Autonomic Dysfunction Research Articles

Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study

BackgroundThe burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown. ObjectivesWe evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors. MethodsWe conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo2 < 80% predicted). ResultsSurvivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001). ConclusionsSurvivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.

Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: A pilot study

Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are debilitating post-viral conditions with many symptomatic overlaps, including exercise intolerance and autonomic dysfunction. Both conditions are growing in prevalence, and effective safe treatment strategies must be investigated. We hypothesized that inspiratory muscle training (IMT) could be used in PASC and mild to moderate ME/CFS to mitigate symptoms, improve exercise capacity, and improve autonomic function. We recruited healthy controls (n=12; 10 women), people with PASC (n=9; 8 women), and people with mild to moderate ME/CFS (n=12; 10 women) to complete 8 weeks of IMT. This project was registered as a clinical trial (NCT05196529) with clinicaltrials.gov. After completion of IMT, all groups experienced improvements in inspiratory muscle pressure (p<0.001), 6-minute walk distance (p=0.002), resting heart rate (p=0.037), heart rate variability (p<0.05), and symptoms related to sleep (p=0.009). In the ME/CFS group only, after completion of IMT, there were additional improvements with regard to vascular function (p=0.001), secretomotor function (p=0.023), the total weighted score (p=0.005) of the COMPASS 31 autonomic questionnaire, and symptoms related to pain (p=0.016). We found that after 8 weeks of IMT, people with PASC and/or ME/CFS could see some overall improvements in their autonomic function and symptomology.

“Assessment Of Cardiac Autonomic Dysfunction In Children With Cerebral Palsy Using Heart Rate Variability”

Background: Cardiac autonomic imbalance in children with CP might be due to primary brain insult, vary with different levels of Gross Motor Functional Classification System or may alter with multimodal therapies in various types of cerebral palsy (1,2) . It is important to understand and to create awareness that autonomic impairment in children with CP is in part due to sedentary lifestyle (3).HRV(Heart Rate Variability) in cerebral palsy is recognized as an important tool for monitoring cardiovascular health, in which autonomic imbalance is characterized by reduced HRV (i.e. regarded as increased cardiac sympathetic activity and decreased vagal modulation) (4,5) . Of the research that does exist, each study discusses only very few parameters of the autonomic nervous system, thus providing opportunities for further research and hence the need for the study. Materials and Methods: This is a cross-sectional case control study of 51 children with Cerebral Palsy (CP) and 51 normal children, conducted at District Early Intervention Centre (DEIC) in the Department of Paediatrics, Vani Vilas hospital. These 51 cases were assessed and classified based on their demographic features, etiology, type of CP, GMFCS scale and with the objectives of assessing the heart rate variability (HRV) in children with cerebral palsy and compare it with controls in both supine position and after a stress test, and also to correlate the obtained parameters with GMFCS level, type of CP using a systematically designed proforma. Results: Results of the study showed that of the children with CP studied, 62% were male children, and majority of were between 6-8 years of age (58%), and it was found that the most common etiology for CP in our study was due to perinatal asphyxia (43%), and 80% of the children had history of NICU admission. Of the 51 cerebral palsy children studied 72% were in GMFCS levels 3 and 4, regarding the topographical classification majority had spastic quadriplegia (58.8%) followed by spastic diplegia (15.7%). Study revealed that cerebral palsy children had significantly lower HRV, higher sympathetic activity, autonomic response deficit to stress test, and higher autonomic dysfunction when compared to normal children. Among cases, HRV was lowest with spastic quadriplegia and triplegic CP, in functional classification HRV was lowest among GMFCS 4 and 3. Conclusion: Cerebral palsy children had significantly higher sympathetic activity and less cardiac vagal modulation compared to normal children in supine position and there was existence of autonomic response deficit in cerebral palsy children after stress test, higher the motor impairment, higher was the sympathetic activity

