by biomechanical spinal growth modulation.

Interoceptive inference: From computational neuroscience to clinic.

PubMed

Owens, Andrew P; Allen, Micah; Ondobaka, Sasha; Friston, Karl J

2018-04-22

The central and autonomic nervous systems can be defined by their anatomical, functional and neurochemical characteristics, but neither functions in isolation. For example, fundamental components of autonomically mediated homeostatic processes are afferent interoceptive signals reporting the internal state of the body and efferent signals acting on interoceptive feedback assimilated by the brain. Recent predictive coding (interoceptive inference) models formulate interoception in terms of embodied predictive processes that support emotion and selfhood. We propose interoception may serve as a way to investigate holistic nervous system function and dysfunction in disorders of brain, body and behaviour. We appeal to predictive coding and (active) interoceptive inference, to describe the homeostatic functions of the central and autonomic nervous systems. We do so by (i) reviewing the active inference formulation of interoceptive and autonomic function, (ii) survey clinical applications of this formulation and (iii) describe how it offers an integrative approach to human physiology; particularly, interactions between the central and peripheral nervous systems in health and disease. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity

PubMed Central

de Sant Anna Junior, Maurício; Carneiro, João Regis Ivar; Carvalhal, Renata Ferreira; Torres, Diego de Faria Magalhães; da Cruz, Gustavo Gavina; Quaresma, José Carlos do Vale; Lugon, Jocemir Ronaldo; Guimarães, Fernando Silva

2015-01-01

Background Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation. Objective This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals. Methods Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student’s t-test, with a level of significance of 5%. Results Obese subjects had lower values of SDNN (40.0 ± 18.0 ms vs. 70.0 ± 27.8 ms; p = 0.0004), RMSSD (23.7 ± 13.0 ms vs. 40.3 ± 22.4 ms; p = 0.0030), pNN50 (14.8 ± 10.4 % vs. 25.9 ± 7.2%; p = 0.0061) and HF (30.0 ± 17.5 Hz vs. 51.7 ± 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 ± 2.8 vs. 1.0 ± 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 ± 30.2 Hz vs. 40.9 ± 23.9 Hz; p = 0.9013). Conclusion morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction. PMID:26536979

The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system

PubMed Central

Chaverra, Marta; George, Lynn; Thorne, Julian; Grindeland, Andrea; Ueki, Yumi; Eiger, Steven; Cusick, Cassie; Babcock, A. Michael; Carlson, George A.

2017-01-01

ABSTRACT Hereditary sensory and autonomic neuropathies (HSANs) are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS) dysfunction. HSAN type III, known as familial dysautonomia (FD), results from a single base mutation in the gene IKBKAP that encodes a scaffolding unit (ELP1) for a multi-subunit complex known as Elongator. Since mutations in other Elongator subunits (ELP2 to ELP4) are associated with central nervous system (CNS) disorders, the goal of this study was to investigate a potential requirement for Ikbkap in the CNS of mice. The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40. While signs and pathology of FD have been noted in the CNS, the clinical and research focus has been on the sensory and autonomic dysfunction, and no genetic model studies have investigated the requirement for Ikbkap in the CNS. Here, we report, using a novel mouse line in which Ikbkap is deleted solely in the nervous system, that not only is Ikbkap widely expressed in the embryonic and adult CNS, but its deletion perturbs both the development of cortical neurons and their survival in adulthood. Primary cilia in embryonic cortical apical progenitors and motile cilia in adult ependymal cells are reduced in number and disorganized. Furthermore, we report that, in the adult CNS, both autonomic and non-autonomic neuronal populations require Ikbkap for survival, including spinal motor and cortical neurons. In addition, the mice developed kyphoscoliosis, an FD hallmark, indicating its neuropathic etiology. Ultimately, these perturbations manifest in a developmental and progressive neurodegenerative condition that includes impairments in learning and memory. Collectively, these data reveal an essential function for Ikbkap that extends beyond the peripheral nervous system to CNS development and function. With the identification of discrete CNS cell types and structures that depend on Ikbkap, novel strategies to thwart the progressive demise of CNS neurons in FD can be developed. PMID:28167615

Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge

PubMed Central

Silvia, Paul J.; Nusbaum, Emily C.; Eddington, Kari M.; Beaty, Roger E.; Kwapil, Thomas R.

2014-01-01

Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a “do your best” challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task’s goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work. PMID:25431505

Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

PubMed

Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

2018-01-17

Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group (P < 0.05). PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

[Neurotic disorders in members of engine crews].

PubMed

Kazakov, V E

2004-01-01

338 members of engine crews were observed. 159 were found to have neurotic and anxious-phobic reactions before any clinical nosology. It was established that misunderstanding between engine driver and his helpmate, autonomic dysfunction, individual features of character and family conflicts play the main part in the development of neurotic reactions.

Tolerance to Central Hypovolemia: The Influence of Oscillations in Arterial Pressure and Cerebral Blood Velocity

DTIC Science & Technology

2011-10-01

specific details about whether they were taking oral contraceptive medications, both of which can impact cardiovascular responses to hypovo- lemia (4, 20...Gerontology 49: 279–286, 2003. 59. Stewart JM. Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and

Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

EPA Science Inventory

The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

Hypotension and AV block after diesel exhaust exposure in heart failure-prone rats: role of gaseous and particulate components

EPA Science Inventory

Acute inhalations ofdiesel engine exhaust (DE) and fine particulate matter (PM2.5) have been demonstrated to provoke adverse cardiac events in humans with preexisting heart disease. Electrophysiologic dysfunction and autonomic imbalance are among the mechanisms widely held to und...

Affective and Autonomic Responses to Erotic Images: Evidence of Disgust-Based Mechanisms in Female Sexual Interest/Arousal Disorder.

PubMed

DePesa, Natasha S; Cassisi, Jeffrey E

2017-09-01

Disgust has recently been implicated in the development and maintenance of female sexual dysfunction, yet most empirical studies have been conducted with a sexually healthy sample. The current study contributes to the literature by expanding the application of a disgust model of sexual functioning to a clinically relevant sample of women with low sexual desire/arousal and accompanying sexual distress. Young women (mean age = 19.12 years) with psychometrically defined sexual dysfunction (i.e., female sexual interest/arousal disorder [FSIAD] group) and a healthy control group were compared in their affective (i.e., facial electromyography [EMG] and self-report) and autonomic (i.e., heart rate and electrodermal activity) responses to disgusting, erotic, positive, and neutral images. Significant differences were predicted in responses to erotic images only. Specifically, it was hypothesized that the FSIAD group would display affective and autonomic responses consistent with a disgust response, while responses from the control group would align with a general appetitive response. Results largely supported study hypotheses. The FSIAD group displayed significantly greater negative facial affect, reported more subjective disgust, and recorded greater heart rate deceleration than the control group in response to erotic stimuli. Greater subjective disgust response corresponded with more sexual avoidance behavior. Planned follow-up analyses explored correlates of subjective disgust responses.

Dysautonomia, a heuristic approach to a revised model for etiology of disease.

PubMed

Lonsdale, Derrick

2009-03-01

Dysautonomia refers to a disease where the autonomic nervous system is dysfunctional. This may be a central control mechanism, as in genetically determined familial dysautonomia (Riley-Day Syndrome), or peripherally in the distribution of the sympathetic and parasympathetic systems. There are multiple reports of a number of different diseases associated with dysautonomia. The etiology of this association has never been explained. There are also multiple publications on dysautonomia associated with specific non-caloric nutritional deficiencies. Beriberi is the prototype of autonomic dysfunction. It is the best known nutritional deficiency disease caused by an imbalance between ingested calories and the vitamins required for their oxidation, particularly thiamin. Long thought to be abolished in modern medical thinking, there are occasional isolated reports of the full-blown disease in developed Western cultures. Apart from genetically and epigenetically determined disease, evidence is presented that marginal high calorie malnutrition, particularly with reference to simple carbohydrates, is responsible for widespread dysautonomia. The brain and heart are the organs that have a fast rate of oxidative metabolism and are affected early by any mechanism that reduces oxidative efficiency. It is hypothesized that this results in a chaotic state of the hypothalamic/autonomic/endocrine axis. Due to the lack of adequate automatic controls, this may be responsible in some cases for breakdown of organ systems through long-standing energy deficiency, thus leading eventually to organic disease.

Autonomic deficit not the cause of death in West Nile virus neurological disease.

PubMed

Wang, Hong; Siddharthan, Venkatraman; Hall, Jeffery O; Morrey, John D

2014-02-01

Some West Nile virus (WNV)-infected patients have been reported to manifest disease signs consistent with autonomic dysfunction. Moreover, WNV infection in hamsters causes reduced electromyography amplitudes of the gastrointestinal tract and diaphragm, and they have reduced heart rate variability (HRV), a read-out for the parasympathetic autonomic function. HRV was measured in both hamsters and mice using radiotelemetry to identify autonomic deficits. To identify areas of WNV infection within the medulla oblongata mapping to the dorsal motor nucleus of vagus (DMNV) and the nucleus ambiguus (NA), fluorogold dye was injected into the cervical trunk of the vagus nerve of hamsters. As a measurement of the loss of parasympathetic function, tachycardia was monitored contiguously over the time course of the disease. Decrease of HRV did not occur in all animals that died, which is not consistent with autonomic function being the mechanism of death. Fluorogold-stained cells in the DMNV were not stained for WNV envelope protein. Fourteen percent of WNV-stained cells were co-localized with fluorogold-stained cells in the NA. These data, however, did not suggest a fatal loss of autonomic functions because tachycardia was not observed in WNV-infected hamsters. Parasympathetic autonomic function deficit was not a likely mechanism of death in WNV-infected rodents and possibly in human patients with fatal WN neurological disease.

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

PubMed

Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

2015-07-14

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease.

PubMed

Engel, Tal; Ben-Horin, Shomron; Beer-Gabel, Marc

2015-10-01

Autonomic dysfunction has been implicated in Crohn's disease (CD). We aimed to investigate heart rate variability (HRV) as a marker of possible autonomic imbalance in patients with CD. Thirty patients with CD and 30 age- and gender-matched healthy controls were enrolled in a prospective cohort study and underwent HRV study. Anxiety level was scored using the STAI questionnaire and CD clinical activity was assessed by Harvey-Bradshaw index. Blood tests including inflammatory markers were obtained for all participants. CD subjects had lower mean blood pressure (85.51 ± 11.07 mm Hg, 91.51 ± 6.99, P = 0.015) and albumin and significantly higher CRP and IL-6 compared with controls (P < 0.002 for all comparisons). Mean HRV values of very low-frequency power and low-frequency power components were significantly lower among CD subjects (P = 0.038 and 0.027, respectively), implying a predominant sympathetic tone. Anxiety level scores were significantly higher among patients with CD for both state anxiety (P = 0.001) and trait anxiety (P < 0.0001). However, patients with active disease had similar anxiety scores as patients in remission, yet had a significantly lower BMI, lower albumin level, and higher CRP and IL-6 levels (P < 0.05 for all comparisons). Moreover, despite similar anxiety scores, patients with active disease had higher pulse rate (P = 0.02) and lower HRV indexes, which correlated with albumin levels(r = 0.7, P = 0.001). Although patients with CD have higher anxiety levels compared with controls, they exhibit depressed HRV independent of this anxiety state and in direct correlation with disease activity and inflammatory markers. These observations suggest an inherent imbalance of autonomic function associated with active inflammation.

Longitudinal assessment of excessive daytime sleepiness in early Parkinson's disease.

PubMed

Amara, Amy W; Chahine, Lama M; Caspell-Garcia, Chelsea; Long, Jeffrey D; Coffey, Christopher; Högl, Birgit; Videnovic, Aleksandar; Iranzo, Alex; Mayer, Geert; Foldvary-Schaefer, Nancy; Postuma, Ron; Oertel, Wolfgang; Lasch, Shirley; Marek, Ken; Simuni, Tanya

2017-08-01

Excessive daytime sleepiness (EDS) is common and disabling in Parkinson's disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. The Parkinson's Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio. In early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning.

PubMed

Levine, Todd D

2018-01-01

Small fiber neuropathy (SFN) has a poorly understood pathology, but patients would benefit from determination of clinical phenotypes that allows for better diagnosis and treatment planning. I propose that patients should be classified dependent on whether there is sodium channel dysfunction, classic neurologic symptoms only, widespread neuropathic pain, or autonomic symptoms. Patients with SFN can then be considered in light of their clinical phenotype, allowing for focus on subsets of patients who might have diagnosable conditions or be more prone to responding to a particular type of therapy that may not be efficacious in the broader patient population with SFN. There are several therapies currently available that can address the symptoms of SFN; however, to develop novel therapeutic strategies, it will be imperative to classify patients to understand and target the underlying pathology.

Exercise improves cardiac autonomic function in obesity and diabetes.

PubMed

Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

2013-05-01

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine.

PubMed Central

Mukand, J. A.

1991-01-01

Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. PMID:1866948

Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

EPA Science Inventory

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature.

PubMed

Chew, H B; Ngu, L H; Keng, W T

2011-03-01

A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature

PubMed Central

Chew, H B; Ngu, L H; Keng, W T

2011-01-01

A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support. PMID:22715259

Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type

PubMed Central

Crestani, Carlos C.

2016-01-01

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress. PMID:27445843

Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review.

PubMed

Zhou, Zhibin; Zhang, Xingwen; Cui, Fang; Liu, Ruozhuo; Dong, Zhao; Wang, Xiaolin; Yu, Shengyuan

2014-01-01

Motor neuron hyperexcitability (MNH) indicates a disorder characterized by an ectopic motor nerve discharge on electromyogram (EMG). Here, we present a series of three cases of subacute MNH with mercury poisoning. The first case showed hyperhidrosis, insomnia, generalied myokymia, cramps, tremor, weight loss, and myokymic and neuromyotonic discharges, followed by encephalopathy with confusion, hallucinations, and memory decrease. The second case was similar to the former but without encephalopathic features. The third case showed widespread fasciculation, fatigue, insomnia, weight loss, and autonomic dysfunction, including constipation, micturition difficulty, and impotence, with multiple fibrillation, unstable fasciculation, widened motor neuron potential, and an incremental response at high-rate stimulation in repetitive nerve stimulation. Based on the symptoms, the three cases were diagnosed as Morvan's syndrome, Isaacs' syndrome, and Lambert-Eaton myasthenic syndrome with ALS-like syndrome, respectively. Mercury poisoning in the three cases was confirmed by analysis of blood and urine samples. All cases recovered several months after chelation therapy and were in good condition at follow-up. Very few cases of MNH linked with mercury exposure have been reported in the literature. The mechanism of mercury-induced MNH may be associated with ion channel dysfunction. © 2014 S. Karger AG, Basel.

The psychosis spectrum in Parkinson disease

PubMed Central

ffytche, Dominic H.; Creese, Byron; Politis, Marios; Chaudhuri, K. Ray; Weintraub, Daniel; Ballard, Clive; Aarsland, Dag

2017-01-01

In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors — for example, autonomic dysfunction — that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis. PMID:28106066

MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

PubMed

Conti, Valentina; Gandaglia, Anna; Galli, Francesco; Tirone, Mario; Bellini, Elisa; Campana, Lara; Kilstrup-Nielsen, Charlotte; Rovere-Querini, Patrizia; Brunelli, Silvia; Landsberger, Nicoletta

2015-01-01

Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

Toll-like receptor 4 promotes autonomic dysfunction, inflammation and microglia activation in the hypothalamic paraventricular nucleus: role of endoplasmic reticulum stress.

PubMed

Masson, Gustavo S; Nair, Anand R; Dange, Rahul B; Silva-Soares, Pedro Paulo; Michelini, Lisete C; Francis, Joseph

2015-01-01

Toll-like receptor 4 (TLR4) signaling induces tissue pro-inflammatory cytokine release and endoplasmic reticulum (ER) stress. We examined the role of TLR4 in autonomic dysfunction and the contribution of ER stress. Our study included animals divided in 6 experimental groups: rats treated with saline (i.v., 0.9%), LPS (i.v., 10mg/kg), VIPER (i.v., 0.1 mg/kg), or 4-PBA (i.p., 10 mg/kg). Two other groups were pretreated either with VIPER (TLR4 viral inhibitory peptide) LPS + VIPER (i.v., 0.1 mg/kg) or 4-Phenyl butyric acid (4-PBA) LPS + PBA (i.p., 10 mg/kg). Arterial pressure (AP) and heart rate (HR) were measured in conscious Sprague-Dawley rats. AP, HR variability, as well as baroreflex sensitivity (BrS), was determined after LPS or saline treatment for 2 hours. Immunofluorescence staining for NeuN, Ib1a, TLR4 and GRP78 in the hypothalamic paraventricular nucleus (PVN) was performed. TNF-α, TLR4 and GRP78 protein expression in the PVN were evaluated by western blot. Plasma norepinephrine levels were determined by ELISA. Acute LPS treatment increased HR and plasma norepinephrine concentration. It also decreased HR variability and high frequency (HF) components of HR variability, as well BrS. Acute LPS treatment increased TLR4 and TNF-α protein expression in the PVN. These hemodynamic and molecular effects were partially abrogated with TLR4 blocker or ER stress inhibitor pretreatment. In addition, immunofluorescence study showed that TLR4 is co-localized with GRP78in the neurons. Further inhibition of TLR4 or ER stress was able to attenuate the LPS-induced microglia activation. TLR4 signaling promotes autonomic dysfunction, inflammation and microglia activation, through neuronal ER stress, in the PVN.

The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance.

PubMed

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Turco, Domenico Del; Seidel, Kay; Dunnen, Wilfred den; Korf, Horst-Werner

2016-01-01

The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.

Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults

PubMed Central

Luttmann-Gibson, Heike; Suh, Helen H; Coull, Brent A; Dockery, Douglas W; Sarnat, Stefanie Ebelt; Schwartz, Joel; Stone, Peter H; Gold, Diane R

2015-01-01

Objectives Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects. Methods 25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM2.5) and sulphate (SO42−) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status. Results A 5.8 mg/l elevation in CRP was associated with decreases of between −8% and −33% for time and frequency domain HRV outcomes. A 5.1 μg/m3 increase in SO42− on the day before the health assessment was associated with a decrease of −6.7% in the SD of normal RR intervals (SDNN) (95% CI −11.8% to −1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM2.5. Conclusions Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation. PMID:20519749

Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism.

PubMed

Brang, David; Ramachandran, V S

2010-05-01

Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.

The Influence of Epicardial Fat and Nonalcoholic Fatty Liver Disease on Heart Rate Recovery in Metabolic Syndrome.

PubMed

Cho, Kyoung Im; Jo, Eun Ah; Cho, Sang Hoon; Kim, Bo Hyun

2017-06-01

Epicardial adipose tissues reflecting visceral fat accumulations of the heart are associated with metabolic syndrome (MetS) and can be a predictor of other cardiometabolic diseases. It can adversely influence autonomic nervous system (ANS) of heart. Heart rate recovery (HRR) is an easy method for measuring ANS dysfunction. The purpose of this study was to determine whether epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD) are related to HRR in patients with MetS. We enrolled 772 consecutive patients from a health-screening center who underwent abdominal ultrasonography, treadmill test, and cardiac echocardiography. EFT using echocardiography and HRR by symptom-limited exercise testing was assessed. According to the presence of MetS and NAFLD, patients were classified into the four groups. In NAFLD patients, EFT was higher and HRR was lower, especially in patients with MetS and NAFLD, compared to non-MetS participants without NAFLD (MetS with NAFLD, EFT 7.5 ± 4.4 mm, HRR 31.9 ± 12.7; MetS without NAFLD, EFT 4.9 ± 3.0 mm, HRR 39.5 ± 11.1; non-MetS with NAFLD, EFT 5.9 ± 3.6 mm, HRR 36.6 ± 12.7; and non-MetS without NAFLD, EFT 4.4 ± 3.5 mm, HRR 43.4 ± 14.5, p < 0.001). Patients with severe liver steatosis (LS) showed significantly higher EFT than those with moderate LS (14.2 ± 2.0 vs. 7.5 ± 3.1 mm, P < 0.001), and EFT was positively correlated with severity of LS (r = 0.431, P < 0.001). HRR was significantly correlated with EFT (r = -0.386, P < 0.001) and severity of LS (r = -0.324, P < 0.001). EFT and NAFLD were significantly correlated with HRR in patients with MetS and they may be highly related to increased cardiovascular risk. These results suggest a cross-link among EFT, NAFLD, and cardiac autonomic dysfunction in patients with MetS.

Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing

PubMed Central

Li, Mian; Xu, Changqing; Yao, Wenguo; Mahan, Clare M.; Kang, Han K.; Sandbrink, Friedhelm; Zhai, Ping; Karasik, Pamela A.

2014-01-01

To determine if objective evidence of autonomic dysfunction exists from a group of Gulf War veterans with self-reported post-exertional fatigue, we evaluated 16 Gulf War ill veterans and 12 Gulf War controls. Participants of the ill group had self- reported, unexplained chronic post-exertional fatigue and the illness symptoms had persisted for years until the current clinical study. The controls had no self-reported post-exertional fatigue either at the time of initial survey nor at the time of the current study. We intended to identify clinical autonomic disorders using autonomic and neurophysiologic testing in the clinical context. We compared the autonomic measures between the 2 groups on cardiovascular function at both baseline and head-up tilt, and sudomotor function. We identified 1 participant with orthostatic hypotension, 1 posture orthostatic tachycardia syndrome, 2 distal small fiber neuropathy, and 1 length dependent distal neuropathy affecting both large and small fiber in the ill group; whereas none of above definable diagnoses was noted in the controls. The ill group had a significantly higher baseline heart rate compared to controls. Compound autonomic scoring scale showed a significant higher score (95% CI of mean: 1.72–2.67) among ill group compared to controls (0.58–1.59). We conclude that objective autonomic testing is necessary for the evaluation of self-reported, unexplained post-exertional fatigue among some Gulf War veterans with multi-symptom illnesses. Our observation that ill veterans with self-reported post-exertional fatigue had objective autonomic measures that were worse than controls warrants validation in a larger clinical series. PMID:24431987

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

PubMed

Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

2016-08-01

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

Sudden unexpected death in epilepsy.

PubMed

Shorvon, Simon; Tomson, Torbjorn

2011-12-10

Sudden unexpected death in epilepsy (SUDEP) refers to the sudden death of a seemingly healthy individual with epilepsy, usually occurring during, or immediately after, a tonic-clonic seizure. The frequency of SUDEP varies depending on the severity of the epilepsy, but overall the risk of sudden death is more than 20 times higher than that in the general population. Several different mechanisms probably exist, and most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction. Data from a pooled analysis of risk factors indicate that the higher the frequency of tonic-clonic seizures, the higher the risk of SUDEP; furthermore, risk of SUDEP is also elevated in male patients, patients with long-duration epilepsy, and those on antiepileptic polytherapy. SUDEP usually occurs when the seizures are not witnessed and often at night. In this Seminar, we provide advice to clinicians on ways to minimise the risk of SUDEP, information to pass on to patients, and medicolegal aspects of these deaths. Copyright © 2011 Elsevier Ltd. All rights reserved.

Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease.

PubMed

Nelson, Alexander; Otto, James; Whittle, John; Stephens, Robert C M; Martin, Daniel S; Prowle, John R; Ackland, Gareth L

2016-01-01

Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure. Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension. CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)). Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD.

Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

PubMed Central

Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

2015-01-01

Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus.

