Autonomic Impairment Research Articles

Cardiac autonomic modulation impairments in advanced breast cancer patients.

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 (30-69years 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.

A scoping review on health economics in neurosurgery for acute spine trauma.

OBJECTIVE Acute spine trauma (AST) has a relatively low incidence, but it often results in substantial individual impairments and societal economic burden resulting from the associated disability. Given the key role of neurosurgeons in the decision-making regarding operative management of individuals with AST, the authors performed a systematic search with scoping synthesis of relevant literature to review current knowledge regarding the economic burden of AST. METHODS This systematic review with scoping synthesis included original articles reporting cost-effectiveness, cost-utility, cost-benefit, cost-minimization, cost-comparison, and economic analyses related to surgical management of AST, whereby AST is defined as trauma to the spine that may result in spinal cord injury with motor, sensory, and/or autonomic impairment. The initial literature search was carried out using MEDLINE, EMBASE, CINAHL, CCTR, and PubMed. All original articles captured in the literature search and published from 1946 to September 27, 2017, were included. Search terms used were the following: (cost analysis, cost effectiveness, cost benefit, economic evaluation or economic impact) AND (spine or spinal cord) AND (surgery or surgical). RESULTS The literature search captured 5770 titles, of which 11 original studies met the inclusion/exclusion criteria. These 11 studies included 4 cost-utility analyses, 5 cost analyses that compared the cost of intervention with a comparator, and 2 studies examining direct costs without a comparator. There are a few potentially cost-saving strategies in the neurosurgical management of individuals with AST, including 1) early surgical spinal cord decompression for acute traumatic cervical spinal cord injury (or traumatic thoracolumbar fractures, traumatic cervical fractures); 2) surgical treatment of the elderly with type-II odontoid fractures, which is more costly but more effective than the nonoperative approach among individuals with age at AST between 65 and 84 years; 3) surgical treatment of traumatic thoracolumbar spine fractures, which is implicated in greater direct costs but lower general-practitioner visit costs, private expenditures, and absenteeism costs than nonsurgical management; and 4) removal of pedicle screws 1-2 years after posterior instrumented fusion for individuals with thoracolumbar burst fractures, which is more cost-effective than retaining the pedicle screws. CONCLUSIONS This scoping synthesis underscores a number of potentially cost-saving opportunities for neurosurgeons when managing patients with AST. There are significant knowledge gaps regarding the potential economic impact of therapeutic choices for AST that are commonly used by neurosurgeons.

BS05. Orthostatic hypotension and syncope in patients with ehlers-danlos syndrome

Introduction Postural tachycardia Syndrome (POTS) is a form of chronic orthostatic intolerance where the hallmark physiological trait is an excessive increase in heart rate upon standing. POTS is a final common pathway for a number of overlapping conditions, including lower body autonomic neuropathy, elevated sympathetic tone, mast cell activation, deconditioning, the presence of certain antibodies and hypovolemia. It also has similarities to chronic fatigue syndrome, Ehlers-Danlos Syndrome (EDS), vasovagal syncope and inappropriate sinus tachycardia. EDS is an heterogeneous disorder associated with inherited abnormalities of collagen structure. Patients develop hyper-extensibility, joint hypermobility and fragile connective tissue. Patients with EDS type III frequently have symptoms of autonomic dysregulation such as palpitations, lightheadedness, chest pain, presyncope and syncope that are also common in patients with POTS. Connective tissue abnormalities in EDS could lead to vascular laxity, predipose patients to orthostatic blood pooling in the lower extremities and orthostatic intolerance. These patients might have a peripheral neuropahty that could contribute to autonomic impairment. Methods Clinical records of patients diagnosed with Ehlers Danlos treated at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were reviewed retrospectively during a 10 year period (1987–2017). Results 29 patients were found to have a diagnosis of EDS. The female-to-male ratio was 3:1, while the mean age was 29. One patient died due to a ruptured aortic aneurysm. 9 (34.6%) patients had a history of presyncope, 14 patients (53%) had low blood pressure and 12 (46.15%) patients had heart rate values above 80 beats per minute. Mean systolic blood pressure was 107.2 ± 16, diastolic blood pressure 67.3 mmHg ± 10.8 with a mean heart rate of 80.1 ± 11.8. The most common Ehlers Danlos phenotype found was type III, which ocurred in 5 patients (40%). Type IV was found in 5 patients (26%), 3 patients (20%) presented with type VI and only two patients with type VII and type IX, respectively. We could not have the type of 14 patients. Conclusion Although is known that patients with the EDS may present with syncope or presyncopal episodes it is not known the percentage of patients who have dysautonomic cardiovascular symptoms and signs. We found that 53% of the patients have orthostatic intolerance, 34% had syncopal episodes and 46% could be diagnosed with POTS. One patient died due to a thoracic aortic aneurysm.