Autonomic Dysfunction in Psychiatric Disorders

The autonomic nervous system and its dysfunction are associated with many diseases. For a healthy individual, it is essential that the sympathetic and parasympathetic systems are balanced and functioning at a high capacity. Psychiatric disorders often exhibit disruptions in the activity of the vagus nerve, which can lead to autonomic dysfunction. People with psychiatric disorders, including panic disorder, depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety disorders, and substance addiction, often show reduced heart rate variability. Heart rate variability is a reliable marker for assessing autonomic functions, and decreased heart rate variability in individuals with psychiatric disorders can lead to an increased risk of sudden cardiac death. Autonomic dysfunction is observed in psychiatric disorders, and it occurs during the course of the illness, not necessarily at its onset. Autonomic dysfunction accelerates the progression of the disease. Therefore, controlling autonomic functions is crucial. This can help reduce disease symptoms and decrease the morbidity and mortality caused by autonomic dysfunction."

Slow breathing exercise improves cardiac autonomic tone in hypothyroid patients: a frequency domain analysis of HRV

Background: Hypothyroidism is associated with autonomic dysfunction and oxidative stress. Slow breathing exercise (SBE), a yoga-based relaxation technique, improves cardiac autonomic nerve function by changing sympathetic or parasympathetic activity. Objective: To assess the effect of SBEon cardiac autonomic tone and in hypothyroid patients. Methods: This non randomized controlled trial was conducted on 50 newly diagnosed drug naive female hypothyroid patients (18-45 years of age)recruited from the outpatient department of the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University,(BSMMU), Shahbag, Dhaka. Twenty five apparently healthy female subjects formed control group. . Among the 50 hypothyroid patients, 25 were consecutively assigned with SBE for 90 days (Group SBE) and the remaining 25 patients were without SBE and followed up after 90 days (Group NSBE). Both groups of patients received treatment with thyroid hormone replacement during their follow up period. Control group did not perform SBE or any other exercise. Data were recorded at baseline(Day 0) and after 90 days in all the subjects. Based on data recording period SBE group was designated as SBE0(at day 0 or pre intervention)and SBE90(at day 90 or post intervention). Similarly, NSBE0(day 0) and NSBE90 (day 90) and control group was also designated as control0 (day 0) and control90 (day 90).Resting cardic autonomic tonic activity was assessed by frequency domain analysis of Heart Rate Variability(HRV). HRV data were recorded by a digital data acquisition device Power Lab, AD Instrument Australia. Data were expressed as mean±SD. For statistical analysis, ANOVA followed by post hoc Bonferroni test and paired sample “t” test were done. Results: At baseline i.e. at day 0 before follow up, diastolic blood pressure (DBP) (p&lt;0.05), low frequency in normalized unit (LF norm) (p&lt;0.001), low frequency/high frequency ratio (LF/HF) (p&lt;0.001) were significantly higher and total power (TP) (p&lt;0.001), low frequency power (LF power) (p&lt;0.01), high frequency power (HF power) (p&lt;0.001), high frequency power in normalized unit (HF norm) (p&lt;0.001) were significantly lower in hypothyroid patients (group SBE0and NSBE0 ) compared to healthy control (group control0). After 90 days of intervention with SBE, SBP, DBP, LF norm, LF/HF ratio decreased significantly and TP, HF power, HF norm increased significantly in group SBE90 compared to SBE0. Whereas, in group NSBE90, after 90 days of follow up, LF norm, LF/HF ratio decreased significantly and HF power, HF norm increased significantly compared to NSBE0. Again, after 90 days of follow up/SBEHF norm were significantly higher and LF norm, LF/HF ratio were significantly lower in SBE90 compared to NSBE90. In addition, significant difference was present in all these parameters between NSBE90 and control90. Also, after 90 days of SBELF norm, HF norm and LF/HF ratio was not significantly different from control. Conclusions: Based on these results, it can be concluded that autonomic dysfunction characterized by reduced vagal tone and sympathetic hyperactivity occurred in drug naïve hypothyroid patients. In addition, thyroid hormone replacement therapy improved autonomic dysfunction by increasing parasympathetic and decreasing sympathetic tonic activity. Moreover, SBE caused further improvement of autonomic dysfunction and could restore sympathovagal balance to its normal state in these patients. J Bangladesh Soc Physiol 2023;18(1): 9-18