PubMed

Brinth, Louise S; Pors, Kirsten; Theibel, Ann C; Mehlsen, Jesper

2015-05-21

Infections with human papilloma virus (HPV) can result in cervical, oropharyngeal, anal, and penile cancer and vaccination programs have been launched in many countries as a preventive measure. We report the characteristics of a number of patients with a syndrome of orthostatic intolerance, headache, fatigue, cognitive dysfunction, and neuropathic pain starting in close relation to HPV vaccination. Patients were referred for orthostatic intolerance following HPV vaccination. Symptoms of autonomic dysfunction were quantified by standardised questionnaire. The diagnosis of postural orthostatic tachycardia syndrome (POTS) rested on finding a sustained heart rate increment of >30 min(-1) (>40 min(-1) in adolescents) or to levels >120 min(-1) during orthostatic challenge. 35 women aged 23.3 ± 7.1 years participated. Twenty-five had a high level of physical activity before vaccination and irregular periods were reported by all patients not on treatment with oral contraception. Serum bilirubin was below the lower detection limit in 17 patients. Twenty-one of the referred patients fulfilled the criteria for a diagnosis of POTS (60%, 95%CI 43-77%). All patients had orthostatic intolerance, 94% nausea, 82% chronic headache, 82% fatigue, 77% cognitive dysfunction, 72% segmental dystonia, 68% neuropathic pain. In a population referred for symptoms of orthostatic intolerance and other symptoms consistent with autonomic dysfunction that began in close temporal association with a quadrivalent HPV vaccination, we identified a 60% prevalence of POTS. Further work is urgently needed to elucidate the potential for a causal link between the vaccine and circulatory abnormalities and to establish targeted treatment options for the affected patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Autonomic Evaluation of Patients With Gastroparesis and Neurostimulation: Comparisons of Direct/Systemic and Indirect/Cardiac Measures

PubMed Central

Stocker, Abigail; Abell, Thomas L.; Rashed, Hani; Kedar, Archana; Boatright, Ben; Chen, Jiande

2016-01-01

Background Disorders of nausea, vomiting, abdominal pain, and related problems often are manifestations of gastrointestinal, neuromuscular, and/or autonomic dysfunction. Many of these patients respond to neurostimulation, either gastric electrical stimulation or electroacupuncture. Both of these therapeutic techniques appear to influence the autonomic nervous system which can be evaluated directly by traditional testing and indirectly by heart rate variability. Methods We studied patients undergoing gastric neuromodulation by both systemic autonomic testing (39 patients, six males and 33 females, mean age 38 years) and systemic autonomic testing and heart rate variability (35 patients, seven males and 28 females, mean age 37 years) testing before and after gastric neuromodulation. We also performed a pilot study using both systemic autonomic testing and heart rate variability in a small number of patients (five patients, all females, mean age 48.6 years) with diabetic gastroparesis at baseline to compare the two techniques at baseline. Systemic autonomic testing and heart rate variability were performed with standardized techniques and gastric electrical stimulation was performed as previously described with electrodes implanted serosally in the myenteric plexus. Results Both systemic autonomic testing and heart rate variability measures were often abnormal at baseline and showed changes after gastric neuromodulation therapy in two groups of symptomatic patients. Pilot data on a small group of similar patients with systemic automatic nervous measures and heart rate variability showed good concordance between the two techniques. Conclusions Both traditional direct autonomic measures and indirect measures such as heart rate variability were evaluated, including a pilot study of both methods in the same patient group. Both appear to be useful in evaluation of patients at baseline and after stimulation therapies; however, a future full head-to-head comparison is warranted. PMID:27785318

[Response of pancreatic polypeptide to a protein rich meal in insulin non dependent diabetes melitus and autonomic neuropathy].

PubMed

Kostić, N; Zamaklar, M; Novaković, R; Stajić, S

1994-01-01

Parasympathetic function and plasma hPP response to a protein rich meal were evaluated in 105 insulin non-dependent diabetic patients: 20 with autonomic neuropathy (group A), diagnosed by Clonidin test; 35 patients with neurophysiological evidence of polyneuropath (group B); 30 patients with autonomic neuropathy and polineuropathy (group C), and 20 patients without any sign of neuropathy (group D). Plasma hPP levels were determined by RIA using an anti-hPP antiserum, kindly provided by Prof. S. R. Bloom (Hammersmith Hospital, London). Blood was taken at 0. 45 and 60 minutes after the beginning of the meal. In groups A and C, the meal induced hPP increase was significantly lower than in group D (p 0.001). All group B patients had a marked increase in the peptide, similar to that in diabetics without neuropathy. These result ssuggest that diabetic autonomic neuropathy is associated with dysfunction of hPP secretion, and that the evaluation of hPP response to test meal may be a sensitive and simple method for the assessment of paraympathetic impairment in diabetes.

Guillian-Barré syndrome in high tetraplegia following acute respiratory illness.

PubMed

Grant, C; Briscoe, N; Mezei, M; Krassioukov, A

2011-03-01

A case report of a Guillain-Barré syndrome (GBS) variant presenting in a patient with a high cervical spinal cord injury (SCI). To illustrate a clinical presentation of GBS in an individual with chronic SCI. Vancouver General Hospital, Vancouver, BC, Canada. A 31-year-old man with chronic C2 AIS B (American Spinal Injury Association Impairment Scale) SCI and diaphragmatic pacing presented with respiratory failure with sepsis. His sepsis resolved with antibiotic therapy, but he continued to have autonomic instability and was unable to be weaned off his ventilator. Concurrently he developed flaccidity and facial diplegia. Investigations including nerve conduction studies and cerebrospinal fluid analysis prompted a diagnosis of acute motor-sensory axonal neuropathy, a variant of Guillian-Barré syndrome. Owing to ongoing autonomic instability, he was treated with intravenous immunoglobulin. His autonomic dysfunction resolved and he regained some facial muscle function, but 6 months post injury he remained dysphagic and required 24-h ventilator support. Careful neurological reassessment prompted the diagnosis of acute polyradiculoneuropathy following respiratory sepsis as the root cause of diaphragmatic pacer failure and autonomic instability.

Dysfunctional stress responses in chronic pain.

PubMed

Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Neuro-urological diagnosis and therapy of lower urinary tract dysfunction in patients with spinal cord injury : S2k Guideline of the German-Speaking Medical Society of Paraplegia (DMGP), AWMF register no. 179/001].

PubMed

Böthig, R; Domurath, B; Kaufmann, A; Bremer, J; Vance, W; Kurze, I

2017-06-01

Most patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD), bowel dysfunction and sexual dysfunction. If these remain untreated, severe medical complications and serious limitations (restrictions) in quality of life are imminent. In the long term, there are considerable differences in the treatment results of highly specialized centers versus other treatment facilities. Against this background, a consensus-based guideline, according to the AWMF (Association of the Scientific Medical Societies in Germany) criteria (S2k), was developed by the neuro-urology working group of the DMPG (German-Speaking Medical Society of Paraplegia). The guideline defines the principles and objectives of the neuro-urological care of patients with SCI and discusses in detail the principles of diagnosis and therapy of NLUTD. The need for video-urodynamic studies as a basis for the classification of the NLUTD and as a foundation for the development of a treatment strategy is emphasized. Both conservative and surgical therapy options and their indications are explained in detail. Possible complications and their prevention in the long-term course of SCI are presented with a particular consideration of the specific features of urinary tract infections and autonomic dysreflexia. Finally, the principles of the provision of urological appliances are discussed. The presented S2k guideline provides the current standards in the neuro-urological care of patients with NLUTD due to SCI. Their consistent implementation both in the acute and chronic phase as well as in the context of lifelong surveillance of SCI patients should prevent the impending complications of NLUTD.

Flow in the left anterior descending coronary artery in patients with migraine headache.

PubMed

Aslan, Gamze; Sade, Leyla Elif; Yetis, Begum; Bozbas, Huseyin; Eroglu, Serpil; Pirat, Bahar; Can, Ufuk; Muderrisoglu, Haldun

2013-11-15

Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurologic symptoms. Migraine can affect many systems in the body, yet its effects on cardiovascular system are unclear. We hypothesized that migraine and coronary microvascular angina may be manifestations of a common systemic microvascular dysfunction and clinically associated. Forty patients with migraine and 35 healthy volunteers were included into the study. Using transthoracic Doppler echocardiography, coronary flow was visualized in the middle or distal part of the left anterior descending artery. Coronary diastolic peak flow velocities were measured with pulse wave Doppler at baseline and after dipyridamole infusion (0.56 mg/kg/4 min). Coronary flow reserve of <2 was considered normal. In addition, thorough 2-dimensional and Doppler echocardiographic examinations were also performed. Fifty-two women and 23 men were included. Coronary flow reserve was significantly lesser in the migraine group than in the control group (1.99 ± 0.3 vs 2.90 ± 0.5, p <0.05). In addition, mitral annular velocities were lower and the ratio of early mitral inflow velocity to early mitral annular velocity (E/E' lateral and E/E' septal) was higher in migraineurs than in the control group (p <0.05 for all), indicating diastolic function abnormalities in the migraine group. In conclusion, these findings suggest that there is an association between coronary microvascular dysfunction and migraine independently of the metabolic state of the patients. A common pathophysiologic pathway of impaired endothelial vasodilatation, vasomotor dysfunction, and increased systemic inflammatory factors may play a role in these 2 clinical conditions and could be the underlying cause of subclinical systolic and diastolic left ventricular dysfunction in migraineurs. Copyright © 2013 Elsevier Inc. All rights reserved.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness.

PubMed

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A C; de Man, Frances S

2016-07-01

The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. © 2016 The Authors.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

2016-01-01

Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

PubMed

Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H

2012-09-01

Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

PubMed Central

Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

2016-01-01

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

PubMed

Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

2012-06-20

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

The Neurophysiology of Autonomic Dysfunction in SCI: Plasticity in the Input and Output Neurons

DTIC Science & Technology

2014-04-01

multi-segmental spinal pain reflex Location: Halls B-H Presentation Time: Tuesday , Nov 16, 2010, 8:00 AM - 9:00 AM Authors: *K. E. TANSEY1, M...neurological scoring methods. Cognitive functions were tested using Fear Conditioning tests at 8–10 days post- injury and Morris Water Maze tests 11–15

Sweat testing to evaluate autonomic function

PubMed Central

Illigens, Ben M.W.; Gibbons, Christopher H.

2011-01-01

Sudomotor dysfunction is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), and the recent addition of quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localized pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we review the common tests available for assessment of sudomotor function, detail the testing methodology, review the limitations and provide examples of test results. PMID:18989618

Subclinical hyperthyroidism and sudden unexpected death in epilepsy.

PubMed

Scorza, Fulvio A; Arida, Ricardo M; Cysneiros, Roberta M; Terra, Vera C; de Albuquerque, Marly; Machado, Hélio R; Cavalheiro, Esper A

2010-04-01

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, several studies have shown a link between hormones and epilepsy. However, exact knowledge regarding the association of thyroid hormones and epilepsy is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease, we propose in this paper that SUDEP, at least in some cases, could be related with subclinical thyroid dysfunction. (c) 2009 Elsevier Ltd. All rights reserved.

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.

PubMed

Gamboa, Alfredo; Figueroa, Rocío; Paranjape, Sachin Y; Farley, Ginnie; Diedrich, Andre; Biaggioni, Italo

2016-10-01

Impaired nitric oxide (NO) vasodilation (endothelial dysfunction) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30

Autonomic Nervous System and Stress to Predict Secondary Ischemic Events after Transient Ischemic Attack or Minor Stroke: Possible Implications of Heart Rate Variability.

PubMed

Guan, Ling; Collet, Jean-Paul; Mazowita, Garey; Claydon, Victoria E

2018-01-01

Transient ischemic attack (TIA) and minor stroke have high risks of recurrence and deterioration into severe ischemic strokes. Risk stratification of TIA and minor stroke is essential for early effective treatment. Traditional tools have only moderate predictive value, likely due to their inclusion of the limited number of stroke risk factors. Our review follows Hans Selye's fundamental work on stress theory and the progressive shift of the autonomic nervous system (ANS) from adaptation to disease when stress becomes chronic. We will first show that traditional risk factors and acute triggers of ischemic stroke are chronic and acute stress factors or "stressors," respectively. Our first review shows solid evidence of the relationship between chronic stress and stroke occurrence. The stress response is tightly regulated by the ANS whose function can be assessed with heart rate variability (HRV). Our second review demonstrates that stress-related risk factors of ischemic stroke are correlated with ANS dysfunction and impaired HRV. Our conclusions support the idea that HRV parameters may represent the combined effects of all body stressors that are risk factors for ischemic stroke and, thus, may be of important predictive value for the risk of subsequent ischemic events after TIA or minor stroke.

Autonomic Nervous System and Stress to Predict Secondary Ischemic Events after Transient Ischemic Attack or Minor Stroke: Possible Implications of Heart Rate Variability

PubMed Central

Guan, Ling; Collet, Jean-Paul; Mazowita, Garey; Claydon, Victoria E.

2018-01-01

Transient ischemic attack (TIA) and minor stroke have high risks of recurrence and deterioration into severe ischemic strokes. Risk stratification of TIA and minor stroke is essential for early effective treatment. Traditional tools have only moderate predictive value, likely due to their inclusion of the limited number of stroke risk factors. Our review follows Hans Selye’s fundamental work on stress theory and the progressive shift of the autonomic nervous system (ANS) from adaptation to disease when stress becomes chronic. We will first show that traditional risk factors and acute triggers of ischemic stroke are chronic and acute stress factors or “stressors,” respectively. Our first review shows solid evidence of the relationship between chronic stress and stroke occurrence. The stress response is tightly regulated by the ANS whose function can be assessed with heart rate variability (HRV). Our second review demonstrates that stress-related risk factors of ischemic stroke are correlated with ANS dysfunction and impaired HRV. Our conclusions support the idea that HRV parameters may represent the combined effects of all body stressors that are risk factors for ischemic stroke and, thus, may be of important predictive value for the risk of subsequent ischemic events after TIA or minor stroke. PMID:29556209

[Сhanges in heart rate variability in presymptomatic and symptomatic stages of Parkinson's disease under pharmacological influences: an experimental study].

PubMed

Mamalyga, M L

2013-01-01

The disbalance of autonomic heart regulation (AHR) develops already in the presymptomatic stage of Parkinson's disease. The early symptomatic stage is accompanied by the aggravation of heart dysfunction due to the shift of the autonomic balance towards the increase of sympathetic and decrease of parasympathic effect on the heart. Coronary disorders concomitant to Parkinson's disease increase a risk of life threatening arrhythmia and sudden death syndrome not only in the early symptomatic stage but also in the presymptomatic stage. L-DOPA effectively restores the structure of AHR and prevents the risk of life threatening arrhythmia only in the presymptomatic stage of Parkinson's disease.

Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats.

PubMed

Marques-Neto, Silvio Rodrigues; Castiglione, Raquel Carvalho; Pontes, Aiza; Oliveira, Dahienne Ferreira; Ferraz, Emanuelle Baptista; Nascimento, José Hamilton Matheus; Bouskela, Eliete

2016-01-01

Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats. We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet. Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

PubMed

Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-01-01

To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

Pupillary autonomic denervation with increasing duration of diabetes mellitus

PubMed Central

Cahill, M.; Eustace, P.; de Jesus, V.

2001-01-01

BACKGROUND/AIMS—The autonomic pupillary changes in type I and II diabetic patients without clinical evidence of diabetic autonomic neuropathy (DAN) were compared with age matched controls. The relation between pupillary and cardiovascular autonomic function was assessed in the diabetic patients.
METHODS—A case-control study was performed with diabetics grouped according to type and duration of diabetes. Static infrared pupillography was used to compare mean dark adapted pupil size and mean percentage changes in pupil size with pilocarpine 0.1% and cocaine 4% in the diabetic and control groups. All diabetic patients underwent cardiovascular autonomic function assessment using the Valsalva ratio, the 30:15 ratio, and testing for orthostatic hypotension.
RESULTS—In total, 72 type I and 69 type II diabetic patients were compared with 120 controls. Mean dark adapted pupil size was significantly smaller in diabetic groups than controls. Except for type I diabetics with disease for less than 5 years, all patient groups had significantly greater mean percentage constriction in pupil size in response to dilute pilocarpine than controls. There was no significant difference between the mean percentage dilatation in response to cocaine 4% in diabetics and controls. A high proportion of patients had normal cardiovascular autonomic function particularly when this was assessed with the Valsalva ratio.
CONCLUSIONS—Denervation hypersensitivity to dilute pilocarpine is a result of damage to the pupillary parasympathetic supply of diabetic patients. This occurs before the pupillary sympathetic pathway is affected, it can be detected early in the disease, and it may be a possible explanation for the small pupil size seen in diabetic patients. Pupillary autonomic dysfunction occurs before cardiovascular autonomic changes and detection of pupil denervation hypersensitivity to dilute pilocarpine is an inexpensive way to detect early DAN.

 PMID:11567969

Benign Joint Hypermobility Minimally Impacts Autonomic Abnormalities in Pediatric Subjects with Chronic Functional Pain Disorders.

PubMed

Chelimsky, Gisela; Kovacic, Katja; Simpson, Pippa; Nugent, Melodee; Basel, Donald; Banda, Julie; Chelimsky, Thomas

2016-10-01

To determine if children with benign joint hypermobility (BJH) syndrome and chronic functional pain disorders have more autonomic dysfunction. Retrospective chart review study of pediatric patients seen in the pediatric neurogastroenterology and autonomic clinic who underwent autonomic testing and had either a Beighton score of ≥6 and met Brighton criteria for BJH (with BJH) or a score of ≤2 (no BJH). Twenty-one female subjects (10 without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by genetics consultation. We evaluated for postural tachycardia syndrome, syncope, orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as well as baseline heart rate, peak heart rate in first 10 minutes of head up tilt (P = .35 and P = .61, respectively), and sudomotor index (suggestive of autonomic neuropathy) (P = .58), showed differences between the groups. Age of onset of symptoms was also similar (P = .61) (BJH vs without BJH: median [range]:15.6 years [12.9-17.5] vs 15.4 years [11.1-18.2]). There was no difference between groups in complaints of migraine, chronic nausea, chronic fatigue, lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep, irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal pain, constipation, or fibromyalgia. Children with chronic functional pain disorders and BJH have autonomic testing findings and comorbid features compared with a similar cohort of subjects without BJH, suggesting that BJH is not the driver of the autonomic and comorbid disorders. Copyright © 2016. Published by Elsevier Inc.

Cardiac abnormalities in Parkinson's disease and Parkinsonism.

PubMed

Scorza, Fulvio A; Fiorini, Ana C; Scorza, Carla A; Finsterer, Josef

2018-07-01

Though there is increasing evidence for primary cardiac disease in Parkinson's disease (PD) and Parkinsonism (PS), this evidence is hardly included in the general management of these patients. Literature review. PD is one of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that PD is accompanied by high rates of premature death compared with the general population. In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS. Cardiac involvement in PD/PS includes cardiac autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmias, conduction defects, and sudden cardiac death (SCD), and sudden unexpected death in Parkinson's disease (SUDPAR). Cardiac abnormalities found in PD/PS are manifold but the most prominent is cardiac autonomic dysfunction. The frequency of coronary heart disease in PD is a matter of debate. Only rarely reported in PD/PS are cardiomyopathies, arrhythmias, and sudden cardiac death, and SUDPAR. It is particularly recommended that PD/PS patients are more intensively investigated cardiologically as soon as the diagnosis is established. Early recognition of cardiac involvement is important for preventing SCD and SUDPAR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dysfunctional penile cholinergic nerves in diabetic impotent men

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanco, R.; Saenz de Tejada, I.; Goldstein, I.

1990-08-01

Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to thatmore » from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.« less

[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].

PubMed

Watanabe, Masashi; Matsumoto, Yushi; Okamoto, Kensho; Okuda, Bungo; Mizuta, Ikuko; Mizuno, Toshiki

2017-12-27

A 49-year-old man had developed gradually personality change, gait disturbance, and hearing loss for five years. On admission, he presented with frontal release signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity, ataxia, and sensory disturbance with areflexia in the lower extremities. Brain MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed as progressive supranuclear palsy on the basis of clinical features and imagings. On nerve conduction study, no sensory nerve action potentials were elicited in the upper and lower extremities. Details of family history revealed a hereditary sensory neuropathy with autosomal dominant inheritance in his relatives. Because genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene, we diagnosed him as having hereditary sensory and autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion protein gene was detected. It should be kept in mind that there are some patients with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and with clinical features mimicking progressive supranuclear palsy.

Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm disorder.

PubMed

Tanaka, Masaaki; Tajima, Seiki; Mizuno, Kei; Ishii, Akira; Konishi, Yukuo; Miike, Teruhisa; Watanabe, Yasuyoshi

2015-11-01

Fatigue is defined as a condition or phenomenon of decreased ability and efficiency of mental and/or physical activities, caused by excessive mental or physical activities, diseases, or syndromes. It is often accompanied by a peculiar sense of discomfort, a desire to rest, and reduced motivation, referred to as fatigue sensation. Acute fatigue is a normal condition or phenomenon that disappears after a period of rest; in contrast, chronic fatigue, lasting at least 6 months, does not disappear after ordinary rest. Chronic fatigue impairs activities and contributes to various medical conditions, such as cardiovascular disease, epileptic seizures, and death. In addition, many people complain of chronic fatigue. For example, in Japan, more than one third of the general adult population complains of chronic fatigue. It would thus be of great value to clarify the mechanisms underlying chronic fatigue and to develop efficient treatment methods to overcome it. Here, we review data primarily from behavioral, electrophysiological, and neuroimaging experiments related to neural dysfunction as well as autonomic nervous system, sleep, and circadian rhythm disorders in fatigue. These data provide new perspectives on the mechanisms underlying chronic fatigue and on overcoming it.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress.

PubMed

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress.

Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I.

PubMed

Cohen, H E; Hall, J; Harris, N; McCabe, C S; Blake, D R; Jänig, W

2012-02-01

Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub-group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways. © 2011 European Federation of International Association for the Study of Pain Chapters.

Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

PubMed Central

Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

2014-01-01

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction

PubMed Central

Hermann, Gerlinda E.; Van Meter, Montina J.; Rogers, Richard C.

2014-01-01

The chemokine receptor, CXCR4, plays an essential role in guiding neural development of the CNS. Its natural agonist, CXCL12 [or stromal cell-derived factor-1 (SDF-1)], normally is derived from stromal cells, but is also produced by damaged and virus-infected neurons and glia. Pathologically, this receptor is critical to the proliferation of the HIV virus and initiation of metastatic cell growth in the brain. Anorexia, nausea and failed autonomic regulation of gastrointestinal (GI) function cause morbidity and contribute to the mortality associated with these disease states. Our previous work on the peripheral cytokine, tumor necrosis factor-alpha, demonstrated that similar morbidity factors involving GI dysfunction are attributable to agonist action on neural circuit elements of the dorsal vagal complex (DVC) of the hindbrain. The DVC includes vagal afferent terminations in the solitary nucleus, neurons in the solitary nucleus (NST) and area postrema, and visceral efferent motor neurons in the dorsal motor nucleus (DMN) that are responsible for the neural regulation of digestive functions from the oral cavity to the transverse colon. Immunohistochemical techniques demonstrate a dense concentration of CXCR4 receptors on neurons throughout the DVC and the hypoglossal nucleus. CXCR4-immunoreactivity is also intense on microglia within the DVC, though not on the astrocytes. Physiological studies show that nanoinjection of SDF-1 into the DVC produces a significant reduction in gastric motility in parallel with an elevation in the numbers of cFOS-activated neurons in the NST and DMN. These results suggest that this chemokine receptor may contribute to autonomically mediated pathophysiological events associated with CNS metastasis and infection. PMID:18333961

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

PubMed

Ward, Christopher S; Huang, Teng-Wei; Herrera, José A; Samaco, Rodney C; Pitcher, Meagan R; Herron, Alan; Skinner, Steven A; Kaufmann, Walter E; Glaze, Daniel G; Percy, Alan K; Neul, Jeffrey L

2016-01-01

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome

PubMed Central

Ward, Christopher S.; Huang, Teng-Wei; Herrera, José A.; Samaco, Rodney C.; Pitcher, Meagan R.; Herron, Alan; Skinner, Steven A.; Kaufmann, Walter E.; Glaze, Daniel G.; Percy, Alan K.; Neul, Jeffrey L.

2016-01-01

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized. PMID:27828991

Autonomic dysfunction and osteoporosis after electrical burn.

PubMed

Roshanzamir, Sharareh; Dabbaghmanesh, Mohammad Hossein; Dabbaghmanesh, Alireza; Nejati, Solmaz

2016-05-01

Several studies have shown the importance of the sympathetic nervous system in bone metabolism. There is an evidence of sympathetic skin response (SSR) impairment in electrical burn patients up to 2 years after their injuries. The acute phase of burn is accompanied by increased bone resorption. Whether the prolonged dysfunction of sympathetic nervous system may result in bone metabolism derangement even after the acute phase of electrical burn is the inspiring question for this study. And we tried to find correlation between SSR abnormality and areal bone mineral density (BMD) in electrical burn patients 6 months or more after the incidents. 42 electrical burn patients (≥6 months prior to study) who did not have a known joint or bone disease, history of neuropathy (central or peripheral), diabetes mellitus or consumption of any drug affecting the autonomic nervous system or evidence of neuropathy in nerve conduction study were recruited. We also gathered a control group of 50 healthy subjects (without electrical burn or the exclusion criteria). They went under dual energy X-ray absorptiometry and SSR study. Data were analyzed statistically with SPSS 16.0 making use of independent t-test and Pearson correlation coefficient. P<0.05 was considered significant statistically. Areal BMD was significantly lower in electrical burn patients than control group (P<0.001). SSR latency was significantly prolonged and its amplitude was significantly reduced in burn patients compared to control group (P<0.001). In burn patients there was an inverse correlation of areal BMD of lumbar vertebrae, left femur neck and total femur with SSR latency and a direct correlation of areal BMD with SSR amplitude. In control group there was just direct correlation of areal BMD of lumbar vertebrae and left femur neck with SSR amplitude. Electrical burn patients are at risk of reduced areal BMD long after their injuries. Sympathetic derangement and impaired SSR are correlated with reduction in areal BMD in these patients. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Non-motor symptoms in Parkinson's disease.