1021 Cognitive, Motor, and Autonomic Function Impairments in Idiopathic REM Sleep Behavior Disorder

1021 Cognitive, Motor, and Autonomic Function Impairments in Idiopathic REM Sleep Behavior Disorder

Serial holter recordings in non-cardiac surgery patients reveal postoperative autonomic impairment within 48 hours

Serial holter recordings in non-cardiac surgery patients reveal postoperative autonomic impairment within 48 hours

Characterizing the spectrum of autonomic impairment in neurologic disorders with calcium channel antibodies (P2.114)

Characterizing the spectrum of autonomic impairment in neurologic disorders with calcium channel antibodies (P2.114)

Cardiac Autonomic Control Impairment in Infants with Transient Hypertonia and Psychomotor Retardation

Transient hypertonia (TH) in early life is characterized by an increased muscular tone, postural restriction and decreased movement, all resulting in psychomotor retardation. Abnormalities of tone are an integral component of many transient or chronic motor disorders of childhood. Alterations in the concentration of several metabolites during changes in muscular tone may occur in infants with TH. Importantly, these metabolites have been shown to regulate cardiovascular function through the activation of the metaboreflex then regulating the activity of central sympathetic neurons that ultimately lead to cardiac adjustments through the modulation of autonomic function. Accordingly, we aimed to determine if TH infants showed alterations in cardiac autonomic control. Thirty subjects aged 0–24 months were recruited and allocated into 2 different groups: control (n=15), TH group (n=15) according to their neurological examination. Non-invasive measurements of cardiac autonomic function were assessed by linear and nonlinear analysis of heart rate variability (HRV). Compared to control healthy infants, TH group displayed higher resting heart rate values (129.93 ± 43.47 bpm vs 143.40 ± 9.93 bpm, Control vs TH, respectively; p<0.05) and showed overt signs of autonomic imbalance. Indeed, TH group displayed a significant increase in the low to high frequency ratio of the HRV compared to control (4,41 ± 1,78 vs. 7,54 ± 3,93; Control vs TH, respectively; p<0.05). Importantly, HRV in TH group infants were characterized by a shift in the spectral components towards sympathetic predominance as evidenced by a significant increase in the low frequency spectral component of the HRV (80,31 ± 4,84 vs. 86,03 ± 6,17 n.u., Control vs. TH, respectively; p<0.05). Also, parasympathetic withdrawal was evident in TH infants compared to healthy control since a TH infants showed a marked reduction in the high frequency components of the HRV compared to the values obtained in healthy control subjects (20,06 ± 4,39 vs. 13,97 ± 6,17 n.u., Control vs Hypertonia, respectively; p<0.05). Together, our results showed for the first time that infants with TH display cardiac autonomic imbalance. Support or Funding Information Supported by Fondecyt 1140275 For recording of HR and position child and parent and/or caregiver during measurement This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract 23: Lower Heart Rate Variability Associated With Incident Coronary Heart Disease and Death in Post-Menopausal Women

Rationale: Lower heart rate variability (HRV) has been associated with increased all-cause mortality and adverse cardiovascular events including sudden death. The role of HRV in post-menopausal women is understudied. Therefore, we tested the hypothesis of a significant association between HRV and incident coronary heart disease (CHD) and CHD death in post-menopausal women. Methods: This is an analysis of prospective data collected during the Women’s Health Initiative (WHI) clinical trials. A total of 57,061 post-menopausal women were included. HRV was quantified using two variables; standard deviation of all normal-to-normal RR intervals (SDNN, milliseconds), and the root mean square of successive differences in normal-to-normal RR intervals (RMSSD, milliseconds). We used Cox proportional hazards models to test the association between HRV and incident CHD, hard CHD (including myocardial infarction and fatal CHD), and total CHD death. We controlled for age, race, alcohol use, physical activity, depression, BMI, smoking, diabetes, hypertension, lipid disorders, and family history of CHD. Results: The results are as highlighted for incident and hard CHD in table 1 and for CHD death in table 2. There were statistically significant associations between lower HRV (as a continuous variable and as quartiles) and higher levels of incident CHD. Conclusion: In post-menopausal women, lower HRV was associated with a modestly higher, but statistically significant, risk for incident cardiovascular events, including fatal and non-fatal myocardial infarction. Factors associated with lower HRV and cardiac autonomic impairment may be candidates for reducing CHD risk, such as better glycemic control and improved physical activity.