Effect of slow breathing exercise on heart rate variability: A non linear analysis in female major depressive disorder patients

Background: Major depressive disorder (MDD) is a mental health problem, associated with cardiac autonomic dysfunction. Cardiac autonomic function (CANF) can be assessed by non linear analysis of heart rate variability (HRV), a simple non-invasive software based analytical method. Yoga based slow breathing exercise (SBE) has role to improve autonomic dysfunction in some disease condition. Objective: To observe the effect of SBE on non linear measures of HRV in newly diagnosed female MDD patients. Methods: The quasi-experimental study was conducted in 2023 on sixty (60) newly diagnosed female MDD patients of 20-40 years aged, collected from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University (BSMMU). Among them 30 were assigned with SBE and remaining 30 patients without SBE were followed up after 90 days. Both patient groups received conventional treatment during this period. Thirty apparently healthy female subjects with similar age &amp; BMI were included as control for comparison and they did not perform breathing exercise. Data were taken at baseline and after 90 days in all the subjects. CANF was assessed by analysing non linear (poincare plot) of HRV by using ECG based data acquisition device, Power lab 8/35. Data were expressed as mean±SD. For statistical analysis, ANOVA followed by post hoc Bonferroni test and paired sample “t” test were used. Results: At baseline pulse rate and BP were significantly lower in both group of MDD patients compared to control. The pre-intervention values of standard deviation of short term RR interval variability (SD1), standard deviation of long term RR interval variability (SD2) and ratio of short term and long term RR interval variability (SD1/SD2) were found significantly (p&lt; 0.001) lower in MDD patients compared to healthy control. Following 90 days of SBE, significant (p&lt; 0.001, p&lt; 0.05) rise of these poincare plot parameters was noted in MDD patients whereas no significant changes of these parameters were observed in patients without SBE after 90 days of follow-up. Moreover, the pulse BP almost reached control level though the non linear parameters were still below control level after 3 months of SBE.. Conclusion: Autonomic dysfunction occured in MDD patients SBE can improve cardiac autonomic dysfunction and sympathovagal balance in female MDD patients. J Bangladesh Soc Physiol 2023;18(2): 45-52

Enhancements in Parkinson's Disease Management: Leveraging Levodopa Optimization and Surgical Breakthroughs.

Parkinson's disease (PD) is a complex neurological condition caused due to inheritance, environment, and behavior among various other parameters. The onset, diagnosis, course of therapy, and future of PD are thoroughly examined in this comprehensive review. This review also insights into pathogenic mechanisms of reactive microgliosis, Lewy bodies, and their functions in the evolution of PD. It addresses interaction complexity with genetic mutations, especially in genes such as UCH-L1, parkin, and α-synuclein, which illuminates changes in the manner dopaminergic cells handle proteins and use proteases. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy. This raises the improved outcomes and life quality for those with PD. Potential treatments for severe PD include new surgical methods like Deep Brain Stimulation (DBS). Further, exploration of non-motor manifestations, such as cognitive impairment, autonomic dysfunction, and others, is covered in this review article. These symptoms have a significant impact on patients' quality of life. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy.