PubMed

Poewe, W

2008-04-01

Although still considered a paradigmatic movement disorder, Parkinson's disease (PD) is associated with a broad spectrum of non-motor symptoms. These include disorders of mood and affect with apathy, anhedonia and depression, cognitive dysfunction and hallucinosis, as well as complex behavioural disorders. Sensory dysfunction with hyposmia or pain is almost universal, as are disturbances of sleep-wake cycle regulation. Autonomic dysfunction including orthostatic hypotension, urogenital dysfunction and constipation is also present to some degree in a majority of patients. Whilst overall non-motor symptoms become increasingly prevalent with advancing disease, many of them can also antedate the first occurrence of motor signs - most notably depression, hyposmia or rapid eye movement sleep behaviour disorder (RBD). Although exact clinicopathological correlations for most of these non-motor features are still poorly understood, the occurrence of constipation, RBD or hyposmia prior to the onset of clinically overt motor dysfunction would appear consistent with the ascending hypothesis of PD pathology proposed by Braak and colleagues. Screening these early non-motor features might, therefore, be one approach towards early 'preclinical' diagnosis of PD. This review article provides an overview of the clinical spectrum of non-motor symptoms in PD together with a brief review of treatment options.

Autonomic nervous function in patients with Meniere's disease evaluated by power spectral analysis of heart rate variability.

PubMed

Yamada, M; Mizuta, K; Ito, Y; Furuta, M; Sawai, S; Miyata, H

1999-10-01

A hypothesis has been advanced that the autonomic nervous dysfunction (AND) relates to the development of vertigo in Meniere's disease (MD). We also studied the causal relationship between AND and vertigo in MD. We evaluated autonomic nervous function in 17 patients with MD (five men and 12 women ranging in age from 16 to 70 years) by classifying them by their stages of attack and interval of vertigo and with power spectral analysis (PSA) of heart rate variability. Fourteen healthy volunteers were also tested as controls. At the interval stage, parasympathetic nervous hypofunction and significant depression of sympathetic response due to postural changes from the supine to the standing position were observed in many of those patients. At the attack stage, sympathetic nervous hypofunction was observed in some of the patients. These findings lead us to the conclusion that AND relates to vertigo in MD as a predisposing factor. However, the question of whether AND relates as a trigger or as a consequence of vertigo in MD has not been adequately solved in this study. We will make further studies on circadian variation of autonomic nervous function.

Female Mecp2+/− mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies

PubMed Central

Samaco, Rodney C.; McGraw, Christopher M.; Ward, Christopher S.; Sun, Yaling; Neul, Jeffrey L.; Zoghbi, Huda Y.

2013-01-01

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the gene encoding the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2). Typical RTT primarily affects girls and is characterized by a brief period of apparently normal development followed by the loss of purposeful hand skills and language, the onset of anxiety, hand stereotypies, autistic features, seizures and autonomic dysfunction. Mecp2 mouse models have extensively been studied to demonstrate the functional link between MeCP2 dysfunction and RTT pathogenesis. However, the majority of studies have focused primarily on the molecular and behavioral consequences of the complete absence of MeCP2 in male mice. Studies of female Mecp2+/− mice have been limited because of potential phenotypic variability due to X chromosome inactivation effects. To determine whether reproducible and reliable phenotypes can be detected Mecp2+/− mice, we analyzed Mecp2+/− mice of two different F1 hybrid isogenic backgrounds and at young and old ages using several neurobehavioral and physiological assays. Here, we report a multitude of phenotypes in female Mecp2+/− mice, some presenting as early as 5 weeks of life. We demonstrate that Mecp2+/− mice recapitulate several aspects of typical RTT and show that mosaic expression of MeCP2 does not preclude the use of female mice in behavioral and molecular studies. Importantly, we uncover several behavioral abnormalities that are present in two genetic backgrounds and report on phenotypes that are unique to one background. These findings provide a framework for pre-clinical studies aimed at improving the constellation of phenotypes in a mouse model of RTT. PMID:23026749

[Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors].

PubMed

Márquez, Manlio F; Gómez-Flores, Jorge Rafael; González-Hermosillo, Jesús A; Ruíz-Siller, Teresita de Jesús; Cárdenas, Manuel

2016-12-29

Vasovagal or neurocardiogenic syncope is a common clinical situation and, as with other entities associated with orthostatic intolerance, the underlying condition is a dysfunction of the autonomic nervous system. This article reviews various aspects of vasovagal syncope, including its relationship with orthostatic intolerance and the role of the autonomic nervous system in it. A brief history of the problem is given, as well as a description of how the names and associated concepts have evolved. The response of the sympathetic system to orthostatic stress, the physiology of the baroreflex system and the neurohumoral changes that occur with standing are analyzed. Evidence is presented of the involvement of the autonomic nervous system, including studies of heart rate variability, microneurography, cardiac innervation, and molecular genetic studies. Finally, we describe different studies on the use of beta-blockers and norepinephrine transporter inhibitors (sibutramine, reboxetine) and the rationality of their use to prevent this type of syncope. Creative Commons

[Using autonomous electrostimulation device Erektron in treating female overactive bladder].

PubMed

Yarin, G Yu; Shelyakina, O V; Fedorenko, V N; Alekseeva, A V; Vilgelmi, I A

2016-11-01

Overactive bladder (OAB) is one of the most common syndromes of lower urinary tract dysfunction. Besides standard therapy using anticholinergic medications, comprehensive management of overactive bladder includes physiotherapy. To test the clinical effectiveness and safety of autonomous electrostimulation device "Erektron" in treating OAB in women. The study was conducted at the Urology and Gynecology Clinic of the Innovative Medical Technology Center between 25.04.2014 and 30.01.2015. It included 20 women with newly diagnosed OAB both with and without urinary urgency incontinence or urinary stress incontinence. The patients were divided into 2 groups. All patients were treated with the first line anticholinergic agent solifenacin 5 mg daily. In patients of group 1, anticholinergic therapy was administered concurrently with intravaginal electrostimulation using "Erektron" device. In both groups, the treatment resulted in positive results, but a more pronounced improvement was found in group 1 patients with mixed incontinence. Autonomous electrostimulation device MT-RV "Erektron" can be used in comprehensive management of patients with OAB, including those with stress urinary incontinence.

Inhalation of 7.5% carbon dioxide increases threat processing in humans.

PubMed

Garner, Matthew; Attwood, Angela; Baldwin, David S; James, Alexandra; Munafò, Marcus R

2011-07-01

Inhalation of 7.5% CO(2) increases anxiety and autonomic arousal in humans, and elicits fear behavior in animals. However, it is not known whether CO(2) challenge in humans induces dysfunction in neurocognitive processes that characterize generalized anxiety, notably selective attention to environmental threat. Healthy volunteers completed an emotional antisaccade task in which they looked toward or away from (inhibited) negative and neutral stimuli during inhalation of 7.5% CO(2) and air. CO(2) inhalation increased anxiety, autonomic arousal, and erroneous eye movements toward threat on antisaccade trials. Autonomic response to CO(2) correlated with hypervigilance to threat (speed to initiate prosaccades) and reduced threat inhibition (increased orienting toward and slower orienting away from threat on antisaccade trials) independent of change in mood. Findings extend evidence that CO(2) triggers fear behavior in animals via direct innervation of a distributed fear network that mobilizes the detection of and allocation of processing resources toward environmental threat in humans.

Direct and Indirect Effects of PM on the Cardiovascular System

PubMed Central

Nelin, Timothy D.; Joseph, Allan M.; Gorr, Matthew W.; Wold, Loren E.

2011-01-01

Human exposure to particulate matter (PM) elicits a variety of responses on the cardiovascular system through both direct and indirect pathways. Indirect effects of PM on the cardiovascular system are mediated through the autonomic nervous system, which controls heart rate variability, and inflammatory responses, which augment acute cardiovascular events and atherosclerosis. Recent research demonstrates that PM also affects the cardiovascular system directly by entry into the systemic circulation. This process causes myocardial dysfunction through mechanisms of reactive oxygen species production, calcium ion interference, and vascular dysfunction. In this review, we will present key evidence in both the direct and indirect pathways, suggest clinical applications of the current literature, and recommend directions for future research. PMID:22119171

Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome.

PubMed

Skrapari, Ioanna; Tentolouris, Nicholas; Katsilambros, Nicholas

2006-08-01

Arterial baroreceptors play an important role in the short-term regulation of arterial pressure, by reflex chronotropic effect on the heart and by reflex regulation of sympathetic outflow. Baroreflex sensitivity (BRS) represents an index of arterial baroreceptors function. Several methods of measuring BRS are available nowadays. Different factors influence BRS in the healthy population, including sex, age, blood pressure, heart rate, body fatness, arterial stiffness, blood glucose and insulin levels, as well as physical activity. Baroreceptors dysfunction is evident in diseases such as coronary artery disease, heart failure, arterial hypertension, diabetes mellitus and obesity. The underlying mechanism of BRS attenuation in diabetes or obesity is not yet well known; however, there is increasing evidence that it is at least partly related to autonomic nervous system dysfunction and particularly to sympathetic overactivity that accompanies these diseases. Blunted BRS provides prognostic information for cardiovascular diseases and possibly for diabetes, while its' prognostic information for obesity is not yet established. This review deals with the mechanisms affecting baroreflex function, the newer techniques of BRS estimation and the most recent insights of baroreflex function in the healthy population and in various diseases with emphasis on diabetes and obesity. In addition, the clinical implication of a reduced BRS in these disorders is discussed.

Central insulin and leptin-mediated autonomic control of glucose homeostasis

PubMed Central

Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

2016-01-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. PMID:21489811

Central insulin and leptin-mediated autonomic control of glucose homeostasis.

PubMed

Marino, Joseph S; Xu, Yong; Hill, Jennifer W

2011-07-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diabetic cardiomyopathy: Where are we 40 years later?

PubMed Central

Sharma, Vijay; McNeill, John H

2006-01-01

Diabetic cardiomyopathy is a cardiac disease that arises as a result of the diabetic state, independent of vascular or valvular pathology. It manifests initially as asymptomatic diastolic dysfunction, which progresses to symptomatic heart failure. The compliance of the heart wall is decreased and contractile function is impaired. The pathophysiology is incompletely understood, but appears to be initiated both by hyperglycemia and changes in cardiac metabolism. These changes induce oxidative stress and activate a number of secondary messenger pathways, leading to cardiac hypertrophy, fibrosis and cell death. Alterations in contractile proteins and intracellular ions impair excitation-contraction coupling, while decreased autonomic responsiveness and autonomic neuropathy impair its regulation. Extensive structural abnormalities also occur, which have deleterious mechanical and functional consequences. PMID:16568154

Hydroalcoholic extract from Nerium oleander L. (Apocynaceae) elicits arrhythmogenic activity.

PubMed

Botelho, Ana Flávia Machado; Santos-Miranda, Artur; Joca, Humberto Cavalcante; Mattoso, Cláudio Roberto Scabelo; de Oliveira, Maira Souza; Pierezan, Felipe; Cruz, Jader Santos; Soto-Blanco, Benito; Melo, Marília Martins

2017-07-12

Nerium oleander L. (OLE) has been used medicinally and is reported to possess a wide range of pharmacological activities. OLE effects are caused by different cardiac glycosides (CG), primarily oleandrin, found within the plant. CG can potentially impair sodium-potassium ATPase (NKA) pump activity and cause positive inotropic effects on the heart. The aim of this study was to investigate the potential arrhythmogenic effects of hydroalcoholic extracts from N. oleander (OLE). OLE hydroalcoholic extracts were obtained from N. oleander leaves and analyzed by HPLC. In vivo experiments with guinea pigs consisted if oral administration of water, 150mg/kg and 300mg/kg OLE extract. Clinical signs and ECG analysis were evaluated. Sample tissues from the heart were processed for histopathological and ultra-structural analysis. Autonomic effects were assessed through pharmacological blockade and ECG monitoring. In vitro experiments were conducted with isolated ventricular myocytes from adult mice. The effects of OLE extract on cardiac excitability, Na + /K + pump current and global Ca 2+ transients were evaluated. Our results demonstrated that OLE hydroalcoholic extract elicited severe cardiac arrhythmias that can lead to death with minimal tissue damage. In vitro experiments suggest that OLE causes electromechanical disturbances in the heart due to inhibition of Na + /K + pump, mitochondrial swelling, and modulation of the sarco(endo)plasmic Ca 2+ ATPase without interfering with the autonomic nervous system. Thus, arrhythmias and electrical conduction disturbances promoted by OLE are mainly associated with impaired cardiomyocyte dysfunction, rather than anatomical tissue remodeling and/or autonomic modulation. Our data revealed the potential cardiotoxicity and positive inotropic effect of OLE and its important role in modulation of electrophysiology in cardiomyocytes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Current and Novel Therapeutic Options for Irritable Bowel Syndrome Management

PubMed Central

Camilleri, Michael; Andresen, Viola

2009-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterized by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of IBS is multifactorial involving disturbances of the brain-gut-axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, α-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride-channel activators, guanylate-cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed. PMID:19665953

Opioids in Pregnancy and Neonatal Abstinence Syndrome

PubMed Central

Stover, Megan W.; Davis, Jonathan M.

2015-01-01

Opiate use in pregnancy has increased dramatically over the past decade and now represents a major public health problem. More women are using prescription opioids, illegal opioids, and opioid substitution therapy. These drugs are associated with numerous obstetrical complications including intrauterine growth restriction, placental abruption, preterm delivery, oligohydramnios, stillbirth, and maternal death. Neonatal complications are also significant, such as an increased risk of mortality as well as neonatal abstinence syndrome (NAS). NAS is a serious and highly variable condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the management of opiate dependence in pregnancy and care of the neonate with prenatal opiate exposure. Since genetic factors appear to be associated with the incidence and severity of NAS, opportunities for “personalized genomic medicine” and unique therapeutic interventions could be developed in the future. PMID:26452318

QUAD fever: beware of non-infectious fever in high spinal cord injuries.

PubMed

Goyal, Jyoti; Jha, Rakesh; Bhatia, Paramjeet; Mani, Raj Kumar

2017-06-18

A case of cervical spinal cord injury and quadriparesis with prolonged fever is being described. Initially, the patient received treatment for well-documented catheter-related bloodstream infection. High spiking fever returned and persisted with no obvious evidence of infection. The usual non-infectious causes too were carefully excluded. QUAD fever or fever due to spinal cord injury itself was considered. The pathogenetic basis of QUAD fever is unclear but could be attributed to autonomic dysfunction and temperature dysregulation. Awareness of this little known condition could help in avoiding unnecessary antimicrobial therapy and in more accurate prognostication. Unlike several previous reported cases that ended fatally, the present case ran a relatively benign course. The spectrum of presentations may therefore be broader than hitherto appreciated. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Slow transit constipation: a review of a colonic functional disorder.

PubMed

Frattini, Jared C; Nogueras, Juan J

2008-05-01

Constipation is a common gastrointestinal complaint that can cause significant physical and psychosocial problems. It has been categorized as slow transit constipation, normal transit constipation, and obstructed defecation. Both the definition and pathophysiology of constipation are unclear, but attempts to describe each of the three types have been made. Slow transit constipation, a functional colonic disorder represents approximately 15 to 30% of constipated patients. The theorized etiologies are disorders of the autonomic and enteric nervous system and/or a dysfunctional neuroendocrine system. Slow transit constipation can be diagnosed with a complete history, physical exam, and a battery of specific diagnostic studies. Once the diagnosis is affirmed and medical management has failed, there are several treatment options. Biofeedback, sacral nerve stimulation, segmental colectomy, and subtotal colectomy with various anastomoses have all been used. Of those treatment options, a subtotal colectomy with ileorectal anastomosis is the most efficacious with the data to support its use.

Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients.

PubMed

Watanabe, Hirohisa; Saito, Yufuko; Terao, Shinichi; Ando, Tetsuo; Kachi, Teruhiko; Mukai, Eiichiro; Aiba, Ikuko; Abe, Yuji; Tamakoshi, Akiko; Doyu, Manabu; Hirayama, Masaaki; Sobue, Gen

2002-05-01

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.

Bladder dysfunction in multiple sclerosis: a 6-year follow-up study.

PubMed

Kisic Tepavcevic, Darija; Pekmezovic, Tatjana; Dujmovic Basuroski, Irena; Mesaros, Sarlota; Drulovic, Jelena

2017-03-01

Bladder dysfunction (BD) is the most common autonomic disturbance in multiple sclerosis, but often overlooked and undertreated. The purpose of this longitudinal study was to explore the changes in the frequency of BD symptoms in MS cohort after a period of 3 and 6 years of follow-up, as well as to investigate the correlations between the presence of BD symptoms and both clinical characteristics and the health-related quality of life (HRQoL) at each subsequent point of estimation. The study population comprises a cohort of 93 patients with MS (McDonald's criteria, 2001). At each time point (baseline, and at the 3- and 6-year follow-up) of estimation, Expanded Disability Status Scale, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Szasz Sexual Functioning Scale and HRQoL (measured by MSQoL-54) were assessed. The proportion of patients with at least one symptom of BD significantly increased over time, for both men and women (from 48.1% at baseline to 51.9% after 3 years and to 71.4% after 6 years of follow-up for males and from 45.5% at baseline to 50.0% after 3 years and to 66.7% after 6 years of follow-up for females). The most common BD problem was urgency of urination. The presence of BD was statistically significantly associated with higher level of physical disability, sexual dysfunction and HRQoL at each point of follow-up, for both men and women. Our results suggested outstanding frequency of BD in patients with MS, with increasing tendency over time.

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?

PubMed

Bellinger, Denise L; Lorton, Dianne

2018-04-13

Immune-Mediated Inflammatory Diseases (IMIDs) is a descriptive term coined for an eclectic group of diseases or conditions that share common inflammatory pathways, and for which there is no definitive etiology. IMIDs affect the elderly most severely, with many older individuals having two or more IMIDs. These diseases include, but are not limited to, type-1 diabetes, obesity, hypertension, chronic pulmonary disease, coronary heart disease, inflammatory bowel disease, and autoimmunity, such as rheumatoid arthritis (RA), Sjőgren's syndrome, systemic lupus erythematosus, psoriasis, psoriatic arthritis, and multiple sclerosis. These diseases are ostensibly unrelated mechanistically, but increase in frequency with age and share chronic systemic inflammation, implicating major roles for the spleen. Chronic systemic and regional inflammation underlies the disease manifestations of IMIDs. Regional inflammation and immune dysfunction promotes targeted end organ tissue damage, whereas systemic inflammation increases morbidity and mortality by affecting multiple organ systems. Chronic inflammation and skewed dysregulated cell-mediated immune responses drive many of these age-related medical disorders. IMIDs are commonly autoimmune-mediated or suspected to be autoimmune diseases. Another shared feature is dysregulation of the autonomic nervous system and hypothalamic pituitary adrenal (HPA) axis. Here, we focus on dysautonomia. In many IMIDs, dysautonomia manifests as an imbalance in activity/reactivity of the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). These major autonomic pathways are essential for allostasis of the immune system, and regulating inflammatory processes and innate and adaptive immunity. Pathology in ANS is a hallmark and causal feature of all IMIDs. Chronic systemic inflammation comorbid with stress pathway dysregulation implicate neural-immune cross-talk in the etiology and pathophysiology of IMIDs. Using a rodent model of inflammatory arthritis as an IMID model, we report disease-specific maladaptive changes in β₂-adrenergic receptor (AR) signaling from protein kinase A (PKA) to mitogen activated protein kinase (MAPK) pathways in the spleen. Beta₂-AR signal "shutdown" in the spleen and switching from PKA to G-coupled protein receptor kinase (GRK) pathways in lymph node cells drives inflammation and disease advancement. Based on these findings and the existing literature in other IMIDs, we present and discuss relevant literature that support the hypothesis that unresolvable immune stimulation from chronic inflammation leads to a maladaptive disease-inducing and perpetuating sympathetic response in an attempt to maintain allostasis. Since the role of sympathetic dysfunction in IMIDs is best studied in RA and rodent models of RA, this IMID is the primary one used to evaluate data relevant to our hypothesis. Here, we review the relevant literature and discuss sympathetic dysfunction as a significant contributor to the pathophysiology of IMIDs, and then discuss a novel target for treatment. Based on our findings in inflammatory arthritis and our understanding of common inflammatory process that are used by the immune system across all IMIDs, novel strategies to restore SNS homeostasis are expected to provide safe, cost-effective approaches to treat IMIDs, lower comorbidities, and increase longevity.

Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings.

PubMed

Baysal-Kirac, Leyla; Tuzun, Erdem; Erdag, Ece; Ulusoy, Canan; Vanli-Yavuz, Ebru Nur; Ekizoglu, Esme; Peach, Sian; Sezgin, Mine; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen; Vincent, Angela; Baykan, Betul

2016-03-01

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Cardiac autonomic function and hot flashes among perimenopausal and postmenopausal women.

PubMed

Gibson, Carolyn J; Mendes, Wendy Berry; Schembri, Michael; Grady, Deborah; Huang, Alison J

2017-07-01

Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic activity and hot flashes in perimenopausal and postmenopausal women. Autonomic function was assessed at baseline and 12 weeks among perimenopausal and postmenopausal women (n = 121, mean age 53 years) in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, was measured with impedance cardiography. Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, was measured with electrocardiography. Participants self-reported hot flash frequency and severity in 7-day symptom diaries. Analysis of covariance models were used to relate autonomic function and hot flash frequency and severity at baseline, and to relate changes in autonomic function to changes in hot flash frequency and severity over 12 weeks, adjusting for age, body mass index, and intervention assignment. PEP was not associated with hot flash frequency or severity at baseline or over 12 weeks (P > 0.05 for all). In contrast, there was a trend toward greater frequency of moderate-to-severe hot flashes with higher RSA at baseline (β = 0.43, P = 0.06), and a positive association between change in RSA and change in frequency of moderate-to-severe hot flashes over 12 weeks (β = 0.63, P = 0.04). Among perimenopausal and postmenopausal women with hot flashes, variations in hot flash frequency and severity were not explained by variations in resting sympathetic activation. Greater parasympathetic activation was associated with more frequent moderate-to-severe hot flashes, which may reflect increased sensitivity to perceiving hot flashes.

Genital herpes simplex virus infections: clinical manifestations, course, and complications.

PubMed

Corey, L; Adams, H G; Brown, Z A; Holmes, K K

1983-06-01

The clinical course and complications of 268 patients with first episodes and 362 with recurrent episodes of genital herpes infection were reviewed. Symptoms of genital herpes were more severe in women than in men. Primary first-episode genital herpes was accompanied by systemic symptoms (67%), local pain and itching (98%), dysuria (63%), and tender adenopathy (80%). Patients presented with several bilaterally distributed postular ulcerative lesions that lasted a mean of 19.0 days. Herpes simplex virus was isolated from the urethra, cervix, and pharynx of 82%, 88%, and 13% of women with first-episode primary genital herpes, and the urethra and pharynx of 28% and 7% of men. Complications included aseptic meningitis (8%), sacral autonomic nervous system dysfunction (2%), development of extragenital lesions (20%), and secondary yeast infections (11%). Recurrent episodes were characterized by small vesicular or ulcerative unilaterally distributed lesions that lasted a mean of 10.1 days. Systemic symptoms were uncommon and 25% of recurrent episodes were asymptomatic. The major concerns of patients were the frequency of recurrences and fear of transmitting infection to partners or infants.

Ecstatic Epileptic Seizures: A Glimpse into the Multiple Roles of the Insula.

PubMed

Gschwind, Markus; Picard, Fabienne

2016-01-01

Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and "enhanced self-awareness." They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n = 52); a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective, and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura.

Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea

PubMed Central

Macey, Paul M.; Kumar, Rajesh; Woo, Mary A.; Yan-Go, Frisca L.; Harper, Ronald M.

2013-01-01

Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean±std: 52.1±8.1 years; 31 male aged 54.3±8.4 years), and 57 healthy control subjects (20 female, 50.5±8.1 years; 37 male, 45.6±9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: −0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies. PMID:24194842

Heart rate variability in stroke patients submitted to an acute bout of aerobic exercise.