Tonic peripheral chemoreflex activation contributes to cardiac autonomic modulation at rest and impairs cardiac baroreflex sensitivity during orthostatic challenge in patients with pulmonary arterial hypertension

Patients with pulmonary arterial hypertension (PAH) often experience orthostatic hypotension, and this may be mediated, to some extent, by impaired baroreflex sensitivity (BRS). The impairment in BRS is possibly caused by multiple factors. Of note, however, accumulating evidence has supported that tonic peripheral chemoreflex activation plays a key role for autonomic impairment in diseases like systemic hypertension and heart failure, due to, in part, alterations that are also commonly found in PAH (e.g., inflammation and oxidative stress). Thus we sought to test two hypotheses: 1) patients with PAH present impaired BRS during an orthostatic challenge; 2) the peripheral chemoreflex is sensitized in patients with PAH and contributes to cardiac autonomic modulation and BRS at rest and BRS during an orthostatic challenge. Twenty non‐hypoxemic patients with PAH and 10 healthy controls (CON) were assessed. Peripheral chemosensitivity was measured via the ventilatory response to transient inhalation of pure nitrogen. Beat‐by‐beat heart rate (ECG) and arterial pressure (finger photoplethismography) were measured at seated rest and during a repeated sit‐to‐stand maneuver (six consecutive repetitions of 10‐s sit and 10‐s stand), while participants randomly inhaled 100% of O2 to inhibit the peripheral chemoreflex tonic activity (i.e., hyperoxia), and 21% of O2 as control (i.e., normoxia). Isocapnia was maintained via a rebreathing system. Cardiac autonomic modulation was quantified via heart rate variability (HRV) indexes, which were calculated in time and frequency domains. The CBRS was calculated at rest via sequence and alpha index methods, and during a sit‐to‐stand maneuver via sequence method. The PAH group showed significantly higher peripheral chemosensitivity (PAH: 0.32 ± 0.04 vs CON: 0.18 ± 0.02 L/%SpO2, P &lt; 0.05) and significantly lower CBRS during the sit‐to‐stand maneuver, compared to the CON group. Peripheral chemoreflex inhibition via hyperoxia similarly increased HRV and CBRS in both groups at rest. In addition, hyperoxia significantly increased BRS during the sit‐to‐stand maneuver only in the PAH group, and then, the BRS was normalized (i.e., attained the CON group level). In summary, this study provides novel evidence that patients with PAH present low CBRS during an orthostatic challenge. Furthermore, data supports that the peripheral chemoreflex is sensitized and tonically contributes to cardiac autonomic modulation in patients with PAH at rest, and most notably, to impaired cBRS during an orthostatic challenge.Support or Funding InformationThe study was supported by São Paulo Research Foundation, FAPESP (2015/221982; 2017/077713)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Physical Exercise For Parkinson's Disease: Clinical And Experimental Evidence.

Background:National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated.Objective: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD.Methods:This study is a critical review of the literature.Results:The progressive death of dopaminergic neurons in the substantia nigra is described as one of the main physiological mechanisms manifested before PD, directly interfering with motor behavior. However, PD is not only related to motor symptoms, but also to cognitive, autonomic, and mood impairments. Such effects may be attenuated by pharmacological influence, but also evidence suggests that the implementation of regular physical exercise programs may exhibit potential benefits over PD. The synthesis and expression of monoaminergic neurotransmitters can act positively on motor disorders, as well as directly or indirectly influence the neuronal plasticity of the brain, restoring neuronal pathways previously affected.Conclusion:Physical exercise contributes effectively to the treatment of PD, and can play a preventive and maintenance role of physical fitness and mental health.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.