Effect of lemongrass (Cymbopogoncitratus) essential oil on cardiac autonomic function in female Generalized Anxiety Disorder:A poincaré analysis of heart rate variability

Background:Generalized anxiety disorder (GAD) is a worldwide, one of most prevalent mental disorder and associated with autonomic dysfunction. Poincaré plot of heart rate variability (HRV) is anonlinear method to assess cardiac autonomic nerve function (CANF).Lemongrass (Cymbopogoncitratus) essential oil (LEO) has been reported with anxiolytic effect and autonomic improvement in human. Objective: To assess the effect of LEO inhalation on CANF in female patients with GAD by analysis of poincaré plot of HRV.Method: This Quasi experimental study was conducted on 60 newly diagnosed female GAD patients with 20-40 years of age. Among them, 30 patients were treated with LEO inhalation for 15 min for once a week for one month (30days)along conventional treatment and 30 patients were without LEO inhalation and continued only conventional treatment for 30days.Thirty (30) apparently healthy subjects were control group.HRV data of all patients and control were recorded at baseline and after 30days of intervention or follow up respectively. HRV was recorded by a data acquisition device, Power Lab 8/35 and Poincaré plot analysis was done by lab chart software. For statistical analysis ANOVA followed by post-hoc test and paired sample ‘t’ test were done.Results: In this study, at baseline, the standard deviation of the short-term RR interval variability (minor axis of the cloud, SD1),the standard deviation of the long-term RR interval variability (major axis of the cloud, SD2) and SD1/SD2 were found significantly lower (p&lt;0.001) in all GAD patients compared to control group. After 30 days of intervention with LOE, significant increase of SD1(p&lt;0.001) and SD2, SD1/SD2 (p&lt;0.01) were found in GAD patients whereas no significant difference was found in patients without LEO after 30 days. Moreover, significantly higher values of SD1 and SD2 were observed in GAD patients after aroma therapy with LEO compared to GAD patients not under aroma therapy. Furthermore, LEO could restore the BP of the GAD to the control level. Conclusion: This study concluded that, aromatherapy with LEO inhalation may be effective to improve cardiac autonomic dysfunction in female GAD patients. J Bangladesh Soc Physiol 2023;18(1): 19-26

Pelvic autonomic dysfunction is common in patients with pure autonomic failure.

Pure autonomic failure (PAF) presents primarily as cardiovascular autonomic failure and may phenoconvert to other neurodegenerative disorders. However, the involvement of other autonomic functions has been poorly evaluated. This study aims to characterize genitourinary and bowel dysfunction and explore their relationship with cardiovascular autonomic dysfunction. Pure autonomic failure patients underwent cardiovascular autonomic testing and an assessment of pelvic autonomic dysfunction using urinary, sexual symptoms questionnaires and a bladder diary. Demographic, clinical features and related medical comorbidities were assessed. Twenty-five patients (10 males) with PAF were included (mean age 71 ± 8 years; disease duration 13 ± 8 years). 96% (24/25) reported lower urinary tract symptoms, of which overactive bladder symptoms were most commonly reported (n = 23; 92%; median overactive subscore 8, interquartile range [IQR] 3-11), followed by voiding difficulties (n = 19; 76%; median low stream subscore 2, IQR 1-3) using the Urinary Symptom Profile; however, only four (16%) required clean intermittent self-catheterization. Sexual dysfunction was common (n = 21; 84%) using the Arizona Sexual Experience Scale. Mild faecal incontinence and constipation were reported. 86% (19/22) had nocturnal polyuria (NP) and the median NP index was 47% (IQR 38%-51%; normal range <33%). 77% (10/13) had voiding dysfunction and 31% (4/13) had post-void residual urine >100 mL. There were no significant correlations between the need for catheterization and the degree of NP with age, disease duration and cardiovascular autonomic parameters (p > 0.05). Nocturnal polyuria, genitourinary and bowel symptoms are commonly seen in PAF. The pathophysiology of NP in PAF is most likely multifactorial and may occur independent of cardiovascular autonomic failure.