PubMed

Raimundo, Rodrigo Daminello; de Abreu, Luiz Carlos; Adami, Fernando; Vanderlei, Franciele Marques; de Carvalho, Tatiana Dias; Moreno, Isadora Lessa; Pereira, Valdelias Xavier; Valenti, Vitor Engracia; Sato, Monica Akemi

2013-10-01

Stroke has been associated with cardiac autonomic impairment due to damage in central nervous system. Dysfunction in heart rate variability (HRV) may reflect dysfunction of the autonomic nervous system. Aerobic training has been used in the rehabilitation procedure of patients, due to improvement of aerobic function and other beneficial effects as increased recruitment of motor units, favoring the development of muscle fibers. The purpose of this study was to evaluate the cardiac autonomic modulation in patients with stroke before, during, and after an acute bout of aerobic exercise. The heart rate of 38 stroke patients was recorded using a heart rate (HR) monitor and the data were used to assess cardiac autonomic modulation through HRV analysis. The patients were in supine position and remained at resting condition (R) for 10 min before starting the experiment. Afterwards, they were submitted to walking exercise (E) on a treadmill until achieve 50-70% of maximum heart rate. After 30 min of aerobic exercise, the subjects were advised to remain in supine position for additional 30 min in order to record the HR during the recovery (RC) period. The recordings were divided in three periods: RC1, immediately after the end of exercise bout, RC2, between 12 and 17 min of recovery, and RC3, at the final 5 min of recovery. A significant decrease was observed during exercise in the MeanRR index (577.3±92 vs. 861.1+109), RRtri (5.1±2 vs. 9.1±3), high frequency component (11.2±4 vs. 167±135 ms) and SD1 (5.7±2 vs. 16.9±7 ms) compared to resting values. The SDNN index reduced during E (27.6±19) and RC1 (29.9±11), RC2 (27.9±9) and RC3 (32.4±13) compared to resting values (42.4±19). The low frequency component increased during E (545±82), but decreased during RC1 (166.3±129), RC2 (206.9±152), and RC3 (249.5±236) compared to R levels (394.6±315). These findings suggest that stroke patients showed a reduced HRV during and at least 30 min after exercise, due to an autonomic imbalance reflected by increased indexes that represent the sympathetic nervous system.

Analysis of autonomous vehicle policies.

DOT National Transportation Integrated Search

2017-01-01

The rapid development and adoption of connected and autonomous vehicles will transform the U.S. transportation system over the next 30 years. Although the widespread use of fully connected and autonomous vehicles is still several years away, it is no...

[Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

PubMed

Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

2014-08-01

Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

Cardioprotective Properties of Aerobic and Resistance Training Against Myocardial Infarction.

PubMed

Barboza, C A; Souza, G I H; Oliveira, J C M F; Silva, L M; Mostarda, C T; Dourado, P M M; Oyama, L M; Lira, F S; Irigoyen, M C; Rodrigues, B

2016-06-01

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+myocardial infarction, aerobic trained+myocardial infarction, and resistance trained+myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. © Georg Thieme Verlag KG Stuttgart · New York.

Integrity of central nervous function in diabetes mellitus assessed by resting state EEG frequency analysis and source localization.

PubMed

Frøkjær, Jens B; Graversen, Carina; Brock, Christina; Khodayari-Rostamabad, Ahmad; Olesen, Søren S; Hansen, Tine M; Søfteland, Eirik; Simrén, Magnus; Drewes, Asbjørn M

2017-02-01

Diabetes mellitus (DM) is associated with structural and functional changes of the central nervous system. We used electroencephalography (EEG) to assess resting state cortical activity and explored associations to relevant clinical features. Multichannel resting state EEG was recorded in 27 healthy controls and 24 patients with longstanding DM and signs of autonomic dysfunction. The power distribution based on wavelet analysis was summarized into frequency bands with corresponding topographic mapping. Source localization analysis was applied to explore the electrical cortical sources underlying the EEG. Compared to controls, DM patients had an overall decreased EEG power in the delta (1-4Hz) and gamma (30-45Hz) bands. Topographic analysis revealed that these changes were confined to the frontal region for the delta band and to central cortical areas for the gamma band. Source localization analysis identified sources with reduced activity in the left postcentral gyrus for the gamma band and in right superior parietal lobule for the alpha1 (8-10Hz) band. DM patients with clinical signs of autonomic dysfunction and gastrointestinal symptoms had evidence of altered resting state cortical processing. This may reflect metabolic, vascular or neuronal changes associated with diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

4A syndrome: ocular surface investigation in an Italian young patient.

PubMed

Aragona, Pasquale; Rania, Laura; Roszkowska, Anna Maria; Puzzolo, Domenico; Micali, Antonio; Pisani, Antonina; Salzano, Giuseppina; Messina, Maria Francesca

2014-12-08

Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

Clinical study on the treatment of vertigo by ant vertigo

NASA Astrophysics Data System (ADS)

Liu, Xiaobin; Li, Chongxian; Hao, Shaojun; Lian, Linlin; Chen, Weiliang; Wang, Hongyu; Guan, Zhijiang; Zhang, Zhengchen

2018-04-01

To observe the clinical curative effect of antiglare granule in the treatment of hypertension, cerebral arteriosclerosis, vertebrobasilar artery insufficiency, Meniere's disease, autonomic dysfunction caused by vertigo etc, the patients with vertigo were randomly divided into 300 cases of cerebral arteriosclerosis, vertebral basilar artery insufficiency, Meniere's disease into three groups, treatment group: control group 1, 2 groups of. 3 times a day, 30 days for a course of treatment, once a two treatment, observation and treatment effect. Control group: conventional doses of Yangxue Qingnao Granule, enteric coated aspirin treatment ibid. After 2 courses of treatment were observed and recorded the key concept of vertigo degree change number. Compare the outcome of TCM symptom medication after February, the total effective rate of treatment group was 96%, 1 in the control group the total efficiency of 69.7%, 2 in the control group the total efficiency of 71.7%, the treatment group curative effect on the treatment of hypertension, cerebral arteriosclerosis, vertebral basilar artery insufficiency vertigo, Meniere's disease, head weight light, walking foot stable curative effect is better than that of Yangxue Qingnao Granule, enteric coated aspirin effect. Aanti glare granule in the treatment of hypertension, cerebral arteriosclerosis and vertebral basilar artery insufficiency, Meniere's disease, autonomic dysfunction caused by vertigo has good clinical curative effect.

[The prognostic significance of brain-derived neurotrophic factor (BDNF) for phobic anxiety disorders, vegetative and cognitive impairments during conservative treatment including adaptol of some functional and organic diseases of nervous system].

PubMed

Zhivolupov, S A; Samartsev, I N; Marchenko, A A; Puliatkina, O V

2012-01-01

We have studied the efficacy of adaptol in the treatment of 45 patients with somatoform dysfunction of the autonomic nervous system and 30 patients with closed head injury. The condition of patients during the treatment was evaluated with clinical and neuropsychological scales. The serum level of BDNF before and after the treatment has been studied as well. Adaptol has been shown to enhance the production of BDNF, reduce significantly the intensity of anxiety, autonomic disorders and improve intellectual processes. The dose-dependent effect of the drug has been demonstrated. In conclusion, adaptol can be recommended for treatment of diseases that demand stimulation of neuroplasticity in the CNS.

Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke.

PubMed

Xu, Yan-Hong; Wang, Xing-De; Yang, Jia-Jun; Zhou, Li; Pan, Yong-Chao

2016-01-01

Autonomic dysfunction is common after stroke, which is correlated with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we used this technique for the first time to investigate the cardiac autonomic function of patients with acute hemispheric ischemic stroke. A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC, heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD and also studied the correlations between these parameters and NIHSS scores. The R-R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=-0.279, r=-0.266, and r=-0.319; P=0.027, P=0.035, and P=0.011). Both DC and AC of heart rate decreased in patients with hemispheric infarction, reflecting a decrease in both vagal and sympathetic modulation. Both DC and AC were correlated with the severity of stroke.

Photobiomodulation on alcohol induced dysfunction

NASA Astrophysics Data System (ADS)

Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

2007-05-01

Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

Attachment representations among substance-abusing women in transition to motherhood: implications for prenatal emotions and mother-infant interaction.

PubMed

Isosävi, Sanna; Flykt, Marjo; Belt, Ritva; Posa, Tiina; Kuittinen, Saija; Puura, Kaija; Punamäki, Raija-Leena

2016-08-01

We studied how attachment representations contribute to central components of transition to motherhood, prenatal emotion processing (EP) and emotional availability (EA) of mother-infant interaction, and whether there are group specific differences. Participants were 51 treatment-enrolled substance-abusing (SA) mothers and their infants and 50 non-using comparison dyads with obstetric risk. Mother's attachment representations (AAI) and EP were assessed prenatally and EA when infants were four months. Results showed that autonomous attachment only had a buffering effect on prenatal EP among comparisons. All SA mothers showed more dysfunctional EP than comparisons and, contrary to comparisons, autonomous SA mothers reported more negative cognitive appraisals and less meta-evaluation of emotions than dismissing SA mothers. Preoccupied SA mothers showed high negative cognitive appraisals, suggesting under-regulation of emotions. Attachment representations were not associated with EA in either group; rather, SA status contributed to global risk in the relationship. Surprisingly, autonomous SA mothers showed a tendency towards intrusiveness. We propose that obstetric risk among comparisons and adverse relational experiences among almost all SA mothers might override the protective role of mother's autonomous representations for dyadic interaction. We conclude that prenatal emotional turbulence and high interaction risk of all SA mothers calls for holistic treatment for the dyad.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

PubMed

Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2011-04-01

To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials.

PubMed

Suanprasert, N; Berk, J L; Benson, M D; Dyck, P J B; Klein, C J; Gollob, J A; Bettencourt, B R; Karsten, V; Dyck, P J

2014-09-15

Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests. Copyright © 2014 Elsevier B.V. All rights reserved.

MeCP2 Deficiency Leads to Loss of Glial Kir4.1

PubMed Central

Cuddapah, Vishnu A.; Pacheco, Natasha L.; Holt, Leanne M.; Percy, Alan K.

2018-01-01

Abstract Rett syndrome (RTT) is an X-linked neurodevelopmental disorder usually caused by mutations in methyl-CpG-binding protein 2 (MeCP2). RTT is typified by apparently normal development until 6–18 mo of age, when motor and communicative skills regress and hand stereotypies, autonomic symptoms, and seizures present. Restoration of MeCP2 function selectively to astrocytes reversed several deficits in a murine model of RTT, but the mechanism of this rescue is unknown. Astrocytes carry out many essential functions required for normal brain functioning, including extracellular K+ buffering. Kir4.1, an inwardly rectifying K+ channel, is largely responsible for the channel-mediated K+ regulation by astrocytes. Loss-of-function mutations in Kir4.1 in human patients result in a severe neurodevelopmental disorder termed EAST or SESAME syndrome. Here, we evaluated astrocytic Kir4.1 expression in a murine model of Rett syndrome. We demonstrate by chromatin immunoprecipitation analysis that Kir4.1 is a direct molecular target of MeCP2. Astrocytes from Mecp2-deficient mice express significantly less Kir4.1 mRNA and protein, which translates into a >50% deficiency in Ba2+-sensitive Kir4.1-mediated currents, and impaired extracellular potassium dynamics. By examining astrocytes in isolation, we demonstrate that loss of Kir4.1 is cell autonomous. Assessment through postnatal development revealed that Kir4.1 expression in Mecp2-deficient animals never reaches adult, wild-type levels, consistent with a neurodevelopmental disorder. These are the first data implicating a direct MeCP2 molecular target in astrocytes and provide novel mechanistic insight explaining a potential mechanism by which astrocytic dysfunction may contribute to RTT. PMID:29464197

Phrenic Nerve Conduction Study in the Early Stage of Guillain-Barre Syndrome as a Predictor of Respiratory Failure.

PubMed

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

PubMed Central

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure. PMID:29720799

Using the autonomic standards to assess orthostatic hypotension in persons with SCI: a case series.

PubMed

Wecht, Jill M; Wilson, James; Previnaire, Jean-Gabriel

2017-01-01

Spinal cord injury (SCI) creates a complex and unique syndrome of medical issues related to disruption of somatic and autonomic pathways. Among these impaired control of blood pressure (BP) can significantly impede patients' activities of daily living. The International Standards for the Assessment of Autonomic Function after SCI (ISAFSCI) is used to document the impact of SCI on resting BP (abnormal if below 90 mmHg) and the presence or absence of orthostatic hypotension (OH), defined as a symptomatic or asymptomatic decrease in BP (>/=20/10 mmHg) upon moving to an upright position. Case 1 documents the adverse influence of prescribed medications (antidepressants for neuropathic pain) on OH; case 2 describes the influence of bladder management on cardiovascular instability (autonomic dysreflexia and subsequent OH); case 3 describes the association between spasticity and OH; case 4 describes OH associated with a Valsalva maneuver. Impaired control of BP can stem from a combination of medical issues and autonomic dysfunction in persons with SCI. Management strategies for OH will vary depending on the stage of the SCI, the root cause of the OH and other confounding medical conditions. Non-pharmacological treatment should be considered as a first line of intervention and consideration should be given to cessation of potentially contributory medications prior to implementing pharmaceutical interventions. The systematic use of ISAFSCI by clinicians is recommended to document BP irregularities and to describe the effects of treatment strategies aimed at improving BP control in the SCI population.

Autonomic stress reactivity and craving in individuals with problematic Internet use.

PubMed

Moretta, Tania; Buodo, Giulia

2018-01-01

The link between autonomic stress reactivity and subjective urge/craving has been less systematically examined in behavioral addictions (i.e. problematic Internet use) than in substance use disorders. The present study investigated whether problematic Internet users (PU) show enhanced autonomic stress reactivity than non-PU, indexed by lower Heart Rate Variability (HRV) and higher Skin Conductance Level (SCL) reactivity during the Trier Social Stress Test (TSST), whether greater reactivity is related to stronger Internet craving, and whether problematic Internet usage is associated with some dysfunctional psychological features. Based on their Internet Addiction Test scores, participants were divided into PU (N = 24) and non-PU (N = 21). Their heart rate and skin conductance were continuously recorded during baseline, social stressors, and recovery. Craving for Internet usage were collected using a Likert scale before and after the TSST. The SDNN, an overall measure of HRV, was significantly lower in PU than non-PU during baseline, but not during and after stressful task. Furthermore, only among PU a significant negative correlation emerged between SDNN during recovery and craving ratings after the test. No group differences emerged for SCL. Lastly, PU endorsed more mood, obsessive-compulsive, and alcohol-related problems. Our findings suggest that problems in controlling one's use of the Internet may be related to reduced autonomic balance at rest. Moreover, our results provide new insights into the characterization of craving in PIU, indicating the existence of a relationship between craving for Internet usage and reduced autonomic flexibility.

Psychophysiological Associations with Gastrointestinal Symptomatology in Autism Spectrum Disorder

PubMed Central

Ferguson, Bradley J.; Marler, Sarah; Altstein, Lily L.; Lee, Evon Batey; Akers, Jill; Sohl, Kristin; McLaughlin, Aaron; Hartnett, Kaitlyn; Kille, Briana; Mazurek, Micah; Macklin, Eric A.; McDonnell, Erin; Barstow, Mariah; Bauman, Margaret L.; Margolis, Kara Gross; Veenstra-VanderWeele, Jeremy; Beversdorf, David Q.

2017-01-01

Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan. PMID:27321113

Thermodysregulation in persons with spinal cord injury: case series on use of the autonomic standards.

PubMed

Handrakis, John P; Trbovich, Michelle; Hagen, Ellen Merete; Price, Michael

2017-01-01

The ability to maintain core body temperature (Tcore) within a narrow range (37 ± 0.6 °C), despite exposure to a wide range of ambient temperatures, is essential in order to provide an optimal environment for vital organs, the central nervous system (CNS), and cellular processes to function. High-level (above T6) spinal cord injury (SCI) interrupts the autonomic nervous system's ability to carry out hypothalamic regulation of thermoregulatory mechanisms for both heat dissipation and conservation. This interruption leaves persons with high-level SCI vulnerable to hyper and hypothermia even during exposure to relatively mild ambient temperatures. The goal of the Autonomic Standards is to enable the clinician to quickly identify those individuals with SCI who may be most at risk for thermoregulatory dysfunction. Case 1: Heat Exhaustion, Case 2: Heat Stroke in absence of CNS symptoms, Case 3: Heat Exhaustion. The three cases demonstrate the signs and symptoms that may accompany hyperthermia in persons with SCI. The onset may be quite rapid and the condition persistent, despite ambient temperatures being much less intense than expected to be necessary to induce similar conditions in able-bodied (AB) persons. The responses of the persons in the case studies to the temperature regulation and autonomic control of sweating sections of the Autonomic Standards would identify them as being vulnerable and warrant providing appropriate exposure guidelines and precautions to them and their caregivers.

Abnormal heart rate recovery and deficient chronotropic response after submaximal exercise in young Marfan syndrome patients.

PubMed

Peres, Paulo; Carvalho, Antônio C; Perez, Ana Beatriz A; Medeiros, Wladimir M

2016-10-01

Marfan syndrome patients present important cardiac structural changes, ventricular dysfunction, and electrocardiographic changes. An abnormal heart rate response during or after exercise is an independent predictor of mortality and autonomic dysfunction. The aim of the present study was to compare heart rate recovery and chronotropic response obtained by cardiac reserve in patients with Marfan syndrome subjected to submaximal exercise. A total of 12 patients on β-blocker therapy and 13 off β-blocker therapy were compared with 12 healthy controls. They were subjected to submaximal exercise with lactate measurements. The heart rate recovery was obtained in the first minute of recovery and corrected for cardiac reserve and peak lactate concentration. Peak heart rate (141±16 versus 155±17 versus 174±8 bpm; p=0.001), heart rate reserve (58.7±9.4 versus 67.6±14.3 versus 82.6±4.8 bpm; p=0.001), heart rate recovery (22±6 versus 22±8 versus 34±9 bpm; p=0.001), and heart rate recovery/lactate (3±1 versus 3±1 versus 5±1 bpm/mmol/L; p=0.003) were different between Marfan groups and controls, respectively. All the patients with Marfan syndrome had heart rate recovery values below the mean observed in the control group. The absolute values of heart rate recovery were strongly correlated with the heart rate reserve (r=0.76; p=0.001). Marfan syndrome patients have reduced heart rate recovery and chronotropic deficit after submaximal exercise, and the chronotropic deficit is a strong determinant of heart rate recovery. These changes are suggestive of autonomic dysfunction.

Predictors of response to a behavioral treatment in patients with chronic gastric motility disorders

NASA Technical Reports Server (NTRS)

Rashed, Hani; Cutts, Teresa; Abell, Thomas; Cowings, Patricia; Toscano, William; El-Gammal, Ahmed; Adl, Dima

2002-01-01

Chronic gastric motility disorders have proven intractable to most traditional therapies. Twenty-six patients with chronic nausea and vomiting were treated with a behavioral technique, autonomic training (AT) with directed imagery (verbal instructions), to help facilitate physiological control. After treatment, gastrointestinal symptoms decreased by >30% in 58% of the treated patients. We compared those improved patients to the 43% who did not improve significantly. No significant differences existed in baseline symptoms and autonomic measures between both groups. However, baseline measures of gastric emptying and autonomic function predicted treatment outcome. Patients who improved manifested mild to moderate delay in baseline gastric emptying measures. The percent of liquid gastric emptying at 60 mins and the sympathetic adrenergic measure of percent of change in the foot cutaneous blood flow in response to cold stress test predicted improvement in AT outcome, with clinical diagnostic values of 77% and 71%, respectively. We conclude that AT treatment can be efficacious in some patients with impaired gastric emptying and adrenergic dysfunction. More work is warranted to compare biofeedback therapy with gastric motility patients and controls in population-based studies.

Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

PubMed

Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

2018-03-01

Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia normally act to mitigate neurodegeneration in ALS/FTLD? To what extent do cellular signaling pathways mediate non-cell autonomous communications between distinct central nervous system (CNS) cell types during disease? Is it possible to therapeutically target specific cell types in the CNS?

Laparoscopic anatomy of the autonomic nerves of the pelvis and the concept of nerve-sparing surgery by direct visualization of autonomic nerve bundles.

PubMed

Lemos, Nucelio; Souza, Caroline; Marques, Renato Moretti; Kamergorodsky, Gil; Schor, Eduardo; Girão, Manoel J B C

2015-11-01

To demonstrate the laparoscopic neuroanatomy of the autonomic nerves of the pelvis using the laparoscopic neuronavigation technique, as well as the technique for a nerve-sparing radical endometriosis surgery. Step-by-step explanation of the technique using videos and pictures (educational video) to demonstrate the anatomy of the intrapelvic bundles of the autonomic nerve system innervating the bladder, rectum, and pelvic floor. Tertiary referral center. One 37-year-old woman with an infiltrative endometriotic nodule on the anterior third of the left uterosacral ligament and one 34-year-old woman with rectovaginal endometriosis. Exposure and preservation by direct visualization of the hypogastric nerve and the inferior hypogastric plexus. Visual control and identification of the autonomic nerve branches of the posterior pelvis. Exposure and preservation of the hypogastric nerve and the superficial part of the left hypogastric nerve were achieved on the first patient. Nerve roots S2, S3, and S4 were identified on the second patient, allowing for the exposure and preservation of the pelvic splanchnic nerves and the deep portion inferior hypogastric plexus. Radical surgery for endometriosis can induce urinary dysfunction in 2.4%-17.5% of patients owing to lesion of the autonomic nerves. The surgeon's knowledge of the anatomy of these nerves is the main factor for preserving postoperative urinary function. The following nerves are the intrapelvic part of the autonomic nervous system: the hypogastric nerves, which derive from the superior hypogastric plexus and carry the sympathetic signals to the internal urethral and anal sphincters as well as to the pelvic visceral proprioception; and the pelvic splanchnic nerves, which arise from S2 to S4 and carry nociceptive and parasympathetic signals to the bladder, rectum, and the sigmoid and left colons. The hypogastric and pelvic splanchnic nerves merge into the pararectal fossae to form the inferior hypogastric plexus. Most of the nerve-sparing techniques involve the dissection and exposure of the pelvic splanchnic nerves and the inferior hypogastric plexus. However, knowledge of the topographic anatomy and awareness of the landmarks for avoiding intraoperative nerve injuries seem to be the most important factors in avoiding postoperative bladder and bowel dysfunction, although this latter nerve-sparing technique seems to be associated with reduced radicality and symptom persistence. This video demonstrates a technique to expose the sympathetic and parasympathetic nerves of the pelvis to preserve them in radical pelvic surgery, by means of direct visualization, in a similar fashion to the technique used to preserve the ureters. An alternative to this technique is to use landmarks for limiting dissection and avoiding intraoperative nerve injury. Despite being safe and more easily reproducible, this latter technique is associated with a higher rate of symptom persistence. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat.

PubMed

Johnson, Megan S; DeMarco, Vincent G; Heesch, Cheryl M; Whaley-Connell, Adam T; Schneider, Rebecca I; Rehmer, Nathan T; Tilmon, Roger D; Ferrario, Carlos M; Sowers, James R

2011-10-01

The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensin-aldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension.

The impact of major depression on heart rate variability and endothelial dysfunction in patients with stable coronary artery disease.

PubMed

Aydin Sunbul, Esra; Sunbul, Murat; Gulec, Huseyin

Depression is an independent risk factor in cardiovascular diseases. Changes in the cardiac autonomic functions and pro-inflammatory processes are potential biological factors. Endothelial dysfunction plays an important role in the etiopathogenesis of atherosclerosis. Our objective was to evaluate the impact of major depression on heart rate variability and endothelial dysfunction in patients with stable CAD. The study group included 65 CAD patients with a diagnosis of major depression and 54 CAD patients without major depression. All study population underwent transthoracic echocardiography, measurement of flow mediated dilatation (FMD) and 24-h holter recording for heart rate variability (HRV). Blood samples were drawn to determine the inflammatory parameters. Severity of depressive episode was assessed by Montgomery-Asberg Depression Scale (MADRS). The distribution of age and sex was similar in the patient and control groups (P=0.715, 0.354, respectively). There was no significant difference in medications used between the groups. Echocardiographic parameters were similar between the groups. Inflammatory parameters were also similar between the groups. HRV parameters were significantly lower in the patient group than controls. The absolute FMD value and percentage FMD were significantly lower in the patient group than controls (P<0.001). The MADRS score correlated with pNN50 in both groups (P<0.05), and with FMD in the control group (P<0.001), even after adjusting for age and gender (P<0.001). MADRS score was an independent predictor of pNN50 level, percentage and absolute FMD values regardless of age and gender. Clinician should pay more attention for evaluation of depressive patients with CAD. Copyright © 2016 Elsevier Inc. All rights reserved.

System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy

NASA Technical Reports Server (NTRS)

Mukkamala, R.; Mathias, J. M.; Mullen, T. J.; Cohen, R. J.; Freeman, R.

1999-01-01

We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.

Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review.