Cardiac Autonomic Function and Reactivity Tests in Physically Active Subjects with Moderately Severe COPD

ABSTRACTPatients with chronic obstructive pulmonary disease (COPD) show impairments in the autonomic nervous systems (ANS) function, which is responsible for cardiac autonomic regulation. This study assessed the autonomic function and cardio-vagal reactivity in conveniently sampled subjects with COPD participating in a pulmonary rehabilitation (PR) program. Twenty-six subjects with COPD and 22 age and gender matched control subjects were evaluated. R-R intervals were collected at rest in supine position. Thereafter, resting autonomic function parameters comprising linear and nonlinear analyses of heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated. Autonomic reactivity tests comprising deep breathing (DB), Valsalva maneuver (VM), and head up tilt (HUT) were also performed. The results of this study indicated that resting autonomic function variables were generally reduced in COPD compared to controls. However, this difference was only statistically significant for a few HRV parameters: mean RR intervals, low frequency (LF), standard deviation of dispersion of points perpendicular to the line-of-identity (SD1), and approximate entropy (ApEn) (p < 0.05). The results also indicated that all cardio-vagal indices following the autonomic reactivity tests were comparable between COPD and controls (p > 0.05). It was concluded that subtle autonomic impairments exists in physically active COPD patients, and these autonomic function deficits were mainly recognized by resting HRV indices and not autonomic reactivity tests.

Assessment of cardiac autonomic functions by heart rate variability in patients with restless leg syndrome.

The aim of the present study was to investigate cardiac autonomic effects in restless leg syndrome (RLS) using heart rate variability (HRV). A total of 35 patients with RLS and 35 healthy individuals were enrolled in the study. The severity of RLS symptoms was assessed using the International Restless Legs Syndrome Study Group rating scale (IRLS). The correlation between the severity of RLS symptoms and HRV parameters measured on an electrocardiogram was analyzed. There were no statistically significant differences between the 2 groups with respect to age, gender, or body mass index. The mean heart rate was 85±7.1 bpm in the RLS group compared with 79.6±5.5 bpm in the control group (p=0.001). The standard deviation (SD) of all normal to normal (NN) intervals (SDNN), the mean of the deviation of 5-minute NN intervals over the entire recording (SDNN index), and the SD of the average NN intervals calculated over a 5-minute period of the entire recording (SDANN) were significantly lower in the RLS group compared with the control group (p<0.05 for all). There were no statistically significant differences between the 2 groups in the square root of the mean squared differences of successive NN intervals (RMSSD) and the proportion of adjacent RR intervals differing by >50 milliseconds in the 24-hour recording (pNN50) values (p=0.119 and p=0.07, respectively). In patients with RLS, the low frequency (LF) power and LF/high frequency (HF) ratio were significantly higher than those in the control group (2248.6±245.6 vs 712.1±346.3, 10.7±3.7 vs 2.9±1.8; p<0.0001 and p<0.0001, respectively). Compared with the control group, the RLS group had lower values for HF power, but the difference was not statistically significant (p=0.07). The severity of RLS symptoms was negatively correlated with the SDNN, SDANN index, and pNN50 (r=-0.453 and p=0.009, r=-0.340 and p=0.046, r=-0.446 and p=0.007, respectively), and positively correlated with LF power (r=0.681 and p<0.0001). The study data demonstrated that cardiac autonomic impairment is associated with RLS.

Gullain Barre Syndrome in an 18 month old child: A case report

Gullian Barre Syndrome is a post infectious poly neuropathy mainly involving motor, but sometimes also sensory and autonomic nerves. Recent immunization with influenza, oral polio and rabies are included in etiology. Pure motor axonal type has the highest incidence in paediatric population. There is flaccid ascending paralysis with areflexia. Autonomic and cranial nerve impairment are also noted. We are presenting a case of 18 months old female child, partially vaccinated, weighing 9kg, who presented with complains of generalized for two days and inability to walk for one day. Child had upper respiratory tract infection two weeks back for which she took oral antibiotics. Milestones were appropriate for age. On examination GCS was 7/15, cranial nerves intact , hypotonia with areflexia and decrease power in all four limbs. Rest of the systemic examination was unremarkable. Laboratory investigations showed leuckocytosis with normal electrolytes and renal functions. However CSF showed pleocytosis with normal glucose and WBC count. Stool culture for polio virus was sent and found to be negative. Our provisional diagnosis is acute flaccid paralysis which could be due to poliomyelitis, gullain barre syndrome and botulinism. History, examination and CSF D/R was suggestive of gullain barre syndrome, so final diagnosis was made. Child was intubated in PICU immediately after shift from emergency due to labored breathing and low GCS. Child was on ventilator support for two days. Intravenous immunoglobulin were arranged and given but unfortunately child expired on second day of admission. Gullain barre syndrome is one of the important cause of acute flaccid paralysis and it is associated with highest mortality incases with rapid onset of limb weakness and mechanical ventilation.