Association of cardiac autonomic nerve function with serum zinc, calcium and magnesium in female hypothyroid patients

Background: Hypothyroidism is related to impaired cardiac autonomic nerve activity with altered levels of serum Zinc (Zn), Calcium (Ca) ‍and Magnesium (Mg).Altered Serum Zn,Caand Mg levels are also associated with autonomic imbalance and may raise cardiovascular risk.Heart rate variability (HRV) is an important marker for assessing cardiac autonomic nerve function(CANF). Objectives: To evaluate the association of serum Zn, Cal and Mglevels withCANF in female hypothyroid patients. Methods: This analytical cross-sectional study was conducted on 40 female hypothyroid patients aged 18-45 years. Thirty apparently healthy women were control. Serum Zn, Ca and Mg levels were estimated by autoanalyzer and CANF was assessed by time domain analysis of HRV recorded by Power Lab 8/35 AD Instruments, Australia. Statistical analysis was done by Independent sample‘t’ test, One way ANOVA followed by post-hoc Bonferroni test and Pearson’s correlation coefficient test. Results: Among time domain parameters of HRV, standard deviation of the RR intervals (SDRR), coefficient variation of RR interval (CVRR), SD rate, standard deviation of the difference between successive RR intervals (SDSD), square root of mean squared differences of successive RR intervals (RMSSD), proportion of RR interval with duration &gt;50 ms (pRR50%) were significantly lower (p&lt;0.05) in all hypothyroid patients as compared to control. On correlation analysis, serum Zn, Ca and Mg were significantly positively correlated with SDSD(p&lt;0.01, p&lt;0.001,p&lt;0.01) RMSSD(p&lt;0.01, p&lt;0.001, p&lt;0.01), pRR50%(p&lt;0.01, p&lt;0.01, p&lt;0.05)and serum Ca was also positively correlated with SDRR(p&lt;0.05) in hypothyroid patients. Conclusion:Serum ZnCa and Mg were associated with cardiac autonomic dysfunction. in female hypothyroid patients. J Bangladesh Soc Physiol 2023;18(1): 27-34

Autonomic Dysfunction in Fibromyalgia Patients: Electrophysiological Evidence from a Cross-sectional Study in Kochi, India

Background: Over the decades, studies from various populations have found fibromyalgia and dysautonomia to be linked. However, recent evidence from Indian populations contradicts these findings. Methods: This cross-sectional study, conducted in a quaternary care centre in South India, recruited 30 women with fibromyalgia (2016 ACR criteria) and 30 age and sex-matched controls. We assessed all participants using Composite Autonomic Symptom Score (COMPASS-31) questionnaires, Sympathetic Skin Response (SSR) for sympathetic dysfunction and Heart Rate Variability battery of tests for parasympathetic dysfunction. Results: Median age of the women was 40 years. Fibromyalgia group reported severe levels of pain and disease impact on life. Fourteen participants (46.7%) with fibromyalgia tested positive for either sympathetic or parasympathetic dysfunction or both, while none of the control participants tested positive for either (odds ratio [OR] = 53.6, 95% confidence interval [CI] = 3–957, p = 0.0068). Conclusion: Dysautonomia is strongly associated with fibromyalgia syndrome. Further research is needed to determine causality.

Chronic lymphoproliferative disorder of natural killer cells-related neurolymphomatosis with severe autonomic dysfunction: a case report

BackgroundChronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms.Case presentationThe patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement.ConclusionsWe experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required.