PubMed

Kulshreshtha, Poorvi; Deepak, Kishore K

2013-03-01

This review imparts an impressionistic tone to our current understanding of autonomic nervous system abnormalities in fibromyalgia. In the wake of symptoms present in patients with fibromyalgia (FM), autonomic dysfunction seems plausible in fibromyalgia. A popular notion is that of a relentless sympathetic hyperactivity and hyporeactivity based on heart rate variability (HRV) analyses and responses to various physiological stimuli. However, some exactly opposite findings suggesting normal/hypersympathetic reactivity in patients with fibromyalgia do exist. This heterogeneous picture along with multiple comorbidities accounts for the quantitative and qualitative differences in the degree of dysautonomia present in patients with FM. We contend that HRV changes in fibromyalgia may not actually represent increased cardiac sympathetic tone. Normal muscle sympathetic nerve activity (MSNA) and normal autonomic reactivity tests in patients with fibromyalgia suggest defective vascular end organ in fibromyalgia. Previously, we proposed a model linking deconditioning with physical inactivity resulting from widespread pain in patients with fibromyalgia. Deconditioning also modulates the autonomic nervous system (high sympathetic tone and a low parasympathetic tone). A high peripheral sympathetic tone causes regional ischaemia, which in turn results in widespread pain. Thus, vascular dysregulation and hypoperfusion in patients with FM give rise to ischaemic pain leading to physical inactivity. Microvascular abnormalities are also found in patients with FM. Therapeutic interventions (e.g. exercise) that result in vasodilatation and favourable autonomic alterations have proven to be effective. In this review, we focus on the vascular end organ in patients with fibromyalgia in particular and its modulation by exercise in general. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Causes of chronic orthostatic hypotension

NASA Technical Reports Server (NTRS)

Robertson, D.; Robertson, R. M.

1994-01-01

OBJECTIVE: To determine the frequency of various causes of orthostatic hypotension. DESIGN: Survey. SETTING: Tertiary referral center. PATIENTS: One hundred patients with moderate to severe orthostatic hypotension. RESULTS: Twenty-seven percent of the patients had primary autonomic failure, 35% had secondary autonomic failure, and 38% had hypotension without evidence of generalized autonomic degeneration. CONCLUSIONS: In a tertiary referral center, only a minority of patients with severe orthostatic hypotension will have Shy-Drager syndrome or Bradbury-Eggleston syndrome as their primary disease. Occasional patients who initially appear to have Bradbury-Eggleston syndrome ultimately prove to have Shy-Drager syndrome or paraneoplastic autonomic failure. Antidepressant drugs, even in low doses, remain a major overlooked cause of orthostatic hypotension.

The choreography of neuroinflammation in Huntington’s disease

PubMed Central

Crotti, Andrea; Glass, Christopher K.

2016-01-01

Currently, the concept of ‘neuroinflammation’ includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. The roles of brain-resident and peripheral immune cells in these inflammatory settings are poorly understood, and it is unclear whether neuroinflammation results from immune reaction to neuronal dysfunction/degeneration, and/or represents cell-autonomous phenotypes of dysfunctional immune cells. Here, we review recent studies examining these questions in the context of Huntington’s disease (HD), where mutant Huntingtin (HTT) is expressed in both neurons and glia. Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenerative disease pathogenesis. PMID:26001312

Neuropeptides in Lower Urinary Tract (LUT) Function

PubMed Central

Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Numerous neuropeptide/receptor systems including vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, substance P, neurokinin A, bradykinin, and endothelin-1 are expressed in the lower urinary tract (LUT) in both neural and non-neural (e.g., urothelium) components. LUT neuropeptide immunoreactivity is present in afferent and autonomic efferent neurons innervating the bladder and urethra and in the urothelium of the urinary bladder. Neuropeptides have tissue-specific distributions and functions in the LUT and exhibit neuroplastic changes in expression and function with LUT dysfunction following neural injury, inflammation and disease. LUT dysfunction with abnormal voiding including urinary urgency, increased voiding frequency, nocturia, urinary incontinence and pain may reflect a change in the balance of neuropeptides in bladder reflex pathways. LUT neuropeptide/receptor systems may represent potential targets for therapeutic intervention. PMID:21290237

[Trigemino-autonomic headache syndromes].

PubMed

Busch, V; May, A

2003-01-01

This review describes the characteristics of some rare severe primary headache syndromes without any structural lesions, which are summarized as the trigemino-autonomic headaches. Pain in these syndromes is associated with autonomic symptoms such as conjunctival injection, lacrimation, rhinorrhoe, ptosis or eyelid edema. This article summarizes the diagnostics, epidemiology and therapy of these conditions.

Heart rate variability and heart rate turbulence in patients with polycystic ovary syndrome.

PubMed

Özkeçeci, Gülay; Ünlü, Bekir Serdar; Dursun, Hüseyin; Akçi, Önder; Köken, Gülengül; Onrat, Ersel; Avşar, Alaettin

2016-05-01

Cardiac autonomic dysfunction may develop in patients with polycystic ovary syndrome (PCOS). Heart rate variability (HRV) and heart rate turbulence (HRT) are used in assessing cardiac autonomic functions. The goal of this study was to compare the cardiac autonomic functions in patients with PCOS and healthy controls. To our knowledge, this is the first study evaluating cardiac autonomic functions in patients with PCOS with respect to both HRV and HRT. Twenty-three patients with PCOS (mean age 22.8±3.9 years) and 25 healthy female volunteers who were matched for age and body mass index (BMI) (mean age 23.5±6.2 years) were enrolled in this as case-control study. Twenty-four hour ambulatory electrocardiogram recordings of all participants were taken using Pathfinder software. The time domain parameters of HRV and HRT, including turbulence onset (TO) and turbulence slope, were calculated. Diagnosis of PCOS was made with physical and laboratory findings of hirsutism or biochemical hyperandrogenism and chronic anovulation. Diabetes mellitus, other hormon disorders or hormon therapy, pregnancy, atrial fibrilation, obesite, chronic diseases, disorders of the autonomic nervous system, a history of drug use affecting the autonomic nervous system were excluded. There were no significant differences in HRV and HRT parameters between the two groups. Cardiovascular risk factors, such as BMI, blood pressure, fasting blood glucose, and lipid parameters, were also similar. Triangular index measure of HRV was negatively correlated with high density lipoprotein cholesterol levels (r=-0.47, p<0.05), while age and BMI were significantly correlated with TO (r=0.31 and 0.47, respectively; p<0.05 for all). Cardiac autonomic functions were not found to be altered in patients with PCOS in comparison with healthy controls. These results may be explained with the absence of concomitant cardiovascular risk factors with the patients being in the early stage of the disease.

Strengthening exercises improve symptoms and quality of life but do not change autonomic modulation in fibromyalgia: a randomized clinical trial.

PubMed

Gavi, Maria Bernadete Renoldi Oliveira; Vassalo, Dalton Valentin; Amaral, Fabian Tadeu; Macedo, Danielle Constância Felício; Gava, Pablo Lúcio; Dantas, Eduardo Miranda; Valim, Valéria

2014-01-01

Autonomic dysfunction is an important mechanism that could explain many symptoms observed in fibromyalgia (FM). Exercise is an effective treatment, with benefits potentially mediated through changes in autonomic modulation. Strengthening is one of the less studied exercises in FM, and the acute and chronic effects of strengthening on the autonomic system remain unknown. The objective of this study was to assess the chronic effects of strengthening exercises (STRE) on autonomic modulation, pain perception and the quality of life (QOL) of FM patients. Eighty sedentary women with FM (ACR 1990) were randomly selected to participate in STRE or flexibility (FLEX) exercises in a blinded controlled trial. The intensity of STRE was set at 45% of the estimated load of 1 Repetition Maximum (RM) in 12 different exercises. Outcomes were Visual Analog Scale (VAS) for pain, Heart Rate Variability (HRV) analysis, treadmill test, the sit and reach test (Wells and Dillon's Bench), maximal repetitions test and handgrip dynamometry; and quality of life by the Fibromyalgia Impact Questionnaire (FIQ), the Beck and Idate Trait-State Inventory (IDATE), a short-form health survey (SF-36). The STRE group was more effective to strength gain for all muscles and pain control after 4 and 16 weeks (p<0.05). The FLEX group showed higher improvements in anxiety (p<0.05). Both groups showed improvements in the QOL, and there was no significant difference observed between the groups. There was no change in the HRV of the STRE and FLEX groups. Strengthening exercises show greater and more rapid improvements in pain and strength than flexibility exercises. Despite the benefits in fitness, pain, depression, anxiety and quality of life, no effect was observed on the autonomic modulation in both groups. This observation suggests that changes in autonomic modulation are not a target tobe clinically achieved in fibromyalgia. ClinicalTrials.gov NCT02004405.

Impaired social response reversal. A case of 'acquired sociopathy'.

PubMed

Blair, R J; Cipolotti, L

2000-06-01

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.

Cardiac autonomic neuropathy in patients with diabetes mellitus

PubMed Central

Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

2014-01-01

Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. PMID:24567799

The unexplored relationship between the urinary tract infections and the autonomic nervous system

PubMed Central

Hibbing, Michael E.; Conover, Matt S.; Hultgren, Scott J.

2015-01-01

Urinary tract infections (UTIs), the majority of which are caused by uropathogenic E. coli (UPEC), are extremely common infections that preferentially effect women. Additional complicating factors, such as catheterization, diabetes, and spinal cord injuries can increase the frequency and severity of UTIs. The rise of antimicrobial resistant uropathogens and the ability of this disease to chronically recur make the development of alternative preventative and therapeutic modalities a priority. The major symptoms of UTIs, urgency, frequency, and dysuria, are readouts of the autonomic nervous system (ANS) and the majority of the factors that lead to complicated UTIs have been shown to impact ANS function. This review summarizes the decades long efforts to understand the molecular mechanisms of the interactions between UPEC and the host, with a particular focus on the recent findings revealing the molecular, bacteriological, immunological and epidemiological complexity of pathogenesis. Additionally, we describe the progress that has been made in: i) generating vaccines and anti-virulence compounds that prevent and/or treat UTI by blocking bacterial adherence to urinary tract tissue and; ii) elucidating the mechanism by which anti-inflammatories are able to alleviate symptoms and improve disease prognosis. Finally, the potential relationships between the ANS and UTI are considered throughout. While these relationships have not been experimentally explored, the known interactions between numerous UTI characteristics (symptoms, complicating factors, and inflammation) and ANS function suggest that UTIs are directly impacting ANS stimulation and that ANS (dys)function may alter UTI prognosis. PMID:26108548

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Neuron-Glia Crosstalk in the Autonomic Nervous System and Its Possible Role in the Progression of Metabolic Syndrome: A New Hypothesis

PubMed Central

Del Rio, Rodrigo; Quintanilla, Rodrigo A.; Orellana, Juan A.; Retamal, Mauricio A.

2015-01-01

Metabolic syndrome (MS) is characterized by the following physiological alterations: increase in abdominal fat, insulin resistance, high concentration of triglycerides, low levels of HDL, high blood pressure, and a generalized inflammatory state. One of the pathophysiological hallmarks of this syndrome is the presence of neurohumoral activation, which involve autonomic imbalance associated to hyperactivation of the sympathetic nervous system. Indeed, enhanced sympathetic drive has been linked to the development of endothelial dysfunction, hypertension, stroke, myocardial infarct, and obstructive sleep apnea. Glial cells, the most abundant cells in the central nervous system, control synaptic transmission, and regulate neuronal function by releasing bioactive molecules called gliotransmitters. Recently, a new family of plasma membrane channels called hemichannels has been described to allow the release of gliotransmitters and modulate neuronal firing rate. Moreover, a growing amount of evidence indicates that uncontrolled hemichannel opening could impair glial cell functions, affecting synaptic transmission and neuronal survival. Given that glial cell functions are disturbed in various metabolic diseases, we hypothesize that progression of MS may relies on hemichannel-dependent impairment of glial-to-neuron communication by a mechanism related to dysfunction of inflammatory response and mitochondrial metabolism of glial cells. In this manuscript, we discuss how glial cells may contribute to the enhanced sympathetic drive observed in MS, and shed light about the possible role of hemichannels in this process. PMID:26648871

Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury

PubMed Central

Cordero, Kathia; Coronel, Gemma G.; Serrano-Illán, Miguel; Cruz-Bracero, Jennifer

2018-01-01

Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with the antioxidant vitamin E (alpha-tocopherol) improves functional recovery after SCI. Female adult Sprague-Dawley rats were fed either with a normal diet or a dietary regiment supplemented with vitamin E (51 IU/g) for eight weeks. The rats were subsequently exposed either to a contusive SCI or sham operation, and evaluated using standard functional behavior analysis. We report that the rats that consumed the vitamin E-enriched diet showed an accelerated bladder recovery and significant improvements in locomotor function relative to controls, as determined by residual volumes and Basso, Beatie, and Bresnaham BBB scores, respectively. Interestingly, the prophylactic dietary intervention did not preserve neurons in the ventral horn of injured rats, but it significantly increased the numbers of oligodendrocytes. Vitamin E supplementation attenuated the depression of the H-reflex (a typical functional consequence of SCI) while increasing the levels of supraspinal serotonin immunoreactivity. Our findings support the potential complementary use of vitamin E to ameliorate sensory and autonomic dysfunctions associated with spinal cord injury, and identified promising new cellular and functional targets of its neuroprotective effects. PMID:29495419

Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

PubMed

Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

2017-01-01

Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

Sexual responsiveness in women with spinal cord injuries: differential effects of anxiety-eliciting stimulation.

PubMed

Sipski, Marca L; Rosen, Raymond C; Alexander, Craig J; Gómez-Marín, Orlando

2004-06-01

Sexual dysfunction is a common problem in women after spinal cord injuries (SCIs). Recently, the use of anxiety-provoking stimulation has been explored as a means of improving sexual responses in able-bodied sexually functional and dysfunctional women. In this laboratory-based study, we assessed the sexual and autonomic responses of women with SCIs with varying degrees of preservation of sympathetic innervation to their genitals to respond to anxiety-provoking audiovisual (AV) stimulation. Subjects were 45 women with SCIs and 11 able-bodied women. For purposes of analysis, SCI subjects were grouped on the basis of the degree of preservation of sensation in the T11-L2 dermatomes. Results revealed that women with low sensory scores in these dermatomes achieved higher vaginal pulse amplitude (VPA) responses to audiovisual erotic stimulation after anxiety preexposure than after neutral preexposure; however, women with SCIs and the greatest degree of preservation of sensory function in the T11-L2 dermatomes, as well as able-bodied controls, did not. Moreover, these same 2 groups of subjects had a decrease in VPA responses during baseline periods in which an anxiety-provoking video sequence was shown, but not during the neutral sequence. It is concluded that these findings are due to the proximity of sensory and autonomic neurologic elements in the spinal cord. Moreover, they demonstrate the differential effects of sympathetic stimulation on genital sexual arousal.

A novel impedance-based cellular assay for the detection of anti-calcium channel autoantibodies in type 1 diabetes.

PubMed

Jackson, Michael W; Gordon, Tom P

2010-09-30

We have recently postulated that functional autoantibodies (Abs) against L-type voltage-gated calcium channels (VGCCs) contribute to autonomic dysfunction in type 1 diabetes (T1D). Previous studies based on whole-organ assays have proven valuable in establishing the mechanism of anti-VGCC Ab activity, but are complex and unsuitable for screening large patient cohorts. In the current study, we used real-time dynamic monitoring of cell impedance to demonstrate that anti-VGCC Abs from patients with T1D inhibit the adherence of Rin A12 cells. The functional effect of the anti-VGCC Abs was mimicked by the dihydropyridine agonist, Bay K8644, and reversed by the antagonist, nicardipine, providing a pharmacological link to the whole-organ studies. IVIg neutralized the effect on cell adhesion of the anti-VGCC Abs, consistent with the presence of anti-idiotypic Abs in IVIg that may prevent the emergence of pathogenic Abs in healthy individuals. The cell impedance assay can be performed in a 96 well plate format, and represents a simple method for detecting the presence of anti-VGCC activity in patient immunoglobulin (IgG). The new cell assay should prove useful for further studies to determine the prevalence of the Ab and its association with symptoms of autonomic dysfunction in patients with T1D. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Sleep-related changes in cardiovascular autonomic regulation in left coronary artery ligation rats: Neural mechanism facilitating arrhythmia after myocardial infarction.

PubMed

Lin, Wei-Lun; Lo, Li-Wei; Chen, Hau-Ruey; Lai, Chun-Ting; Yamada, Shinya; Liu, Shin-Huei; Chou, Yu-Hui; Chen, Shih-Ann; Fu, Yun-Ching; Kuo, Terry B J

2016-12-15

Autonomic imbalance with increased sympathetic and decreased parasympathetic activities is observed in patients after myocardial infarction (MI). We aimed to investigate sleep-related changed in autonomic regulation in left coronary artery (LCA) ligation rats. Wireless transmission of polysomnographic recording was performed in sham and LCA ligation male rats during normal daytime sleep with and without atenolol treatment. Spectral analyses of the electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet and paradoxical sleeps (QS, PS). Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability (HRV). EEG, EMG and HRV were recorded over 6h for consecutive 3days in all groups. In LCA ligation group, there were higher LF and LF/HF ratio on QS phase, but not AW and PS phases, compared to atenolol treated sham and LCA ligation groups, respectively. The HF component was not significantly changed on all groups in both sleep and awake phases. Sleep interruption was more frequent in LCA ligation rats compared to sham, and it was not found in LCA ligation with atenolol treatment group. Increased AW, PS and decreased QS time were noted in LCA ligation group, compared to sham and it was restored to baseline in LCA ligation with atenolol treatment group. Our results demonstrate significant sleep fragmentations with sympathetic hyperactivity during QS stages after MI, and atenolol could restore the autonomic dysfunction and sleep disturbance. The finding explains the cause of sleep-related fetal arrhythmia and sudden cardiac death after MI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient with Multiple System Atrophy: A Case Report].

PubMed

Konishi, Hanako; Mizota, Toshiyuki; Fukuda, Kazuhiko

2015-06-01

We report a case of persistent bilateral vocal cord paralysis which developed after spine surgery under general anesthesia in a patient with multiple system atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such as hoarseness before surgery. The surgery was performed smoothly under general anesthesia with endotracheal intubation. However, immediately after extubation, the patient developed severe upper airway obstruction and was re-intubated. Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal cord paralysis did not improve and she received tracheotomy on the 12th day after surgery. She also showed symptoms of autonomic nervous system dysfunction and cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative day 64. We discuss differential diagnosis of persistent vocal cord paralysis after general anesthesia, and anesthetic management of a patient with multiple system atrophy.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

PubMed

Lee, Kyung Yeon; Yeh, Hye-Ryun

2015-02-01

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm. Georg Thieme Verlag KG Stuttgart · New York.

Lipids of mitochondria.

PubMed

Horvath, Susanne E; Daum, Günther

2013-10-01

A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described. Copyright © 2013 Elsevier Ltd. All rights reserved.

Respiratory mechanics in brain injury: A review.

PubMed

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-02-04

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

NEONATAL ABSTINENCE SYNDROME: PHARMACOLOGIC STRATEGIES FOR THE MOTHER AND INFANT

PubMed Central

Kraft, Walter K.; Stover, Megan W.; Davis, Jonathan M.

2015-01-01

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet to be definitively established. Pharmacologic management of NAS is also highly variable and may include an opioid, barbiturate, and/or α-agonist. Genetic factors appear to be associated with the incidence and severity of NAS. Establishing pharmacogenetic risk factors for the development of NAS has the potential for creating opportunities for “personalized genomic medicine” and novel, individualized therapeutic interventions. PMID:26791055

Salivary Alpha-Amylase Activity Levels in Catatonic Schizophrenia Decrease after Electroconvulsive Therapy.

PubMed

Kanayama, Misako; Miyaoka, Tsuyoshi; Araki, Tomoko; Hayashida, Maiko; Hashioka, Sadayuki; Horiguchi, Jun

2018-01-01

Dysfunction of the autonomic nervous system (ANS) in schizophrenia has been detected by electrophysiological methods, but the underlying mechanisms remain unknown. Several studies have suggested that measuring salivary alpha-amylase activity levels is useful for evaluating the ANS activity and that sAA levels increase in schizophrenia and correlate with Brief Psychiatric Rating Scale (BPRS) scores. However, no study has examined the relationship between sAA activity levels and symptoms of schizophrenia with catatonic state. We present the case of a 59-year-old female with persistent catatonic schizophrenia treated by electroconvulsive therapy. We evaluated the ANS activity by measuring sAA activity levels before and after ECT, and we evaluated her symptoms using the BPRS and Bush-Francis Catatonia Rating Scale (BFCRS). ECT was highly effective and BPRS and BFCRS scores substantially decreased. sAA activity levels decreased from 125 kU/l to 33 kU/l. sAA activity levels could be a potential biomarker of schizophrenia with catatonic state.

Exercise, inflammation, and fatigue in cancer survivors

PubMed Central

LaVoy, Emily C.P.; Fagundes, Christopher P.; Dantzer, Robert

2016-01-01

Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue. PMID:26853557

Ecstatic Epileptic Seizures: A Glimpse into the Multiple Roles of the Insula

PubMed Central

Gschwind, Markus; Picard, Fabienne

2016-01-01

Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and “enhanced self-awareness.” They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n = 52); a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective, and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura. PMID:26924970

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed

Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

2016-01-01

Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed Central

Buchhorn, Reiner; Meint, Sebastian

2016-01-01

Introduction Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Results Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. Conclusion It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children—allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)—have the highest risk for ‘stress diseases’ such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children. PMID:27861527

Brain metabolites in autonomic regulatory insular sites in heart failure.

PubMed

Woo, Mary A; Yadav, Santosh K; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

2014-11-15

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.2 ppm, and MI at 3.56 ppm were assigned, peak areas were calculated, and metabolites were expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. Copyright © 2014 Elsevier B.V. All rights reserved.

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Brain Metabolites in Autonomic Regulatory Insular Sites in Heart Failure

PubMed Central

Woo, Mary A.; Yadav, Santosh K.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2014-01-01

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02ppm, Cr at 3.02ppm, Cho at 3.2ppm, and MI at 3.56ppm were assigned, peak areas calculated, and metabolites expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. PMID:25248953

Are patients with Parkinson’s disease blind to blindsight?

PubMed Central

Stebbins, Glenn; Schiltz, Christine; Goetz, Christopher G.

2014-01-01

In Parkinson’s disease, visual dysfunction is prominent. Visual hallucinations can be a major hallmark of late stage disease, but numerous visual deficits also occur in early stage Parkinson’s disease. Specific retinopathy, deficits in the primary visual pathway and the secondary ventral and dorsal pathways, as well as dysfunction of the attention pathways have all been posited as causes of hallucinations in Parkinson’s disease. We present data from patients with Parkinson’s disease that contrast with a known neuro-ophthalmological syndrome, termed ‘blindsight’. In this syndrome, there is an absence of conscious object identification, but preserved ‘guess’ of the location of a stimulus, preserved reflexive saccades and motion perception and preserved autonomical and expressive reactions to negative emotional facial expressions. We propose that patients with Parkinson’s disease have the converse of blindsight, being ‘blind to blindsight’. As such they preserve conscious vision, but show erroneous ‘guess’ localization of visual stimuli, poor saccades and motion perception, and poor emotional face perception with blunted autonomic reaction. Although a large data set on these deficits in Parkinson’s disease has been accumulated, consolidation into one specific syndrome has not been proposed. Focusing on neuropathological and physiological data from two phylogenetically old and subconscious pathways, the retino-colliculo-thalamo-amygdala and the retino-geniculo-extrastriate pathways, we propose that aberrant function of these systems, including pathologically inhibited superior colliculus activity, deficient corollary discharges to the frontal eye fields, dysfunctional pulvinar, claustrum and amygdaloid subnuclei of the amygdala, the latter progressively burdened with Lewy bodies, underlie this syndrome. These network impairments are further corroborated by the concept of the ‘silent amygdala’. Functionally being ‘blind to blindsight’ may facilitate the highly distinctive ‘presence’ or ‘passage’ hallucinations of Parkinson’s disease and can help to explain handicaps in driving capacities and dysfunctional ‘theory of mind’. We propose this synthesis to prompt refined neuropathological and neuroimaging studies on the pivotal nuclei in these pathways in order to better understand the networks underpinning this newly conceptualized syndrome in Parkinson’s disease. PMID:24764573

Somatic dysfunction and its association with chronic low back pain, back-specific functioning, and general health: results from the OSTEOPATHIC Trial.