Sleep and autonomic impairment in Ehlers-Danlos syndrome: a case series

Sleep and autonomic impairment in Ehlers-Danlos syndrome: a case series

Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease.

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 20years, 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.

A Systematic Review of Investigations into Functional Brain Connectivity Following Spinal Cord Injury.

Background: Complete or incomplete spinal cord injury (SCI) results in varying degree of motor, sensory and autonomic impairment. Long-lasting, often irreversible disability results from disconnection of efferent and afferent pathways. How does this disconnection affect brain function is not so clear. Changes in brain organization and structure have been associated with SCI and have been extensively studied and reviewed. Yet, our knowledge regarding brain connectivity changes following SCI is overall lacking.Methods: In this study we conduct a systematic review of articles regarding investigations of functional brain networks following SCI, searching on PubMed, Scopus and ScienceDirect according to PRISMA-P 2015 statement standards.Results: Changes in brain connectivity have been shown even during the early stages of the chronic condition and correlate with the degree of neurological impairment. Connectivity changes appear as dynamic post-injury procedures. Sensorimotor networks of patients and healthy individuals share similar patterns but new functional interactions have been identified as unique to SCI networks.Conclusions: Large-scale, multi-modal, longitudinal studies on SCI patients are needed to understand how brain network reorganization is established and progresses through the course of the condition. The expected insight holds clinical relevance in preventing maladaptive plasticity after SCI through individualized neurorehabilitation, as well as the design of connectivity-based brain-computer interfaces and assistive technologies for SCI patients.

A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin.

The FOLFOX family of chemotherapy regimens are hampered by the development of a painful neuropathy. Current clinical treatments are inadequate, and furthermore, the research of innovative drugs is strongly disadvantaged by the absence of a preclinical model based on the complete mixture of FOLFOX components. The aim of this study was to set up a rat model of FOLFOX-induced neuropathy in rats, validate its predictability by reference drugs, and evaluate the effectiveness of the new anti-neuropathic compound dimiracetam. Male Sprague-Dawley rats were treated intraperitoneally with the FOLFOX components (6mgkg-1 oxaliplatin, 50mgkg-1 5-FU, 90mgkg-1 leucovorin calcium salt) or oxaliplatin alone (6mgkg-1) on days 0, 7, 14, and 21, whereas a separate group received one more injection of FOLFOX on day 28. Pain behavioural measurements (paw pressure, cold plate, and electronic Von Frey tests) and motor coordination (Rota-rod test) were assessed before and after treatments. Behavioural, motor, neurological, and autonomic parameters (open field and Irwin tests) were evaluated. FOLFOX reduced the pain threshold in response to mechanical noxious and thermal (cold) non-noxious stimuli beginning from day 14 up to day 42 comparably to oxaliplatin alone. A fifth FOLFOX injection enhanced the severity but not the duration of painful alterations. Spontaneous activity, behavioural, autonomic, and neurological functions were also affected, whereas the motor coordination was not altered. On day 22, duloxetine (15mgkg-1, per os), morphine (10mgkg-1, subcutaneously), or pregabalin (20mgkg-1, per os), acutely administered, reduced the FOLFOX-dependent hypersensitivity. Repeated treatments with dimiracetam (150mgkg-1, per os, twice daily, from day 22) significantly protected rats from FOLFOX-induced alterations of pain threshold as well as from autonomic and neurological impairments taking effect after 7 days treatment. Pregabalin repeatedly administered (20mgkg-1, per os, twice daily, from day 22) was less effective in reducing mechanical hypersensitivity. A clinically consistent model of FOLFOX-induced neurotoxicity has been developed in rats. Dimiracetam fully reduced hypersensitivity and neurological alterations showing a relevant profile as anti-neuropathic resource.