Asymmetry in Atypical Parkinsonian Syndromes—A Review

Background/Objectives: Atypical parkinsonian syndromes (APSs) are a group of neurodegenerative disorders that differ from idiopathic Parkinson’s disease (IPD) in their clinical presentation, underlying pathology, and response to treatment. APSs include conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). These disorders are characterized by a combination of parkinsonian features and additional symptoms, such as autonomic dysfunction, supranuclear gaze palsy, and asymmetric motor symptoms. Many hypotheses attempt to explain the causes of neurodegeneration in APSs, including interactions between environmental toxins, tau or α-synuclein pathology, oxidative stress, microglial activation, and vascular factors. While extensive research has been conducted on APSs, there is a limited understanding of the symmetry in these diseases, particularly in MSA. Neuroimaging studies have revealed metabolic, structural, and functional abnormalities that contribute to the asymmetry in APSs. The asymmetry in CBS is possibly caused by a variable reduction in striatal D2 receptor binding, as demonstrated in single-photon emission computed tomography (SPECT) examinations, which may explain the disease’s asymmetric manifestation and poor response to dopaminergic therapy. In PSP, clinical dysfunction correlates with white matter tract degeneration in the superior cerebellar peduncles and corpus callosum. MSA often involves atrophy in the pons, putamen, and cerebellum, with clinical symmetry potentially depending on the symmetry of the atrophy. The aim of this review is to present the study findings on potential symmetry as a tool for determining potential neuropsychological disturbances and properly diagnosing APSs to lessen the misdiagnosis rate. Methods: A comprehensive review of the academic literature was conducted using the medical literature available in PubMed. Appropriate studies were evaluated and examined based on patient characteristics and clinical and imaging examination outcomes in the context of potential asymmetry. Results: Among over 1000 patients whose data were collected, PSP-RS was symmetrical in approximately 84% ± 3% of cases, with S-CBD showing similar results. PSP-P was symmetrical in about 53–55% of cases, while PSP-CBS was symmetrical in fewer than half of the cases. MSA-C was symmetrical in around 40% of cases. It appears that MSA-P exhibits symmetry in about 15–35% of cases. CBS, according to the criteria, is a disease with an asymmetrical clinical presentation in 90–99% of cases. Similar results were obtained via imaging methods, but transcranial sonography produced different results. Conclusions: Determining neurodegeneration symmetry may help identify functional deficits and improve diagnostic accuracy. Patients with significant asymmetry in neurodegeneration may exhibit different neuropsychological symptoms based on their individual brain lateralization, impacting their cognitive functioning and quality of life.

Nociplastic Pain: A Critical Paradigm for Multidisciplinary Recognition and Management.

Our understanding of chronic pain has evolved significantly, shifting from a focus on peripheral damage to recognizing the central mechanisms underlying pain perception. This perspective article explores the concept of nociplastic pain, a term introduced by the International Association for the Study of Pain (IASP) in 2017, which describes pain arising from altered pain modulation within the central nervous system, without clear evidence of tissue damage or inflammation. The historical progression from fibrositis to fibromyalgia, and now to nociplastic pain, underscores the complexity of chronic pain syndromes and the need for a multidisciplinary approach to management. Nociplastic pain is characterized by central sensitization, leading to heightened pain sensitivity and often accompanied by comorbidities such as fatigue, sleep disturbances, and cognitive difficulties. Advances in neuroimaging have revealed altered connectivity within key brain networks, such as the default mode and salience networks, in patients with nociplastic pain, providing insights into the neural underpinnings of this condition. The article also addresses controversies surrounding the role of small fiber neuropathy and autonomic dysfunction in nociplastic pain, highlighting the ongoing debates in the field. The practical importance of recognizing nociplastic pain across various medical disciplines-including primary care, orthopedics, neurology, psychiatry, and rheumatology-is emphasized, with recommendations for integrating this knowledge into clinical practice. Emerging therapies, such as neurofeedback, hyperbaric oxygen therapy, and neuromodulation, offer new avenues for treatment, particularly for patients who do not respond to conventional approaches. The article calls for continued research into the mechanisms of nociplastic pain, the development of reliable diagnostic tools, and the exploration of novel therapeutic strategies to improve patient outcomes. The recognition and management of nociplastic pain are crucial for advancing the care of patients with chronic pain, necessitating interdisciplinary collaboration and a patient-centered approach.