PubMed

Licciardone, John C; Kearns, Cathleen M

2012-07-01

Somatic dysfunction is diagnosed by the presence of any of 4 TART criteria: tissue texture abnormality, asymmetry, restriction of motion, or tenderness. To measure the prevalence of somatic dysfunction in patients with chronic low back pain (LBP) and to study the associations of somatic dysfunction with LBP severity, back-specific functioning, and general health. Cross-sectional study nested within a randomized controlled trial. University-based study in Dallas-Fort Worth, Texas. A total of 455 adult research patients with non-specific chronic LBP. Somatic dysfunction in the lumbar, sacrum/pelvis, and pelvis/innominate regions, including key lesions representing severe somatic dysfunction. A 10-cm visual analog scale (VAS), the Roland-Morris Disability Questionnaire (RMDQ), and the Medical Outcomes Study Short Form-36 Health Survey (SF-36) were used to measure LBP severity, back-specific functioning, and general health, respectively. Severe somatic dysfunction was most prevalent in the lumbar (225 [49%]), sacrum/pelvis (129 [28%]), and pelvis/innominate (48 [11%]) regions. Only 30 patients (7%) had no somatic dysfunction in the lumbar, sacrum/pelvis, or pelvis/innominate regions. There were 4 statistically significant pairwise correlations for severe somatic dysfunction: thoracic (T) 10-12 with ribs; T10-12 with lumbar; lumbar with sacrum/pelvis; and sacrum/pelvis with pelvis/innominate. Having a key lesion in the lumbar region (ρ=0.80) or sacrum/pelvis region (ρ=0.71) was strongly correlated with the overall number of key lesions. There were no consistent demographic or clinical predictors of somatic dysfunction. The presence (vs absence) of severe somatic dysfunction in the lumbar region was associated with greater LBP severity (median VAS score, 4.7 vs 3.8, respectively; P=.003) and greater back-specific disability (median RMDQ score, 6 vs 4, respectively; P=.01). The presence (vs absence) of severe somatic dysfunction in the sacrum/pelvis region was associated with greater back-specific disability (median RMDQ score, 6 vs 5, respectively; P=.02) and poorer general health (median SF-36 score, 62 vs 72, respectively; P=.002). An increasing number of key lesions was associated with back-specific disability (P=.009) and poorer general health (P=.02). The present study demonstrates that somatic dysfunction, particularly in the lumbar and sacrum/pelvis regions, is common in patients with chronic LBP. Forthcoming extensions of the OSTEOPATHIC Trial will assess the efficacy of OMT according to baseline levels of somatic dysfunction.

Solving Autonomy Technology Gaps through Wireless Technology and Orion Avionics Architectural Principles

NASA Astrophysics Data System (ADS)

Black, Randy; Bai, Haowei; Michalicek, Andrew; Shelton, Blaine; Villela, Mark

2008-01-01

Currently, autonomy in space applications is limited by a variety of technology gaps. Innovative application of wireless technology and avionics architectural principles drawn from the Orion crew exploration vehicle provide solutions for several of these gaps. The Vision for Space Exploration envisions extensive use of autonomous systems. Economic realities preclude continuing the level of operator support currently required of autonomous systems in space. In order to decrease the number of operators, more autonomy must be afforded to automated systems. However, certification authorities have been notoriously reluctant to certify autonomous software in the presence of humans or when costly missions may be jeopardized. The Orion avionics architecture, drawn from advanced commercial aircraft avionics, is based upon several architectural principles including partitioning in software. Robust software partitioning provides "brick wall" separation between software applications executing on a single processor, along with controlled data movement between applications. Taking advantage of these attributes, non-deterministic applications can be placed in one partition and a "Safety" application created in a separate partition. This "Safety" partition can track the position of astronauts or critical equipment and prevent any unsafe command from executing. Only the Safety partition need be certified to a human rated level. As a proof-of-concept demonstration, Honeywell has teamed with the Ultra WideBand (UWB) Working Group at NASA Johnson Space Center to provide tracking of humans, autonomous systems, and critical equipment. Using UWB the NASA team can determine positioning to within less than one inch resolution, allowing a Safety partition to halt operation of autonomous systems in the event that an unplanned collision is imminent. Another challenge facing autonomous systems is the coordination of multiple autonomous agents. Current approaches address the issue as one of networking and coordination of multiple independent units, each with its own mission. As a proof-of-concept Honeywell is developing and testing various algorithms that lead to a deterministic, fault tolerant, reliable wireless backplane. Just as advanced avionics systems control several subsystems, actuators, sensors, displays, etc.; a single "master" autonomous agent (or base station computer) could control multiple autonomous systems. The problem is simplified to controlling a flexible body consisting of several sensors and actuators, rather than one of coordinating multiple independent units. By filling technology gaps associated with space based autonomous system, wireless technology and Orion architectural principles provide the means for decreasing operational costs and simplifying problems associated with collaboration of multiple autonomous systems.

Mood recognition in bipolar patients through the PSYCHE platform: preliminary evaluations and perspectives.

PubMed

Valenza, Gaetano; Gentili, Claudio; Lanatà, Antonio; Scilingo, Enzo Pasquale

2013-01-01

Bipolar disorders are characterized by a series of both depressive and manic or hypomanic episodes. Although common and expensive to treat, the clinical assessment of bipolar disorder is still ill-defined. In the current literature several correlations between mood disorders and dysfunctions involving the autonomic nervous system (ANS) can be found. The objective of this work is to develop a novel mood recognition system based on a pervasive, wearable and personalized monitoring system using ANS-related biosignals. The monitoring platform used in this study is the core sensing system of the personalized monitoring systems for care in mental health (PSYCHE) European project. It is comprised of a comfortable sensorized t-shirt that can acquire the inter-beat interval time series, the heart rate, and the respiratory dynamics for long-term monitoring during the day and overnight. In this study, three bipolar patients were followed for a period of 90 days during which up to six monitoring sessions and psychophysical evaluations were performed for each patient. Specific signal processing techniques and artificial intelligence algorithms were applied to analyze more than 120 h of data. Experimental results are expressed in terms of confusion matrices and an exhaustive descriptive statistics of the most relevant features is reported as well. A classification accuracy of about 97% is achieved for the intra-subject analysis. Such an accuracy was found in distinguishing relatively good affective balance state (euthymia) from severe clinical states (severe depression and mixed state) and is lower in distinguishing euthymia from the milder states (accuracy up to 88%). The PSYCHE platform could provide a viable decision support system in order to improve mood assessment in patient care. Evidences about the correlation between mood disorders and ANS dysfunctions were found and the obtained results are promising for an effective biosignal-based mood recognition. Copyright © 2012 Elsevier B.V. All rights reserved.

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy

PubMed Central

2014-01-01

Background The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology’s limited ability to interpret the child’s intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. Methods The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Results Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. Conclusions These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users. PMID:24607065

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy.

PubMed

Leung, Brian; Chau, Tom

2014-03-08

The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology's limited ability to interpret the child's intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users.

Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

PubMed

Moraes-Silva, Ivana Cinthya; Mostarda, Cristiano; Moreira, Edson Dias; Silva, Kleiton Augusto Santos; dos Santos, Fernando; de Angelis, Kátia; Farah, Vera de Moura Azevedo; Irigoyen, Maria Claudia

2013-03-15

High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology.

PubMed

van Bilsen, Marc; Patel, Hitesh C; Bauersachs, Johann; Böhm, Michael; Borggrefe, Martin; Brutsaert, Dirk; Coats, Andrew J S; de Boer, Rudolf A; de Keulenaer, Gilles W; Filippatos, Gerasimos S; Floras, John; Grassi, Guido; Jankowska, Ewa A; Kornet, Lilian; Lunde, Ida G; Maack, Christoph; Mahfoud, Felix; Pollesello, Piero; Ponikowski, Piotr; Ruschitzka, Frank; Sabbah, Hani N; Schultz, Harold D; Seferovic, Petar; Slart, Riemer H J A; Taggart, Peter; Tocchetti, Carlo G; Van Laake, Linda W; Zannad, Faiez; Heymans, Stephane; Lyon, Alexander R

2017-11-01

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future? © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Hereditary sensory and autonomic neuropathy types 4 and 5: Review and proposal of a new rehabilitation method.

PubMed

Yozu, Arito; Haga, Nobuhiko; Funato, Tetsuro; Owaki, Dai; Chiba, Ryosuke; Ota, Jun

2016-03-01

Although pain is unpleasant, it should serve as a reminder for individuals to avoid similar damaging incidents in the future. Hereditary sensory and autonomic neuropathy (HSAN) includes genetic disorders involving various sensory and autonomic dysfunctions. They are classified by the mode of inheritance, clinical features, and related genes. HSAN type 4 (HSAN-4) and type 5 (HSAN-5) are characterized by insensitivity to pain and thermal sensation. Further, HSAN-4 is accompanied by decreased sweating and intellectual disabilities. These characteristics of HSAN-4 and -5 result in many clinical features, such as pediatric, psychiatric, orthopedic, oral, dermatological, and ophthalmological problems. Orthopedic problems include destructive injuries such as multiple fractures and joint dislocation. Studies on gait have shown greater speed and higher heel contact angular velocity in HSAN-4 and -5 patients compared with controls. Studies on grasp-lift-holding tasks have shown higher grasp force and fluctuations in acceleration of the object. We believe that these findings represent outcomes of deficient motor learning. We propose a new rehabilitation method for patients with HSAN-4 and -5, with the aim of decreasing their destructive injuries. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Dyscirculatory encephalopathy in Chernobyl disaster clean-up workers (a 20-year study).

PubMed

Podsonnaya, I V; Shumakher, G I; Golovin, V A

2010-05-01

Results obtained over 20-years of following 536 Chernobyl clean-up workers and 436 control subjects are presented. Dyscirculatory encephalopathy developed more frequently in persons exposed to radiation at age 30 years. As compared with the control group, workers were characterized by early onset of disease, faster progression, stable symptomatology for 5-6 years, and further progression of disease in the form of autonomic dysfunction, psycho-organic syndrome, and epilepsy. Major strokes were also more common in clean-up workers.

Sexuality in patients with Parkinson's disease, Alzheimer's disease, and other dementias.

PubMed

Bronner, Gila; Aharon-Peretz, Judith; Hassin-Baer, Sharon

2015-01-01

Sexual dysfunction (SD) is common among patients with Parkinson's disease (PD), Alzheimer's disease (AD), and other dementias. Sexual functioning and well-being of patients with PD and their partners are affected by many factors, including motor disabilities, non-motor symptoms (e.g., autonomic dysfunction, sleep disturbances, mood disorders, cognitive abnormalities, pain, and sensory disorders), medication effects, and relationship issues. The common sexual problems are decreased desire, erectile dysfunction, difficulties in reaching orgasm, and sexual dissatisfaction. Hypersexuality is one of a broad range of impulse control disorders reported in PD, attributed to antiparkinsonian therapy, mainly dopamine agonists. Involvement of a multidisciplinary team may enable a significant management of hypersexuality. Data on SD in demented patients are scarce, mainly reporting reduced frequency of sex and erectile dysfunction. Treatment of SD is advised at an early stage. Behavioral problems, including inappropriate sexual behavior (ISB), are distressing for patients and their caregivers and may reflect the prevailing behavior accompanying dementia (disinhibition or apathy associated with hyposexuality). The neurobiologic basis of ISB is still only vaguely understood but assessment and intervention are recommended as soon as ISB is suspected. Management of ISB in dementia demands a thorough evaluation and understanding of the behavior, and can be treated by non-pharmacologic and pharmacologic interventions. © 2015 Elsevier B.V. All rights reserved.

Idiopathic orthostatic intolerance and postural tachycardia syndromes

NASA Technical Reports Server (NTRS)

Jacob, G.; Biaggioni, I.; Robertson, D. (Principal Investigator)

1999-01-01

Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to orthostatic intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling orthostatic intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to orthostatic intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.

The head and neck discomfort of autonomic failure: an unrecognized aetiology of headache

NASA Technical Reports Server (NTRS)

Robertson, D.; Kincaid, D. W.; Haile, V.; Robertson, R. M.

1994-01-01

Information concerning the frequency, severity, character, location, duration, diurnal pattern of headache and ancillary symptoms were obtained in 25 patients with autonomic failure and 44 control subjects. Precipitating and ameliorating factors were identified. Autonomic failure patients had more head and neck discomfort than controls. Their discomfort was much more likely to localize in the occiput, nape of the neck and shoulder, compared with controls. There was a greater tendency for the discomfort to occur in the morning and after meals. It was sometimes less than 5 min in duration and was often associated with dimming, blurring, or tunnelling of vision. It was provoked by upright posture and relieved by lying down. Patients with severe autonomic failure and orthostatic hypotension often present with a posture-dependent headache or neck pain. Because the relationship of these symptoms to posture is often not recognized, the fact that these findings may signal an underlying autonomic disorder is underappreciated, and the opportunity to consider this aetiology for the headache may be missed.

Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications.

PubMed

Cho, Y H; Craig, M E; Januszewski, A S; Benitez-Aguirre, P; Hing, S; Jenkins, A J; Donaghue, K C

2017-04-01

To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA 1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. Skin autofluorescence was significantly associated with age (R 2 = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA 1c (R 2 = 0.32; P < 0.001) and HbA 1c over the previous 2.5-10 years (R 2 = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R 2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R 2 = 0.11; P = 0.006). Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications. © 2016 Diabetes UK.

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.

PubMed

Barclay, Sarah F; Rand, Casey M; Borch, Lauren A; Nguyen, Lisa; Gray, Paul A; Gibson, William T; Wilson, Richard J A; Gordon, Paul M K; Aung, Zaw; Berry-Kravis, Elizabeth M; Ize-Ludlow, Diego; Weese-Mayer, Debra E; Bech-Hansen, N Torben

2015-08-25

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation.

Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

PubMed Central

Díez-Noguera, Antoni

2018-01-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year. Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer. Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME. PMID:29874259

Evaluation of Cardiovascular Risk Factors in the Wistar Audiogenic Rat (WAR) Strain

PubMed Central

Fazan, Rubens; Silva, Carlos Alberto A.; Oliveira, José Antônio Cortes; Salgado, Helio Cesar; Montano, Nicola; Garcia-Cairasco, Norberto

2015-01-01

Introduction Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. Methods We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. Results Basal RR interval (RRi) was similar between WAR and Wistar rats (188±5 vs 199±6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92±3 vs 115±5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2±0.6 vs 5.6±1 mmHg) and volume (137±9 vs 68±9 μL) as well as lower rate of increase in ventricular pressure (5266±602 vs 7320±538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014±780 vs -7766±998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078±0.011 vs 0.036±0.011 mmHg.μL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. Conclusions The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy. PMID:26029918

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.

PubMed

Onorati, Francesco; Regalia, Giulia; Caborni, Chiara; Migliorini, Matteo; Bender, Daniel; Poh, Ming-Zher; Frazier, Cherise; Kovitch Thropp, Eliana; Mynatt, Elizabeth D; Bidwell, Jonathan; Mai, Roberto; LaFrance, W Curt; Blum, Andrew S; Friedman, Daniel; Loddenkemper, Tobias; Mohammadpour-Touserkani, Fatemeh; Reinsberger, Claus; Tognetti, Simone; Picard, Rosalind W

2017-11-01

New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The NASA/Army Autonomous Rotorcraft Project

NASA Technical Reports Server (NTRS)

Whalley, M.; Freed, M.; Takahashi, M.; Christian, D.; Patterson-Hine, A.; Schulein, G.; Harris, R.

2002-01-01

An overview of the NASA Ames Research Center Autonomous Rotorcraft Project (ARP) is presented. The project brings together several technologies to address NASA and US Army autonomous vehicle needs, including a reactive planner for mission planning and execution, control system design incorporating a detailed understanding of the platform dynamics, and health monitoring and diagnostics. A candidate reconnaissance and surveillance mission is described. The autonomous agent architecture and its application to the candidate mission are presented. Details of the vehicle hardware and software development are provided.

Investigating the neurodevelopmental mediators of aggression in children with a history of child maltreatment:An exploratory field study.

PubMed

Dileo, J F; Brewer, W; Northam, E; Yucel, M; Anderson, V

2017-08-01

Maltreatment of children is a chronic community problem that increases the risk of future aggression. Despite several decades of research highlighting this relationship, few studies have explored the potential neuropsychological deficits that are likely to mediate it. This exploratory study aimed to examine how child maltreatment may be associated with aggression via impairment in the developing prefrontal-limbic-autonomic pathways that are implicated in neuropsychological models of aggression. Furthermore, it aimed to investigate the relationship between child maltreatment and both reactive and proactive aggression subtypes. To investigate this non-invasively in an at-risk population, children with a documented protective care history (n = 20) and a community control group (n = 30), aged between 6 and 12 years, were compared on measures of cardiovascular functioning, affect regulation and cognitive functioning aligned with this neuropsychological model. Whilst no group differences were found on cardiovascular functioning (i.e., resting heart rate, heart rate reactivity, heart rate variability), the protective care group performed significantly worse on measures of affect regulation and cognitive functioning (i.e., global intelligence, executive functioning, smell identification and social cognition). The relationship between child maltreatment and aggression was mediated by executive dysfunction and affect dysregulation but not global IQ, social cognition or olfactory identification. The results suggest that interventions targeting aggression in maltreated children will benefit from clinical assessment and psychological strategies that address the executive dysfunction and affect dysregulation that has been associated with this clinical outcome.

Evaluation in an Autonomous Learning Scheme. Melanges Pedagogiques, 1977.

ERIC Educational Resources Information Center

Henner-Stanchina, C.; Holec, H.

This document consists of a discussion of the place and nature of evaluation within the autonomous learning scheme developed by the Centre de Recherches et d'Applications Pedagogiques en Langues (C.R.A.P.E.L.). The center's commitment to the development of an autonomous learning scheme dates back several years. It is the outcome of an attempt to…

Exploring the Relationship of Autonomic and Endocrine Activity with Social Functioning in Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Smeekens, I.; Didden, R.; Verhoeven, E. W. M.

2015-01-01

Several studies indicate that autonomic and endocrine activity may be related to social functioning in individuals with autism spectrum disorder (ASD), although the number of studies in adults is limited. The present study explored the relationship of autonomic and endocrine activity with social functioning in young adult males with ASD compared…

Vestibular influences on autonomic cardiovascular control in humans

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Costa, F.; Kaufmann, H.; Robertson, D. (Principal Investigator)

1998-01-01

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Swimming pool exposure is associated with autonomic changes and increased airway reactivity to a beta-2 agonist in school aged children: A cross-sectional survey.

PubMed

Cavaleiro Rufo, João; Paciência, Inês; Silva, Diana; Martins, Carla; Madureira, Joana; Oliveira Fernandes, Eduardo de; Padrão, Patrícia; Moreira, Pedro; Delgado, Luís; Moreira, André

2018-01-01

Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. A total of 858 children enrolled a cross sectional survey. Spirometry and airway reversibility to beta-2 agonist, skin-prick-tests and exhaled nitric oxide measurements were performed. Pupillometry was used to evaluate autonomic nervous function. Children were classified as current swimmers (CS), past swimmers (PS) and non-swimmers (NS), according to the amount of swimming practice. Current swimmers group had significantly lower maximum and average pupil constriction velocities when compared to both PS and NS groups (3.8 and 5.1 vs 3.9 and 5.3 vs 4.0 and 5.4 mm/s, p = 0.03 and p = 0.01, respectively). Moreover, affinity to the beta-2 agonist and levels of exhaled nitric oxide were significantly higher in CS when compared to NS (70 vs 60 mL and 12 vs 10 ppb, p<0.01 and p = 0.03, respectively). A non-significant trend for a higher risk of asthma, atopic eczema and allergic rhinitis was found with more years of swimming practice, particularly in atopic individuals (β = 1.12, 1.40 and 1.31, respectively). After case-case analysis, it was possible to observe that results were not influenced by the inclusion of individuals with asthma. Concluding, swimming pool attendance appears to be associated with autonomic changes and increased baseline airway smooth muscle constriction even in children without asthma.

Cardiac autonomic regulation is disturbed in children with euthyroid Hashimoto thyroiditis.

PubMed

Kilic, Ayhan; Gulgun, Mustafa; Tascilar, Mehmet Emre; Sari, Erkan; Yokusoglu, Mehmet

2012-03-01

Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common form of thyroiditis in childhood. Previous studies have found autonomic dysfunction of varying magnitude in patients with autoimmune diseases, which is considered a cardiovascular risk factor. We aimed to evaluate the heart rate variability (HRV), a measure of cardiac autonomic modulation, in children with euthyroid Hashimoto thyroiditis (eHT). The study included 32 patients with eHT (27 girls and 5 boys; mean age 11 ± 4.1 years, range 8-16; body mass index 0.47 ± 0.69 kg/m(2)), as judged by normal or minimally elevated serum TSH levels (normal range: 0.34-5.6 mIU/l) and normal levels of free thyroid hormones (FT4 and FT3) and 38 euthyroid age-matched controls. Patients with eHT and control subjects underwent physical examination and 24-hour ambulatory ECG monitoring. Time-domain parameters of HRV were evaluated for cardiac autonomic functions. Children with eHT displayed significantly lower values of time-domain parameters of SDANN (standard deviation of the averages of NN intervals), RMSSD (square root of the mean of the sum of the squares of differences between adjacent NN intervals), NN50 counts (number of pairs of adjacent NN intervals differing by more than 50 ms) and PNN50 (NN50 count divided by the total number of all NN intervals) for each 5-min interval, compared to healthy controls (p < 0.05 for each), indicating the decreased beat-to-beat variation of heart rate. In conclusion, eHT is associated with disturbed autonomic regulation of heart rate. Hence, the children with eHT are at higher risk for developing cardiovascular diseases.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Type 2 diabetes and cardiac autonomic neuropathy screening using dynamic pupillometry

PubMed Central

Lerner, Alana G.; Bernabé-Ortiz, Antonio; Ticse, Ray; Hernandez, Arturo; Huaylinos, Yvonne; Pinto, Miguel E.; Málaga, Germán; Checkley, William; Gilman, Robert H.; Miranda, J. Jaime

2015-01-01

Aim To determine if changes in pupillary response are useful as a screening tool for diabetes and to assess whether pupillometry is associated with cardiac autonomic neuropathy. Methods We conducted a cross-sectional study with participants drawn from two settings: a hospital and a community site. At the community site, individuals with newly diagnosed diabetes as well as a random sample of control individuals without diabetes, confirmed by oral glucose tolerance test, were selected. Participants underwent an LED light stimulus test and eight pupillometry variables were measured. Outcomes were diabetes, defined by oral glucose tolerance test, and cardiac autonomic dysfunction, determined by a positive readout on two of four diagnostic tests: heart rate response to the Valsalva manoeuvre; orthostatic hypotension; 30:15 ratio; and expiration-to-inspiration ratio. The area under the curve, best threshold, sensitivity and specificity of each pupillometry variable was calculated. Results Data from 384 people, 213 with diabetes, were analysed. The mean (±SD) age of the people with diabetes was 58.6 (±8.2) years and in the control subjects it was 56.1 (±8.6) years. When comparing individuals with and without diabetes, the amplitude of the pupil reaction had the highest area under the curve [0.69 (sensitivity: 78%; specificity: 55%)]. Cardiac autonomic neuropathy was present in 51 of the 138 people evaluated (37.0%; 95% CI 28.8–45.1). To diagnose cardiac autonomic neuropathy, two pupillometry variables had the highest area under the curve: baseline pupil radius [area under the curve: 0.71 (sensitivity: 51%; specificity: 84%)], and amplitude of the pupil reaction [area under the curve: 070 (sensitivity: 82%; specificity: 55%)]. Conclusions Pupillometry is an inexpensive technique to screen for diabetes and cardiac autonomic neuropathy, but it does not have sufficient accuracy for clinical use as a screening tool. PMID:25761508

Type 2 diabetes and cardiac autonomic neuropathy screening using dynamic pupillometry.

PubMed

Lerner, A G; Bernabé-Ortiz, A; Ticse, R; Hernandez, A; Huaylinos, Y; Pinto, M E; Málaga, G; Checkley, W; Gilman, R H; Miranda, J J

2015-11-01

To determine if changes in pupillary response are useful as a screening tool for diabetes and to assess whether pupillometry is associated with cardiac autonomic neuropathy. We conducted a cross-sectional study with participants drawn from two settings: a hospital and a community site. At the community site, individuals with newly diagnosed diabetes as well as a random sample of control individuals without diabetes, confirmed by oral glucose tolerance test, were selected. Participants underwent an LED light stimulus test and eight pupillometry variables were measured. Outcomes were diabetes, defined by oral glucose tolerance test, and cardiac autonomic dysfunction, determined by a positive readout on two of four diagnostic tests: heart rate response to the Valsalva manoeuvre; orthostatic hypotension; 30:15 ratio; and expiration-to-inspiration ratio. The area under the curve, best threshold, sensitivity and specificity of each pupillometry variable was calculated. Data from 384 people, 213 with diabetes, were analysed. The mean (±sd) age of the people with diabetes was 58.6 (±8.2) years and in the control subjects it was 56.1 (±8.6) years. When comparing individuals with and without diabetes, the amplitude of the pupil reaction had the highest area under the curve [0.69 (sensitivity: 78%; specificity: 55%)]. Cardiac autonomic neuropathy was present in 51 of the 138 people evaluated (37.0%; 95% CI 28.8-45.1). To diagnose cardiac autonomic neuropathy, two pupillometry variables had the highest area under the curve: baseline pupil radius [area under the curve: 0.71 (sensitivity: 51%; specificity: 84%)], and amplitude of the pupil reaction [area under the curve: 0.70 (sensitivity: 82%; specificity: 55%)]. Pupillometry is an inexpensive technique to screen for diabetes and cardiac autonomic neuropathy, but it does not have sufficient accuracy for clinical use as a screening tool. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Autonomic dysfunction predicts poor physical improvement after cardiac rehabilitation in patients with heart failure.