Autonomic Dysfunction in Wilson's Disease: A Comprehensive Evaluation during a 3-Year Follow Up.

Objectives: Wilson's disease is reported to have autonomic dysfunction, but comprehensive evaluation of autonomic function is lacking. Additionally, little is known about the change of autonomic function of Wilson's disease during continuous therapy. We assumed that patients with Wilson's disease had both sympathetic and parasympathetic autonomic impairments, and the autonomic dysfunction might be stable across a 3-year follow-up after years of optimal treatment.Methods: Twenty-six patients with Wilson's disease and twenty-six healthy controls were recruited. Twenty patients in the Wilson's disease group were examined again after a 3-year follow-up. All the participants were evaluated by a questionnaire on dysautonomia symptoms, 24-h blood pressure and heart rate monitoring, and cardiovascular autonomic function examination in various conditions including at rest, deep breathing, Valsalva maneuver, isometric handgrip test and passive tilting. Baroreflex sensitivity and spectral analyses were performed via trigonometric regressive spectral analysis.Results: Patients with Wilson's disease showed autonomic dysfunction mainly in the following aspects: (1) the heart rate was higher than the controls. (2) Valsalva ratio was lower in patients with Wilson's disease compared with the controls. (3) Heart rate increase during isometric hand gripping was smaller in the Wilson's disease patients than the controls. (4) Baroreflex sensitivity was lower during nearly all the cardiovascular autonomic function examinations compared with healthy controls. When tested 3 years later, baroreflex sensitivity at rest decreased compared with baseline. (5) There were mild declines of resting DBP and low frequency component of heart rate variability during the follow-up examination compared with baseline. (6) Subgroup analysis showed that patients initially presenting with neurological symptoms had a higher night-time heart rate, lower expiration: inspiration RR interval ratio (E/I ratio), lower expiration: inspiration RR interval difference (E-I difference), less increase of heart rate and diastolic blood pressure during the handgrip test, and lower baroreflex sensitivity during deep breathing than the control group. (7) Correlation analysis showed that the severity of neurological symptoms was associated with E/I ratio, E-I difference, Valsalva ratio, heart rate change during the handgrip test, and baroreflex sensitivity during deep breathing.Conclusions: The present study reveals cardiovascular autonomic dysfunction involving both sympathetic and parasympathetic branches in Wilson's disease patients, which is especially significant in the patients with neurological onset. Autonomic function is generally stable undergoing optimal maintenance treatment in patients with Wilson's disease. Though there might be mild changes of specific parameters.

Prevalence of resting bradycardia, resting hypotension and orthostatic hypotension in chronic spinal cord injury patients

Background: Spinal cord injury (SCI) is a devastating event which usually leads to the impairment of autonomic nervous system and also causes many acute and chronic complications. There are very few clinical tests to assess the proper functioning of the autonomic nervous system. So, it is hypothesized to access the presence of resting bradycardia, resting hypotension and orthostatic hypotension and to use them as indirect indicators for the autonomic dysfunction in chronic spine cord injury (SCI) patients.Methods: The study was an analytic cross-sectional study, to assess the prevalence of resting bradycardia, resting hypotension and orthostatic hypotension in the spinal cord injury patients.Results: This study was conducted on 87 SCI patients, out of which 58 were paraplegics (21 having complete spinal cord injury, 37 with incomplete spinal cord injury) and 29 tetraplegics (13 with complete spinal cord injury, 16 with incomplete spinal cord injury). Orthostatic hypotension (67% vs 48.65%), resting hypotension (38.09% versus 29.7%) and resting bradycardia (33.33% versus 27.03%) were more amongst paraplegics patients with complete spinal cord injury as compared to paraplegics with incomplete spinal cord injury patients. All tetraplegic patients with complete spinal cord injury had resting bradycardia. Orthostatic hypotension, resting hypotension was found to be greater in tetraplegic patients with complete spinal cord injury.Conclusions: Complications due to autonomic impairment pose day to day difficulties in life of chronic SCI patients hampering their quality of life. So, the assessment of autonomic functions must be a part of clinical evaluation of individuals with SCI and efforts must be made to tackle these complications in the best possible way.