Clinical structure and features of the course of pain and non-specific somatoform disorders in adolescent children

Annotation. The research is devoted to the study of clinical signs of painful and nonspecific somatoform disorders in children of early and late adolescence, depending on sex, place of residence, and study. The study examined 56 adolescent children with pain and non-specific syndromes who were treated in the MNP “Khmelnytskyi Regional Children's Hospital” of the Khmelnytskyi Regional Council and in the MP “Khmelnytskyi City Children’s Hospital” of the Khmelnytsky City Council. The average age of the children was 14,0±4,53 years. Among them, children of early adolescence (10-14 years) accounted for 57.2%, and late adolescence (15 years 11 months 28 days) – 42.8%. The clinical signs of pain and nonspecific somatoform disorders in the children we examined were as follows: headache, thermoregulation disorder, fibromyalgia and arthralgia syndrome, nonspecific back pain, asthenic syndrome with decreased work capacity, increased meteorological sensitivity, and impaired concentration. Nonspecific persistent pain syndrome occurred in 56 children, in particular, cephalic pain – in 77.4 %, polyarthralgia – in 8.9%, fibromyalgia syndrome – in 8.5%, nonspecific back pain – in 13.4% of children; thermoregulatory disorders were identified in 42.7%, asthenic syndrome – in 35.3% of children. It shows that among pain somatoform disorders, headache, in particular, tension headache and migraine, occupies the first rank in children. Stress, tension, and sleep disturbances were predominant among the triggering factors. Therefore, among adolescent children with painful and non-specific somatoform disorders, cephalalgia, with a predominance of tension headaches, and long daytime low fevers are most often diagnosed, as a manifestation of autonomic somatoform dysfunctions with impaired thermoregulation. At the same time, migraine, episodic symptoms associated with migraine, as well as trigeminal variants of headache and long-term pain of other localization were found in isolated cases. The age dependence of primary headache has been revealed: tension headaches occur more often in children of early adolescence, and migraines in children of older adolescence, which is important to consider in the differential diagnosis of headaches, since the treatment and prevention of attacks of these forms of headache are completely different.

Results of electrocardiography in children born at very early preterm birth

Background. Children born at extremely early preterm birth (EPL) are at high risk of developing cardiovascular diseases, including heart rhythm disorders (HRDs) and conduction disorders throughout life.Objective: To study electrocardiographic features in children of the first year of life born at term SPR.Materials and methods. The main group consisted of 51 children born at term. Depending on body weight, the main group was divided into 2 subgroups. Subgroup 1 consisted of children weighing 500-750 g (n=15). Subgroup 2 — children weighing 751 g or more (n=36). The comparison group included 28 children born at a gestational age of 32-36 weeks. Children were examined at the ages of 6 and 12 months. Electrocardiography was performed on children at rest in 12 standard leads with a paper tape speed of 50 mm/sec. Analysis of ECG indicators was carried out using a Sicard electrocardiograph from Siemens AG, according to generally accepted methods.Results and discussion. In children born at gestational age during 1 year of life, clinical manifestations of impaired functional state of the cardiovascular system were observed in the form of vegetative-vascular dysfunction, NSR, and changes in the characteristics of heart sounds. According to the ECG results, NSR was identified in the form of sinus arrhythmia, sinus tachy- and bradycardia, extrasystole, atrial rhythm, pacemaker migration, supraventricular paroxysmal tachycardia, WPW syndrome, long QT interval syndrome, which amounted to 86.7% of cases in children of subgroup 1, in children of the 2nd subgroup 82.2% and 60.7% in children of the comparison group. A direct strong correlation has been established between the clinical manifestations of autonomic dysfunctions at the age of 12 months and the frequency of identified dysfunctions. By 12 months of life, the number of children with sinus bradycardia, sinus arrhythmia and ectopic rhythm increases. There is no positive trend in the frequency of detection of ECG phenomena during the first year of life.Conclusion. Children born at very early preterm birth require cardiac monitoring, including blood pressure measurement, electrocardiography and the development of personalized clinical follow-up programs.

Heart rate variability impairment during sleep in Veterans with REM sleep behavior disorder, traumatic brain injury, and posttraumatic stress disorder: An early potential window into autonomic dysfunction?