PubMed

Compostella, Leonida; Nicola, Russo; Tiziana, Setzu; Caterina, Compostella; Fabio, Bellotto

2014-11-01

Cardiac autonomic dysfunction, clinically expressed by reduced heart rate variability (HRV), is present in patients with congestive heart failure (CHF) and is related to the degree of left ventricular dysfunction. In athletes, HRV is an indicator of ability to improve performance. No similar data are available for CHF. The aim of this study was to assess whether HRV could predict the capability of CHF patients to improve physical fitness after a short period of exercise-based cardiac rehabilitation (CR). This was an observational, non-randomized study, conducted on 57 patients with advanced CHF, admitted to a residential cardiac rehabilitation unit 32 ± 22 days after an episode of acute heart failure. Inclusion criteria were sinus rhythm, stable clinical conditions, no diabetes and ejection fraction ≤ 35%. HRV (time-domain) and mean and minimum heart rate (HR) were evaluated using 24-h Holter at admission. Patients' physical fitness was evaluated at admission by 6-minute walking test (6MWT) and reassessed after two weeks of intensive exercise-based CR. Exercise capacity was evaluated by a symptom-limited cardiopulmonary exercise test (CPET). Patients with very depressed HRV (SDNN 55.8 ± 10.0 ms) had no improvement in their walking capacity after short CR, walked shorter absolute distances at final 6MWT (348 ± 118 vs. 470 ± 109 m; P = 0.027) and developed a peak-VO2 at CPET significantly lower than patients with greater HRV parameters (11.4 ± 3.7 vs. an average > 16 ± 4 mL/kg/min). Minimum HR, but not mean HR, showed a negative correlation (ρ = -0.319) with CPET performance. In patients with advanced CHF, depressed HRV and higher minimum HR were predictors of poor working capacity after a short period of exercise-based CR. An individualized and intensive rehabilitative intervention should be considered for these patients.

Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.

PubMed

Lincevicius, Gisele S; Shimoura, Caroline G; Nishi, Erika E; Perry, Juliana C; Casarini, Dulce E; Gomes, Guiomar N; Bergamaschi, Cássia T; Campos, Ruy R

2015-09-01

Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood. The current study evaluated whether aldosterone contributes to cardiovascular and renal dysfunction in the 2 kidney-1 clip (2K1C) model. Mean arterial pressure (MAP) and baroreceptor reflex for control of the heart rate were evaluated in 2K1C treated or not treated with spironolactone (200mg/kg/day, 7 days). Tonic and reflex control of renal sympathetic nerve activity (rSNA) were assessed in urethane-anaesthetized rats. Plasma renin activity (PRA), kidney renin protein expression, renal injury, and central AT1 receptor protein expression were assessed. Spiro reduced MAP (198±4 vs. 170±9mm Hg; P < 0.05), normalized rSNA (147±9 vs. 96±10 pps; P < 0.05), and increased renal baroreceptor reflex sensitivity in the 2K1C rats. Spiro reduced α-smooth muscle actin expression in the nonclipped kidney in the 2K1C group (5±0.6 vs. 1.1±0.2%; P < 0.05). There was no change in PRA; however, a decrease in renin protein expression in the nonclipped kidney was found in the 2K1C treated group (217±30 vs. 160±19%; P < 0.05). Spiro treatment decreased AT1 receptor in the central nervous system (CNS) only in 2K1C rats (138±10 vs. 84±12%; P < 0.05). Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Autonomic dysfunction in patients with Brugada syndrome: further biochemical evidence of altered signaling pathways.

PubMed

Paul, Matthias; Meyborg, Matthias; Boknik, Peter; Gergs, Ulrich; Schmitz, Wilhelm; Breithardt, Günter; Wichter, Thomas; Neumann, Joachim

2011-09-01

In patients with Brugada syndrome (BrS), life-threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS. Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5'monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G-proteins (G(i1,2) α), troponin-I (TNI), and phosphorylated TNI were analyzed. Levels of NET, G(i1,2) α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations. The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β-adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

Oxidative stress is associated with decreased heart rate variability in patients with chronic kidney disease.

PubMed

Fadaee, Shannon B; Beetham, Kassia S; Howden, Erin J; Stanton, Tony; Isbel, Nicole M; Coombes, Jeff S

2017-09-01

Elevated oxidative stress and reduced heart rate variability (HRV) is prevalent in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Previous studies have identified a positive association between elevated oxidative stress and autonomic dysfunction, however this relationship has not yet been investigated in the CKD population. Plasma was collected from 78 patients with stage 3-4 CKD (estimated glomerular filtration rate 25-60 ml/min/1.73 m 2 ) for the assessment of oxidative stress, including plasma total F2-isoprostanes, glutathione peroxidase activity and total antioxidant capacity. Time and frequency HRV parameters were measured from a three lead electrocardiogram. Participants with elevated F2-isoprostanes had reduced HRV compared to patients with normal levels of F2-isoprostanes. A number of HRV parameters were found to be inversely correlated with F2-isoprostanes in all CKD patients, including SDNN (r = -0.337; P < 0.01), VLF (r = -0.281, P = 0.01), LF (r = -0.315, P < 0.01) and total power (r = -0.288, P = 0.01). Multiple linear regression found F2-isoprostanes to be an independent predictor of SDNN (r 2  = 0.287, β = -0.272, P = 0.01). Oxidative stress is significantly and independently associated with HRV in patients with CKD. Identifying oxidative stress in the pathogenesis of autonomic dysfunction may help target therapeutic strategies.

[Relationship between blood pressure, heart rate and cardiac autonomic dysfunction in non-diabetic obese patients].

PubMed

Banu, I; Nguyen, M T; Hamo-Tchatchouang, E; Cosson, E; Valensi, P

2015-06-01

Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes. We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated. The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (< or ≥ 75 bpm). Age was similar in the four groups. Systolic (P=0.05), diastolic (P<0.005) and mean BP (P<0.001) differed significantly between the 4 groups, and was the highest in the group of patients who had 2 or 3 abnormal tests and HR ≥ 75 bpm. Matsuda index differed across the groups (P=0.018) and was the lowest in this group. These data indicate that among overweight or obese patients with a defect in cardiac vagal activity BP is elevated only in those with a high heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Wearable technology and ECG processing for fall risk assessment, prevention and detection.

PubMed

Melillo, Paolo; Castaldo, Rossana; Sannino, Giovanna; Orrico, Ada; de Pietro, Giuseppe; Pecchia, Leandro

2015-01-01

Falls represent one of the most common causes of injury-related morbidity and mortality in later life. Subjects with cardiovascular disorders (e.g., related to autonomic dysfunctions and postural hypotension) are at higher risk of falling. Autonomic dysfunctions increasing the risk of falling in the short and mid-term could be assessed by Heart Rate Variability (HRV) extracted by electrocardiograph (ECG). We developed three trials for assessing the usefulness of ECG monitoring using wearable devices for: risk assessment of falling in the next few weeks; prevention of imminent falls due to standing hypotension; and fall detection. Statistical and data-mining methods are adopted to develop classification and regression models, validated with the cross-validation approach. The first classifier based on HRV features enabled to identify future fallers among hypertensive patients with an accuracy of 72% (sensitivity: 51.1%, specificity: 80.2%). The regression model to predict falls due to orthostatic dropdown from HRV recorded before standing achieved an overall accuracy of 80% (sensitivity: 92%, specificity: 90%). Finally, the classifier to detect simulated falls using ECG achieved an accuracy of 77.3% (sensitivity: 81.8%, specificity: 72.7%). The evidence from these three studies showed that ECG monitoring and processing could achieve satisfactory performances compared to other system for risk assessment, fall prevention and detection. This is interesting as differently from other technologies actually employed to prevent falls, ECG is recommended for many other pathologies of later life and is more accepted by senior citizens.

A novel cell-based assay for inhibitory anti-muscarinic type 3 receptor antibodies in primary Sjögren's syndrome.

PubMed

Bastian, Isabell; Gordon, Tom P; Jackson, Michael W

2015-12-01

Inhibitory autoantibodies acting at the muscarinic acetylcholine receptor type 3 (M3R) are postulated to mediate autonomic dysfunction, including decreased salivary and lacrimal gland output and extra-glandular manifestations, in patients with primary Sjögren's syndrome. However, the contention that anti-M3R antibodies are pathogenic in patients remains untested, due to a lack of assays both sophisticated enough to detect inhibitory anti-M3R antibodies yet suitable for screening large patient cohorts. In the current study, we have established a cell-based bioassay of M3R activity, based on dual transfection of the M3R and a luciferase reporter gene. The bioassay is capable of capturing real-time agonist-mediated signalling of the M3R, which is inhibited specifically by patient IgG that have previously been demonstrated to have anti-M3R activity. The assay can be run in multi-well culture plates, and analysed using simple luminescence readers. As such, the new bioassay incorporating M3R-mediated luciferase transduction is the first assay adaptable to common diagnostic platforms that is capable of determining the presence in patient serum of functionally active anti-M3R autoantibodies. The new bioassay should prove useful for large cohort screening studies aiming to correlate the presence in patients of inhibitory anti-M3R antibodies with symptoms of both glandular and extra-glandular autonomic dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

Diurnal and nocturnal cardiovascular variability and heart rate arousal response in idiopathic hypersomnia.

PubMed

Sforza, Emilia; Roche, Frédéric; Barthélémy, Jean Claude; Pichot, Vincent

2016-08-01

Autonomic nervous system dysfunction has been described in narcolepsy with cataplexy affecting sympathetic functions. In this study we analyzed whether altered diurnal and nocturnal cardiovascular control is present in idiopathic hypersomnia (IH). Fourteen drug-free patients aged 26.2 ± 7 years and 14 age-matched controls were examined. Clinical data, 24-h polysomnography, heart rate (HR) variability, and the HR response to spontaneous arousal were available. Sleep macrostructure was comparable between controls and patients, with the latter having significantly longer sleep time, a higher number of sleep cycles (p < 0.0001), and low sleep efficiency (p < 0.01). The HR variability indices did not differ between groups, except for the rise of high frequency (HF) and HFnu in patients (p < 0.05) associated with blunted sympathetic indices (p < 0.01). These parasympathetic alterations were present for light, slow wave, and rapid eye-movement sleep and persisted for all sleep cycles. Compared to controls, the HR arousal response was significantly higher (p < 0.01) in patients starting before the arousal onset and persisting into the post-arousal period. In IH patients a dysfunction of the parasympathetic activity during awake and sleep and an altered autonomic response to arousals are present. These findings suggest an impaired parasympathetic function that may explain some vegetative symptoms present in this type of central hypersomnia. Copyright © 2016 Elsevier B.V. All rights reserved.

Effectiveness of bomber deployed autonomous airborne vehicles in finding rail mobile SS-24s

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abey, A.E.; Erickson, S.A.; Norquist, P.D.

1990-08-01

Computer simulation predictions of the effectiveness of autonomous airborne vehicles in finding rail mobile SS-24s are presented. Effectiveness is discussed for several autonomous airborne vehicle endurances and survivabilities for the search area southwest of Moscow. The effect of where the Soviets place the SS-24s on the rail network was also investigated. The simulation predicts significant variations in the ability of a multi-autonomous airborne vehicle system to find SS-24s with these parameters. 12 figs., 1 tab.

Autonomic headache with autonomic seizures: a case report.

PubMed

Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

2006-10-01

The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

SMN is required for sensory-motor circuit function in Drosophila

PubMed Central

Imlach, Wendy L.; Beck, Erin S.; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D.

2012-01-01

Summary Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous Survival Motor Neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to non-autonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K+ channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease. PMID:23063130

Electrocardiographic abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major.

PubMed

Kolios, Marios; Korantzopoulos, Panagiotis; Vlahos, Antonios P; Kapsali, Eleni; Briasoulis, Evangelos; Goudevenos, John A

2016-10-15

There seems to be a significant arrhythmia burden in β-thalassemia major (TM) patients without overt cardiomyopathy. Apart from conventional electrocardiographic (ECG) and arrhythmic risk markers we studied novel markers of ventricular repolarization and autonomic imbalance both at rest and after exercise testing. We studied 47 adult TM patients without systolic heart failure and 47 age and sex-matched healthy control subjects. The median age of the studied population was 36 [32-43] years, 57% men. Baseline demographic and clinical characteristics were recorded while 12-lead electrocardiograms, 24-hour ECG Holter recordings, and treadmill exercise stress tests were analyzed. TM patients exhibited increased QTc intervals in both 12-lead ECG recordings and in 24-hour Holter recordings. In addition, they had increased indexes of ventricular repolarization heterogeneity such as QT dispersion, and T peak-to-end/QT ratios. Furthermore, TM patients had decreased indexes of heart rate variability while the heart rate recovery after exercise was significantly attenuated compared to controls. Also, they had increased P wave and QRS duration while the QRS fragmentation was very prevalent. Finally, premature atrial extrasystoles and paroxysmal atrial fibrillation episodes were more frequent in TM patients. TM patients with preserved left ventricular systolic function have several ECG abnormalities including alterations in ventricular depolarization and repolarization. Also, cardiac autonomic dysfunction is evident in 24-hour ECG monitoring as well as in the recovery phase after exercise testing. The prognostic value of specific arrhythmic risk indexes in this setting remains to be elucidated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HIV-1-Tat excites cardiac parasympathetic neurons of nucleus ambiguus and triggers prolonged bradycardia in conscious rats

PubMed Central

Brailoiu, Eugen; Deliu, Elena; Sporici, Romeo A.; Benamar, Khalid

2014-01-01

The mechanisms of autonomic imbalance and subsequent cardiovascular manifestations in HIV-1-infected patients are poorly understood. We report here that HIV-1 transactivator of transcription (Tat, fragment 1–86) produced a concentration-dependent increase in cytosolic Ca2+ in cardiac-projecting parasympathetic neurons of nucleus ambiguus retrogradely labeled with rhodamine. Using store-specific pharmacological agents, we identified several mechanisms of the Tat-induced Ca2+ elevation: 1) lysosomal Ca2+ mobilization, 2) Ca2+ release via inositol 1,4,5-trisphosphate-sensitive endoplasmic reticulum pools, and 3) Ca2+ influx via transient receptor potential vanilloid type 2 (TRPV2) channels. Activation of TRPV2, nonselective cation channels, induced a robust and prolonged neuronal membrane depolarization, thus triggering an additional P/Q-mediated Ca2+ entry. In vivo microinjection studies indicate a dose-dependent, prolonged bradycardic effect of Tat administration into the nucleus ambiguus of conscious rats, in which neuronal TRPV2 played a major role. Our results support previous studies, indicating that Tat promotes bradycardia and, consequently, may be involved in the QT interval prolongation reported in HIV-infected patients. In the context of an overall HIV-dependent autonomic dysfunction, these Tat-mediated mechanisms may account for the higher prevalence of sudden cardiac death in HIV-1-infected patients compared with general population with similar risk factors. Our results may be particularly relevant in view of the recent findings that significant Tat levels can still be identified in the cerebrospinal fluid of HIV-infected patients with viral load suppression due to efficient antiretroviral therapy. PMID:24694382

The unexplored relationship between urinary tract infections and the autonomic nervous system.

PubMed

Hibbing, Michael E; Conover, Matt S; Hultgren, Scott J

2016-10-01

Urinary tract infections (UTIs), the majority of which are caused by uropathogenic E. coli (UPEC), are extremely common infections that preferentially effect women. Additional complicating factors, such as catheterization, diabetes, and spinal cord injuries can increase the frequency and severity of UTIs. The rise of antimicrobial resistant uropathogens and the ability of this disease to chronically recur make the development of alternative preventative and therapeutic modalities a priority. The major symptoms of UTIs, urgency, frequency, and dysuria, are readouts of the autonomic nervous system (ANS) and the majority of the factors that lead to complicated UTIs have been shown to impact ANS function. This review summarizes the decades' long efforts to understand the molecular mechanisms of the interactions between UPEC and the host, with a particular focus on the recent findings revealing the molecular, bacteriological, immunological and epidemiological complexity of pathogenesis. Additionally, we describe the progress that has been made in: i) generating vaccines and anti-virulence compounds that prevent and/or treat UTI by blocking bacterial adherence to urinary tract tissue and; and ii) elucidating the mechanism by which anti-inflammatories are able to alleviate symptoms and improve disease prognosis. Finally, the potential relationships between the ANS and UTI are considered throughout. While these relationships have not been experimentally explored, the known interactions between numerous UTI characteristics (symptoms, complicating factors, and inflammation) and ANS function suggest that UTIs are directly impacting ANS stimulation and that ANS (dys)function may alter UTI prognosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

PubMed

Marques, Ana; Dutheil, Frédéric; Durand, Elodie; Rieu, Isabelle; Mulliez, Aurélien; Fantini, Maria Livia; Boirie, Yves; Durif, Franck

2018-05-31

To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l -1 ; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physical Activity and Heart Rate Variability in Older Adults: The Cardiovascular Health Study

PubMed Central

Soares-Miranda, Luisa; Sattelmair, Jacob; Chaves, Paulo; Duncan, Glen; Siscovick, David S; Stein, Phyllis K; Mozaffarian, Dariush

2014-01-01

Background Cardiac mortality and electrophysiologic dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity (PA) among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults. Methods and Results We evaluated serial longitudinal measures of both PA and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard-deviation-of-all-normal-to-normal-intervals (SDNN, p-trend=0.009, 0.02, 0.06, respectively) and ultra-low-frequency-power (p-trend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with higher short-term-fractal-scaling-exponent (p-trend=0.003) and lower Poincare ratio (p-trend=0.02), markers of less erratic sinus patterns. Conclusions Greater total leisure-time activity, as well as walking alone, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual PA later in life. PMID:24799513

Sleep in heart failure.

PubMed

Naughton, Matthew T; Lorenzi-Filho, Geraldo

2009-01-01

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.

Dysautonomic responses during percutaneous carotid intervention: principles of physiology and management.

PubMed

Bujak, Marcin; Stilp, Erik; Meller, Stephanie M; Cal, Nicolas; Litsky, Jason; Setaro, John F; Mena, Carlos

2015-02-01

Percutaneous carotid artery stenting (CAS) has emerged as a less invasive alternative to carotid endarterectomy for the treatment of carotid atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular complications; however, carotid artery stenting-related dysautonomia (CAS-D) (hypertension, hypotension, and bradycardia) is the most frequently reported problem occurring in the periprocedural period. Alterations in autonomic homeostasis result from baroreceptor stimulation, which occurs particularly at the time of balloon inflation in the region of the carotid sinus. The response can be profound enough to induce asystole or even complete cessation of postganglionic sympathetic nerve activity. Frequency and factors predisposing a patient to CAS-D have been investigated in several studies; however, there are significant discrepancies in results among reports. Lack of consistent findings may arise from using different methods and definitions, as well as other factors discussed in detail in this review. Furthermore, a correlation of CAS-D with short and long-term outcomes has been investigated only in small and mostly retrospective studies, explaining why its prognostic significance remains uncertain. In this manuscript, we have focused on risk factors, pathophysiology and management of periprocedural autonomic dysfunction. As there is no standardized approach to the treatment of CAS-D, we present an algorithm for the periprocedural management of patients undergoing CAS. The proposed algorithm was developed based on our procedural experience as well as data from the available literature. The Yale Algorithm was successfully implemented at our institution and we are currently collecting data for short- and long-term safety. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Mental health screening in women with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula in western Uganda.

PubMed

Krause, Hannah G; Hall, Barbara A; Ng, Shu-Kay; Natukunda, Harriet; Singasi, Isaac; Goh, Judith T W

2017-06-01

High levels of mental health dysfunction have been identified in women with genital tract fistula. The aim of this study was to use the General Health Questionnaire-28 (GHQ-28) to screen women in western Uganda with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula for risk of mental health dysfunction. Women undergoing surgery for severe pelvic organ prolapse, chronic fourth-degree obstetric tear, and genital tract fistula were interviewed using the GHQ-28 to screen for the risk of mental health dysfunction. A total of 125 women completed the GHQ-28, including 22 with pelvic organ prolapse, 47 with fourth-degree obstetric tear, 21 with genital tract fistula, and 35 controls. Nearly all women with these serious gynaecological conditions were positive for the risk of mental health dysfunction. In the domain assessing symptoms of severe depression, women with fourth-degree obstetric tear and genital tract fistula scored higher than women with pelvic organ prolapse. A significant risk of mental health dysfunction was identified in women with severe pelvic organ prolapse and chronic fourth-degree obstetric tear. These rates are similar to the high rates of mental health dysfunction in women with genital tract fistula. Identification and management of mental health dysfunction in women with these conditions should be a priority.

Unveiling relevant non-motor Parkinson's disease severity symptoms using a machine learning approach.

PubMed

Armañanzas, Rubén; Bielza, Concha; Chaudhuri, Kallol Ray; Martinez-Martin, Pablo; Larrañaga, Pedro

2013-07-01

Is it possible to predict the severity staging of a Parkinson's disease (PD) patient using scores of non-motor symptoms? This is the kickoff question for a machine learning approach to classify two widely known PD severity indexes using individual tests from a broad set of non-motor PD clinical scales only. The Hoehn & Yahr index and clinical impression of severity index are global measures of PD severity. They constitute the labels to be assigned in two supervised classification problems using only non-motor symptom tests as predictor variables. Such predictors come from a wide range of PD symptoms, such as cognitive impairment, psychiatric complications, autonomic dysfunction or sleep disturbance. The classification was coupled with a feature subset selection task using an advanced evolutionary algorithm, namely an estimation of distribution algorithm. Results show how five different classification paradigms using a wrapper feature selection scheme are capable of predicting each of the class variables with estimated accuracy in the range of 72-92%. In addition, classification into the main three severity categories (mild, moderate and severe) was split into dichotomic problems where binary classifiers perform better and select different subsets of non-motor symptoms. The number of jointly selected symptoms throughout the whole process was low, suggesting a link between the selected non-motor symptoms and the general severity of the disease. Quantitative results are discussed from a medical point of view, reflecting a clear translation to the clinical manifestations of PD. Moreover, results include a brief panel of non-motor symptoms that could help clinical practitioners to identify patients who are at different stages of the disease from a limited set of symptoms, such as hallucinations, fainting, inability to control body sphincters or believing in unlikely facts. Copyright © 2013 Elsevier B.V. All rights reserved.

Prevalence and risk factors for depression and anxiety in Chinese patients with Parkinson disease.

PubMed

Cui, Shi-Shuang; Du, Juan-Juan; Fu, Rao; Lin, Yi-Qi; Huang, Pei; He, Ya-Chao; Gao, Chao; Wang, Hua-Long; Chen, Sheng-Di

2017-11-22

Anxiety and depression are common in Parkinson disease and both are important determinants of quality of life in patients. Several risk factors are identified but few research have investigated general and Parkinson's disease (PD)-specific factors comprehensively. The aim of this work was to explore PD-specific and -non-specific risk factors for PD with depression or anxiety. A cross-sectional survey was performed in 403 patients with PD. Multivariate logistic analysis was used to investigate the prevalence and risk factors for the depression and anxiety in PD. The data of patients included demographic information, medicine history, disease duration, age at onset (AAO), family history, anti-parkinsonism drug, modified Hoehn and Yahr staging (H-Y) stage, scales of motor and non-motor symptoms and substantia nigra (SN) echogenic areas. 403 PD patients were recruited in the study. Depression and anxiety were present in 11.17% and 25.81% respectively. Marital status, tumor, higher Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) II score, dyskinesia, higher Hamilton Anxiety Rating Scale (HARS) score and lower the Parkinson's disease sleep scale (PDSS) score were associated with depression in PD. female gender, higher rapid eye movement behavior disorder Questionnaire-Hong Kong (RBD-HK) score, higher Hamilton Deprssion Rating Scale (HAMD) score, higher the scale for outcomes in PD for autonomic symptoms (SCOPA-AUT)score and larger SN echogenic areas were associated with anxiety. Neither depression nor anxiety was related to any anti-parkinsonism drugs. The prevalence of depression and anxiety in the current PD patients was 11.17% and 25.81% respectively. Disease of tumor, currently having no partner, severer motor function, dyskinesia, poorer sleep quality and anxiety were risk factors for PD with depression. Female, depression, rapid eye movement behavior disorder (RBD), autonomic dysfunction and larger SN area were risk factors for PD with anxiety.

Cardiovascular Autonomic Neuropathy and Glucose Variability in Patients With Type 1 Diabetes: Is There an Association?

PubMed

Nyiraty, Szabolcs; Pesei, Fruzsina; Orosz, Andrea; Coluzzi, Sara; Vági, Orsolya Eszter; Lengyel, Csaba; Ábrahám, György; Frontoni, Simona; Kempler, Peter; Várkonyi, Tamás

2018-01-01

The oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy (AN) has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV. Twenty type 1 diabetic patients were involved (age: 39.5 ± 3.4 years, duration of diabetes: 17.5 ± 2.5 years; HbA1c: 8.1 ± 0.2%, mean ± SE). AN was assessed by the cardiovascular reflex tests. The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on six consecutive days. GV was characterized by calculation of four parameters. SD of interstitial glucose values correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ = 0.47, p  < 0.05; orthostasis-SD: ρ = 0.51, p  < 0.05). Mean absolute glucose (MAG) correlated with three parameters of AN (AN-score-MAG: ρ = 0.62, p  < 0.01; 30/15 ratio-MAG: ρ = -0.50, p  < 0.05; orthostasis-MAG: ρ = 0.59, p  < 0.01). The HbA1c also correlated with two parameters of GV (HbA1c-continuous overlapping net glycemic action: ρ = 0.56, p  < 0.05; HbA1c-MAG: ρ = 0.45, p  < 0.05). The frequency of hypoglycemia did not exhibit any correlation with measures of GV. Severity of glucose variability but not overall glucose load correlates with both parasympathetic and sympathetic dysfunctions in type 1 diabetes. Higher HbA1c is associated with more severe glucose variability. The observed correlation between increased glucose variability and the severity of AN necessitates the further exploration of this relationship.

Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

PubMed

Planté-Bordeneuve, V; Ferreira, A; Lalu, T; Zaros, C; Lacroix, C; Adams, D; Said, G

2007-08-14

Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

PubMed

Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome.

PubMed

Roma, Maria; Marden, Colleen L; De Wandele, Inge; Francomano, Clair A; Rowe, Peter C

2018-03-05

To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings. Copyright © 2018 Elsevier B.V. All rights reserved.

Spinal tuberculosis, natural history of disease, classifications and principles of management with historical perspective.

PubMed

Kumar, Kush

2016-08-01

To describe the natural history spinal tuberculosis, classifications and principles of management based upon the grading of the neurological deficit. Review of literature was conducted with the aim to provide the clinico-radiological correlation of the natural history of spinal tuberculosis in different stages. Management strategy is developed based upon the severity of the neurological deficit. A five stage natural history of spinal tuberculosis is described. Stage of neurological involvement is further divided into 4 grades, predominantly on the basis of progressively increasing motor deficits as negligible, mild, moderate and severe with sensory and autonomic dysfunctions. Suitable principles of management with role of rest, braces, chemotherapy and surgery are discussed. Neurological deficit grading based management is developed. Grade 1 and 2, conservative treatment, grade 3, gray zone and grade 4, operative treatment is emphasized. The five stages of natural history of tuberculosis of spine have been developed from the clinician's point of view. Management of tuberculosis of spine, in general, it is no different than management of soft tissue tuberculosis, in HIV negative or positive patients. Role of surgery is very limited. Management of tubercular paraplegia, based upon the grading of paraplegia is simple, logical, efficient and easy to understand and remember by any orthopedic surgeon.

The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

PubMed Central

Ohta, Takeshi; Masuyama, Taku; Yokoi, Norihide; Kakehashi, Akihiro; Shinohara, Masami

2013-01-01

The Spontaneously Diabetic Torii (SDT) rat is an inbred strain of Sprague-Dawley rat and recently is established as a nonobese model of type 2 diabetes (T2D). Male SDT rats show high plasma glucose levels (over 700 mg/dL) by 20 weeks. Male SDT rats show pancreatic islet histopathology, including hemorrhage in pancreatic islets and inflammatory cell infiltration with fibroblasts. Prior to the onset of diabetes, glucose intolerance with hypoinsulinemia is also observed. As a result of chronic severe hyperglycemia, the SDT rats develop profound complications. In eyes, retinopathy, cataract, and neovascular glaucoma are observed. Proliferative retinopathy, especially, resulting from retinal neovascular vessels is a unique characteristic of this model. In kidney, mesangial proliferation and nodular lesion are observed. Both peripheral neuropathy such as decreased nerve conduction velocity and thermal hypoalgesia and autonomic neuropathy such as diabetic diarrhea and voiding dysfunction have been reported. Osteoporosis is another complication characterized in SDT rat. Decreased bone density and low-turnover bone lesions are observed. Taking advantage of these features, SDT rat has been used for evaluating antidiabetic drugs and drugs/gene therapy for diabetic complications. In conclusion, the SDT rat is potentially a useful T2D model for studies on pathogenesis and treatment of diabetic complications in humans. PMID:23691526

Identifying and assessing the substance-exposed infant.

PubMed

Clark, Lisa; Rohan, Annie

2015-01-01

As the rate of opioid prescription grows, so does fetal exposure to opioids during pregnancy. With increasing fetal exposure to both prescription and nonprescription drugs, there has been a concurrent increase in identification of Neonatal Withdrawal Syndrome (NWS) and adaptation difficulties after birth. In addition, extended use of opioids, barbiturates, and benzodiazepines in neonatal intensive care has resulted in iatrogenic withdrawal syndromes. There is a lack of evidence to support the use of any one specific evaluation strategy to identify NWS. Clinicians caring for infants must use a multimethod approach to diagnosis, including interview and toxicology screening. Signs of NWS are widely variable, and reflect dysfunction in autonomic regulation, state control, and sensory and motor functioning. Several assessment tools have been developed for assessing severity of withdrawal in term neonates. These tools assist in determining need and duration of pharmacologic therapy and help in titration of these therapies. Considerable variability exists in the pharmacologic and nonpharmacologic approaches to affected babies across settings. An evidence-based protocol for identification, evaluation, and management of NWS should be in place in every nursery. This article provides an overview of identification and assessment considerations for providers who care for babies at risk for or who are experiencing alterations in state, behavior, and responses after prenatal or iatrogenic exposure to agents associated with the spectrum of withdrawal.

Mother and daughter with adolescent-onset severe frontal lobe dysfunction and epilepsy

PubMed Central

dos Passos, Giordani Rodrigues; Fernández, Alonso Cuadrado; Vasques, Adriana Machado; Martins, William Alves; Palmini, André

2016-01-01

ABSTRACT Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed. PMID:29213461

Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Zesiewicz, T A; Sullivan, K L; Arnulf, I; Chaudhuri, K R; Morgan, J C; Gronseth, G S; Miyasaki, J; Iverson, D J; Weiner, W J

2010-03-16

Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here. A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tiered level of evidence scheme and recommendations were based on the level of evidence. Sildenafil citrate (50 mg) may be considered to treat erectile dysfunction in patients with Parkinson disease (PD) (Level C). Macrogol (polyethylene glycol) may be considered to treat constipation in patients with PD (Level C). The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements, and should be considered to treat periodic limb movements of sleep in patients with PD (Level B). There is insufficient evidence to support or refute specific treatments for urinary incontinence, orthostatic hypotension, and anxiety (Level U). Future research should include concerted and interdisciplinary efforts toward finding treatments for nonmotor symptoms of PD.

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; De Wandele, Inge; O'Callaghan, Chris; Pocinki, Alan; Rowe, Peter

2017-03-01

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Standard operating procedures for neurophysiologic assessment of male sexual dysfunction.

PubMed

Giuliano, Francois; Rowland, David L

2013-05-01

Can neurophysiological testing in male patients with sexual dysfunction benefit the decision-making process? The answer remains unclear. To provide standard operating procedures for the neurophysiologic assessment of male sexual dysfunction. Medical literature was reviewed and combined with expert opinion of the authors. Bulbocavernosus reflex latency time, pudendal somatosensory evoked potentials, and sympathetic skin responses have been considered as potential candidates for the diagnosis and assessment of erectile dysfunction (ED). Currently, there is no consensus on a standardized methodology for these neurophysiological investigations in the overall assessment of ED. These procedures are unable to assess the integrity of the efferent parasympathetic proerectile penile innervation; accordingly, none of these assessment procedures is recommended for ED patients. Corpus cavernosum electromyography (CC-EMG) can detect abnormalities in cavernous smooth muscle although these alterations can be attributed both to damage to autonomic penile innervation and to degenerative processes of the cavernous smooth muscle. CC-EMG is still considered experimental. Evidence does not support that men with premature ejaculation (PE) are consistently characterized by penile hypersensitivity; accordingly, penile threshold determination is not recommended to in the diagnosis of PE. Neurophysiological investigation of other components of the penile sensory pathways in PE patients has not provided any definitive contribution to the diagnosis. No neurophysiological assessment procedures yield additional information that consistently aids in the assessment of PE and ED. © 2013 International Society for Sexual Medicine.

Operator Informational Needs for Multiple Autonomous Small Vehicles

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.; Fan, Henry; Cross, Charles D.; Hempley, Lucas E.; Cichella, Venanzio; Puig-Navarro, Javier; Mehdi, Syed Bilal

2015-01-01

With the anticipated explosion of small unmanned aerial vehicles, it is highly likely that operators will be controlling fleets of autonomous vehicles. To fulfill the promise of autonomy, vehicle operators will not be concerned with manual control of the vehicle; instead, they will deal with the overall mission. Furthermore, the one operator to many vehicles is becoming a constant meme with various industries including package delivery, search and rescue, and utility companies. In order for an operator to concurrently control several vehicles, his station must look and behave very differently than the current ground control station instantiations. Furthermore, the vehicle will have to be much more autonomous, especially during non-normal operations, in order to accommodate the knowledge deficit or the information overload of the operator in charge of several vehicles. The expected usage increase of small drones requires presenting the operational information generated by a fleet of heterogeneous autonomous agents to an operator. NASA Langley Research Center's Autonomy Incubator has brought together researchers in various disciplines including controls, trajectory planning, systems engineering, and human factors to develop an integrated system to study autonomy issues. The initial human factors effort is focusing on mission displays that would give an operator the overall status of all autonomous agents involved in the current mission. This paper will discuss the specifics of the mission displays for operators controlling several vehicles.

Cardiopulmonary functional capacity and the role of exercise in improving maximal oxygen consumption in women with PCOS.

PubMed

Lenarcik, Agnieszka; Bidzińska-Speichert, Bozena

2010-01-01

Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorder in premenopausal women and is frequently accompanied by the presence of cardiovascular risk factors. It has also been recognized that PCOS women are characterized by cardiopulmonary impairment. Reduced cardiopulmonary functional capacity and the autonomic dysfunction associated with abnormal heart rate recovery might be responsible for the increased cardiovascular risk in patients with PCOS. Exercise training has beneficial effects on cardiopulmonary functional capacity and reduces the risk of cardiovascular disease in PCOS women.

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

PubMed

Wehrwein, Erica A; Orer, Hakan S; Barman, Susan M

2016-06-13

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Relations between social-perceptual ability in multi- and unisensory contexts, autonomic reactivity, and social functioning in individuals with Williams syndrome

PubMed Central

Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Arnold, Andrew J.; Woo-VonHoogenstyn, Nicholas; Bellugi, Ursula

2015-01-01

Compromised social-perceptual ability has been proposed to contribute to social dysfunction in neurodevelopmental disorders. While such impairments have been identified in Williams syndrome (WS), little is known about emotion processing in auditory and multisensory contexts. Employing a multidimensional approach, individuals with WS and typical development (TD) were tested for emotion identification across fearful, happy, and angry multisensory and unisensory face and voice stimuli. Autonomic responses were monitored in response to unimodal emotion. The WS group was administered an inventory of social functioning. Behaviorally, individuals with WS relative to TD demonstrated impaired processing of unimodal vocalizations and emotionally incongruent audiovisual compounds, reflecting a generalized deficit in social-auditory processing in WS. The TD group outperformed their counterparts with WS in identifying negative (fearful and angry) emotion, with similar between-group performance with happy stimuli. Mirroring this pattern, electrodermal activity (EDA) responses to the emotional content of the stimuli indicated that whereas those with WS showed the highest arousal to happy, and lowest arousal to fearful stimuli, the TD participants demonstrated the contrasting pattern. In WS, more normal social functioning was related to higher autonomic arousal to facial expressions. Implications for underlying neural architecture and emotional functions are discussed. PMID:26002754

Genetic contributions of the serotonin transporter to social learning of fear and economic decision making.

PubMed

Crişan, Liviu G; Pana, Simona; Vulturar, Romana; Heilman, Renata M; Szekely, Raluca; Druğa, Bogdan; Dragoş, Nicolae; Miu, Andrei C

2009-12-01

Serotonin (5-HT) modulates emotional and cognitive functions such as fear conditioning (FC) and decision making. This study investigated the effects of a functional polymorphism in the regulatory region (5-HTTLPR) of the human 5-HT transporter (5-HTT) gene on observational FC, risk taking and susceptibility to framing in decision making under uncertainty, as well as multidimensional anxiety and autonomic control of the heart in healthy volunteers. The present results indicate that in comparison to the homozygotes for the long (l) version of 5-HTTLPR, the carriers of the short (s) version display enhanced observational FC, reduced financial risk taking and increased susceptibility to framing in economic decision making. We also found that s-carriers have increased trait anxiety due to threat in social evaluation, and ambiguous threat perception. In addition, s-carriers also show reduced autonomic control over the heart, and a pattern of reduced vagal tone and increased sympathetic activity in comparison to l-homozygotes. This is the first genetic study that identifies the association of a functional polymorphism in a key neurotransmitter-related gene with complex social-emotional and cognitive processes. The present set of results suggests an endophenotype of anxiety disorders, characterized by enhanced social learning of fear, impaired decision making and dysfunctional autonomic activity.

Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE.

PubMed

Yuan, Junhui; Higuchi, Yujiro; Nagado, Tatsui; Nozuma, Satoshi; Nakamura, Tomonori; Matsuura, Eiji; Hashiguchi, Akihiro; Sakiyama, Yusuke; Yoshimura, Akiko; Takashima, Hiroshi

2013-03-01

DNMT1, encoding DNA methyltransferase 1 (Dnmt1), is a critical enzyme which is mainly responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy (HSAN) type IE with mutations in exon 20, and autosomal dominant cerebellar ataxia, deafness, and narcolepsy caused by mutations in exon 21. We report a sporadic case in a Japanese patient with loss of pain and vibration sense, chronic osteomyelitis, autonomic system dysfunctions, hearing loss, and mild dementia, but without definite cerebellar ataxia. Electrophysiological studies revealed absent sensory nerve action potential with nearly normal motor nerve conduction studies. Brain magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy. Using a next-generation sequencing system, 16 candidate genes were analyzed and a novel missense mutation, c.1706A>G (p.His569Arg), was identified in exon 21 of DNMT1. Our findings suggest that mutation in exon 21 of DNMT1 may also produce a HSAN phenotype. Because all reported mutations of DNMT1 are concentrated in exons 20 and 21, which encode the replication focus targeting sequence (RFTS) domain of Dnmt1, the RFTS domain could be a mutation hot spot. © 2013 Peripheral Nerve Society.

Reversible sympathetic vasomotor dysfunction in POTS patients.

PubMed

Freitas, J; Santos, R; Azevedo, E; Costa, O; Carvalho, M; de Freitas, A F

2000-11-01

Orthostatic intolerance refers to the development upon assuming an upright posture of disabling symptoms, which are partly relieved by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations due to excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurological and psychiatric evaluation, which usually fails to identify a specific abnormality. We investigated the autonomic and hemodynamic profile of POTS patients and the efficacy of bisoprolol and or fludrocortisone. We evaluated eleven female patients with POTS before and after medical treatment with a cardio-selective beta blocker (bisoprolol) and/or fludrocortisone, and eleven age-matched controls. Variability of heart rate and systolic blood pressure was assessed by Fast Fourier Transform, and spontaneous baroreceptor gain by temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. All patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol and/or fludrocortisone. These results need further confirmation in a controlled double-blind study. Proper medical treatment dramatically improves the clinical and autonomic/hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is due to a hyperadrenergic activation and/or hypovolemia during orthostasis.

Genetic contributions of the serotonin transporter to social learning of fear and economic decision making

PubMed Central

Crişan, Liviu G.; Pană, Simona; Vulturar, Romana; Heilman, Renata M.; Szekely, Raluca; Drugă, Bogdan; Dragoş, Nicolae

2009-01-01

Serotonin (5-HT) modulates emotional and cognitive functions such as fear conditioning (FC) and decision making. This study investigated the effects of a functional polymorphism in the regulatory region (5-HTTLPR) of the human 5-HT transporter (5-HTT) gene on observational FC, risk taking and susceptibility to framing in decision making under uncertainty, as well as multidimensional anxiety and autonomic control of the heart in healthy volunteers. The present results indicate that in comparison to the homozygotes for the long (l) version of 5-HTTLPR, the carriers of the short (s) version display enhanced observational FC, reduced financial risk taking and increased susceptibility to framing in economic decision making. We also found that s-carriers have increased trait anxiety due to threat in social evaluation, and ambiguous threat perception. In addition, s-carriers also show reduced autonomic control over the heart, and a pattern of reduced vagal tone and increased sympathetic activity in comparison to l-homozygotes. This is the first genetic study that identifies the association of a functional polymorphism in a key neurotransmitter-related gene with complex social–emotional and cognitive processes. The present set of results suggests an endophenotype of anxiety disorders, characterized by enhanced social learning of fear, impaired decision making and dysfunctional autonomic activity. PMID:19535614

Non-Motor Symptoms of Parkinson's Disease and Their Impact on Quality of Life in a Cohort of Moroccan Patients.

PubMed

Tibar, Houyam; El Bayad, Khalil; Bouhouche, Ahmed; Ait Ben Haddou, El Hachmia; Benomar, Ali; Yahyaoui, Mohamed; Benazzouz, Abdelhamid; Regragui, Wafa

2018-01-01

Non-motor symptoms (NMSs) are a real burden in Parkinson's disease (PD). They may appear in early pre-symptomatic stage as well as throughout the disease course. However, their relationship with the deterioration of the patient's quality of life (QoL) is still under debate. This study aimed to investigate the prevalence of NMSs and their impact on the QoL in a cohort of Moroccan patients. We carried out a cross-transactional study, where a total of 117 patients were submitted to a structured clinical interview and examination investigating motor and NMSs based on common and conventional scales. Motor symptoms were assessed by the UPDRS I-VI during ON condition. The NMSs were evaluated with common scales and their relationship with the QoL was investigated. The mean patient's age was 60.77 ± 11.36 years old, and the median disease duration was 6 years [2.5-9.5]. Motor's phenotype subtypes were the mixed form in 40.2% of patients, akinetic-rigid in 20.5% and a tremor-dominant form in 39.3%. The median Hoehn and Yahr staging was 2 [1-2.5]. Regarding NMSs, the most common were urinary dysfunctions (82.6%), sleep (80.6%), and gastrointestinal (80%) disorders. Other autonomic dysfunctions were also frequent: thermoregulatory dysfunctions 58.6%, cardiovascular troubles 50.9%, and sexual dysfunctions 47.9%. Depression was present in 47.9% and fatigue symptoms in 23.1%. The median score of SCOPA-AUT was 14 [7.75-21.80]. The median PD questionnaire 39-score index (PDQ39-SI) was 23.22% and the most affected dimension was "mobility." Univariate and multivariate analyses showed that the SCOPA-AUT score impacted the QoL ( p  = 0.001), especially the gastrointestinal ( p  = 0.007), and cardiovascular ( p  = 0.049) dimensions. Our data show that all patients have presented at least one NMS. Autonomic and sleep disorders were the most frequent, and in contrast to other studies, digestive and cardiovascular disorders were rather the factors influencing negatively the QoL of patients. Understanding the pathophysiology of these NMSs should be placed at the forefront in order to develop new therapeutic approaches by improving the QoL of PD patients.

Bilirubin-Induced Neurological Dysfunction: A Clinico-Radiological-Neurophysiological Correlation in 30 Consecutive Children.

PubMed

van Toorn, Ronald; Brink, Philip; Smith, Johan; Ackermann, Christelle; Solomons, Regan

2016-12-01

The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 consecutive children with bilirubin-induced neurological dysfunction seen over a period of 5 years. Thirty children exposed to acute neonatal bilirubin encephalopathy were included in the study. The mean peak total serum bilirubin level was 625 μmol/L (range 480-900 μmol/L). Acoustic brainstem responses were abnormal in 73% (n = 22). Pallidal hyperintensity was observed on magnetic resonance imaging in 20 children. Peak total serum bilirubin levels correlated with motor severity (P = .03). Children with severe motor impairment were likely to manifest severe auditory neuropathy (P < .01). We found that in a resource-constrained setting, classical kernicterus was the most common bilirubin-induced neurological dysfunction subtype, and the majority of children had abnormal acoustic brainstem responses and magnetic resonance imaging. © The Author(s) 2016.

Autonomous Relative Navigation for Formation-Flying Satellites Using GPS

NASA Technical Reports Server (NTRS)

Gramling, Cheryl; Carpenter, J. Russell; Long, Anne; Kelbel, David; Lee, Taesul

2000-01-01

The Goddard Space Flight Center is currently developing advanced spacecraft systems to provide autonomous navigation and control of formation flyers. This paper discusses autonomous relative navigation performance for a formation of four eccentric, medium-altitude Earth-orbiting satellites using Global Positioning System (GPS) Standard Positioning Service (SPS) and "GPS-like " intersatellite measurements. The performance of several candidate relative navigation approaches is evaluated. These analyses indicate that an autonomous relative navigation position accuracy of 1meter root-mean-square can be achieved by differencing high-accuracy filtered solutions if only measurements from common GPS space vehicles are used in the independently estimated solutions.

Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

PubMed

Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

2017-09-07

Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

PubMed Central

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-01-01

Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

PubMed

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-03-01

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

The hypertension of autonomic failure and its treatment

NASA Technical Reports Server (NTRS)

Shannon, J.; Jordan, J.; Costa, F.; Robertson, R. M.; Biaggioni, I.

1997-01-01

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Sexual Dysfunction and Sexual Behaviors in a Sample of Brazilian Male Substance Misusers.

PubMed

Diehl, Alessandra; Pillon, Sandra Cristina; Dos Santos, Manoel Antônio; Rassool, G Hussein; Laranjeira, Ronaldo

2016-09-01

The aim of this study was to evaluate the potential relationship between self-reported sexual dysfunction, sexual behavior, and severity of addiction of drug users. A cross-sectional design study was conducted at an inpatient addiction treatment unit in Sao Paulo, Brazil, with a sample of 508 male drug users. Sociodemographic data, sexual behavior, and severity of dependence were evaluated.The prevalence of sexual dysfunction was 37.2% and premature ejaculation was 63.8%. Men with sexual dysfunction presented from moderate to severe level of alcohol, tobacco, and other drugs of dependence. The findings from this study are particularly relevant identifying those sociodemographic factors, severity of drug use, and sexual behavior are related to men who experience sexual dysfunction. Health promotion and motivational interventions on sexual health targeted to male drug users can contribute in reducing these at-risk behaviors. More interdisciplinary research is desirable in future in considering men's sexual health. © The Author(s) 2015.

The diagnostic value of single-photon emission computed tomography/computed tomography for severe sacroiliac joint dysfunction.

PubMed

Tofuku, Katsuhiro; Koga, Hiroaki; Komiya, Setsuro

2015-04-01

We aimed to evaluate the value of single-photon emission computed tomography (SPECT)/computed tomography (CT) for the diagnosis of sacroiliac joint (SIJ) dysfunction. SPECT/CT was performed in 32 patients with severe SIJ dysfunction, who did not respond to 1-year conservative treatment and had a score of >4 points on a 10-cm visual analog scale. We investigated the relationship between the presence of severe SIJ dysfunction and tracer accumulation, as confirmed by SPECT/CT. In cases of bilateral SIJ dysfunction, we also compared the intensity of tracer accumulation on each side. Moreover, we examined the relationship between the intensity of tracer accumulation and the different treatments the patients subsequently received. All 32 patients with severe SIJ dysfunction had tracer accumulation with a standardized uptake value (SUV) of >2.2 (mean SUV 4.7). In the 19 patients with lateralized symptom intensity, mean SUVs of the dominant side were significantly higher than those of the nondominant side. In 10 patients with no lateralization, the difference in the SUVs between sides was <0.6. Patients exhibiting higher levels of tracer accumulation required more advanced treatment. Patients with higher levels of tracer accumulation had greater symptom severity and also required more advanced treatment. Thus, we believe that SPECT/CT may be a suitable supplementary diagnostic modality for SIJ dysfunction as well as a useful technique for predicting the prognosis of this condition.