Comorbid REM sleep behavior disorder (RBD) and neurotrauma (NT, traumatic brain injury + post-traumatic stress disorder; RBD+NT) is associated with increased neurodegenerative symptom burden and worsened health. Sleep and autonomic function are integrally and bidirectionally related to neurodegenerative processes. In the current study, we sought to determine if early signs of autonomic dysfunction, measured via heart rate variability (HRV), were present during sleep in comorbid RBD+NT compared to RBD only and controls. Our data show reduced time and frequency domain HRV during NREM sleep in RBD+NT Veterans compared to RBD only and controls. These data contribute evidence that participants with RBD and comorbid NT demonstrate significantly worse autonomic dysfunction compared to age/sex matched participants with RBD alone.

Hypertension and its correlation with autonomic nervous system dysfunction, heart rate variability and chronic inflammation

Objective This study investigates the relationship between hypertension, dysregulation of the autonomic nervous system, heart rate variability (HRV), and chronic inflammation. Methods We analysed a cohort of 50 hypertensive patients treated at the affiliated Hospital of Jianghan University. The average systolic and diastolic blood pressures (BPs) in this group were 155.26 and 95.32 mmHg, respectively. A control group of 50 healthy volunteers, undergoing routine physical examinations at the same hospital, was also analysed. Results The average systolic BP of the control group was 115.64 ± 10.27 mmHg, and the average diastolic BP was 75.33 ± 8.25 mmHg. In contrast, the experimental group exhibited an average systolic BP of 155.26 ± 20.13 mmHg and an average diastolic BP of 95.32 ± 12.16 mmHg. Both systolic and diastolic BPs were significantly higher in the hypertensive group (p < 0.05). The experimental group also demonstrated reduced HRV and skin conductance response, alongside increased BP variability (BPV), urinary epinephrine levels and prolonged pupillary light reaction time compared to controls (p < 0.05). Notably, Standard Deviation of Normal to Normal Intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD) values were significantly lower in the experimental group (p < 0.05). Furthermore, levels of inflammatory markers such as CRP, TNF-α, IL-6 and IL-1β were markedly elevated in hypertensive patients (p < 0.05). Negative correlations were observed between systolic and diastolic BP with HRV metrics, while positive correlations were found between BP and BPV as well as urinary adrenaline levels. Conclusions The findings indicate that hypertension is closely associated with autonomic nervous system dysfunction, reduced HRV and increased chronic inflammation. A comprehensive approach to hypertension management should integrate these interrelated physiological and pathological mechanisms, with potential therapeutic interventions targeting autonomic function and inflammatory states.

The Impact of Antidepressants on COVID-19 and Post-Acute COVID-19 Syndrome: A Scoping-Review Update

On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses. COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue. Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.

Temporal Pattern of Individual Neurological Function Recovery in Guillain-Barré Syndrome.

Background: There is paucity of studies on the temporal pattern of recovery of facial, bulbar, sensory, motor, and autonomic dysfunction in Guillain-Barré syndrome (GBS), although many studies have reported short- and long-term functional outcomes. We report the temporal pattern of recovery of various neurological functions in GBS, and compare the pattern of recovery between acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Methods: Forty-two patients with GBS were prospectively included, and their clinical details, including peak disability on a 0-6 scale, were noted. The day of complete recovery in motor, sensory, facial, bulbar, and autonomic functions during 3 months of follow-up was recorded. Results: Complete recovery of autonomic function occurred in all (median, 12 days), bulbar weakness in 91.3% (median, 15 days), facial weakness in 86.2% (median, 19 days), and sensory functions in 82.1% (median, 20 days). Only 9.5% of patients achieved normal motor function within 3 months. The days of complete recovery of bulbar, facial, autonomic, and motor deficits were comparable between AIDP and AMAN. Demyelinating GBS had an earlier recovery of bulbar and sensory functions. Conclusions: The neurological recovery in GBS occurs first in the autonomic, followed by the bulbar, facial, sensory, and motor functions. The demyelinating type had an earlier recovery of bulbar and sensory functions.