UNASSIGNED: The autonomic nervous system (ANS) is cardinal for systemic homeostasis. Autonomic dysfunction is prevalent in as high as 65% of patients presenting for cardiac surgery in the Indian scenario. Pre-existing cardiac autonomic dysfunction (CAD) in surgical patients can accentuate perioperative haemodynamic fluctuations during stressful intraoperative events, predispose to adverse cardiac events, and contribute to morbidity and mortality. The prevalence and predictors of CAD in the elective neurosurgical population are unknown in the Indian scenario. The current study was conducted to bridge this knowledge gap.
UNASSIGNED: In this single-centre prospective observational study conducted at a tertiary care neurosciences centre, among 400 consenting adult patients of either gender, between 18 and 80 years of age, undergoing elective neurosurgery, the preoperative ANS function at the bedside was assessed as the primary outcome measure. The ANS status was evaluated using ANSiscope™-derived indices of heart rate variability. The diagnosis of CAD was made when the ANS index exceeded a threshold of 13.5. Data regarding predictors of CAD were collected from patient records as the secondary outcome measure. Statistical analysis was done using the R software. A P-value of <0.05 was considered statistically significant.
UNASSIGNED: The prevalence of preoperative CAD in our study population was 79.7% (319/400 patients). None of the demographic and baseline clinical characteristics we studied predicted CAD in our study.
UNASSIGNED: We observed a significant prevalence of preoperative CAD among elective neurosurgical patients. None of the parameters we evaluated predicted CAD in our study.

OBJECTIVE: To investigate hypothalamic atrophy and its clinical correlates in multiple system atrophy (MSA) in-vivo.
BACKGROUND: MSA is characterized by autonomic dysfunction and parkinsonian/cerebellar manifestations. The hypothalamus regulates autonomic and homeostatic functions and is also involved in memory and learning processes.
METHODS: 11 MSA, 18 Parkinson\'s Disease (PD) and 18 Healthy Controls (HC) were included in this study. A validated and automated hypothalamic segmentation tool was applied to 3D-T1-weighted images acquired on a 3T MRI scanner. MSA hypothalamic volumes were compared to those of PD and HC. Furthermore, the association between hypothalamic volumes and scores of autonomic, depressive, sleep and cognitive manifestations were investigated.
RESULTS: Posterior hypothalamus volume was reduced in MSA compared to controls (t = 2.105, p = 0.041) and PD (t = 2.055, p = 0.046). Total hypothalamus showed a trend towards a reduction in MSA vs controls (t = 1.676, p = 0.101). Reduced posterior hypothalamus volume correlated with worse MoCA scores in the parkinsonian (MSA + PD) group and in each group separately, but not with autonomic, sleep, or depression scores.
CONCLUSIONS: In-vivo structural hypothalamic involvement may be present in MSA. Reduced posterior hypothalamus volume, which includes the mammillary bodies and lateral hypothalamus, is associated with worse cognitive functioning. Larger studies on hypothalamic involvement in MSA and its clinical correlates are needed.

OBJECTIVE: To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state.
METHODS: A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests.
RESULTS: In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process.
CONCLUSIONS: Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.

OBJECTIVE: Biofeedback is a therapeutic treatment model that teaches self-regulation of autonomic functions to alleviate stress-related symptoms. \"Long COVID\" refers to chronic physical and cognitive sequelae post-SARS-CoV-2 infection. This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID.
METHODS: Data were collected from 20 adult participants aged 22-63 (Mage = 44.1, SDage = 12.2) with varying long COVID symptoms. Within this single arm design, 16 of the 20 participants completed all six sessions of biofeedback; 14 completed an assessment at the three-month post-treatment time point.
RESULTS: Participants self-reported significant improvements in somatic, anxiety, and depressive symptoms, sleep quality, quality of life, and number of \"bad days\" immediately after the intervention and three months later (Cohen\'s d effect size (ES) = 1.09-0.46). Reduced number of medical doctor visits (ES = 0.85) and prescription drug use over the last month (odds ratio = 0.33), as well as improved emotional wellbeing (ES = 0.97) were observed at the three-month time point only.
CONCLUSIONS: Results suggest that this short, readily scalable intervention can be potentially efficacious in alleviating symptoms of long COVID. Despite notable improvements, the major limitation of this study is its lack of control group. While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection.
RESULTS: govID: NCT05120648.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants\' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS).
POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted.
This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion.
A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups.
This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

UNASSIGNED: Post-COVID-19 syndrome, or Long Covid (LC) refers to symptoms persisting 12 weeks after the COVID-19 infection. LC comprises a wide range of dysautonomia symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. This study tested the feasibility and estimated the efficacy, of a Heart Rate Variability Biofeedback (HRV-B) programme via a standardised slow diaphragmatic breathing technique in individuals with LC.
UNASSIGNED: LC patients underwent a 4-week HRV-B intervention for 10 minutes twice daily for 4 weeks using the Polar H10 ECG (Electrocardiogram) chest strap and Elite HRV phone application. Outcome measures C19-YRSm (Yorkshire Rehabilitation Scale modified), Composite Autonomic Symptom Score (COMPASS-31), WHO Disability Assessment Schedule (WHODAS), EQ5D-5L (EuroQol 5 Dimensions) and Root Mean Square of Successive Differences between heartbeats (RMSSD) using a Fitbit device were recorded before and after the intervention. The study was pre-registered at clinicaltrials.gov NCT05228665.
UNASSIGNED: A total of 13 participants (54% female, 46% male) completed the study with high levels of independent use of technology, data completeness and intervention adherence. There was a statistically significant improvement in C19YRS-m (P = .001), COMPASS-31 (P = .007), RMSSD (P = .047), WHODAS (P = .02) and EQ5D Global Health Score (P = .009). Qualitative feedback suggested participants could use it independently, were satisfied with the intervention and reported beneficial effects from the intervention.
UNASSIGNED: HRV-B using diaphragmatic breathing is a feasible intervention for LC. The small sample size limits generalisability. HRV-B in LC warrants further exploration in a larger randomised controlled study.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease. It has a fast progression, so early diagnosis is decisive. Two functional imaging tests can be involved in its diagnosis: [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. Our aim is to comparatively analyze the diagnostic performance of both techniques.
METHODS: 46 patients (24 males and 22 females) with MSA underwent [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. In each of these techniques, qualitative assessment was compared with quantitative assessment.
RESULTS: SPECT visual assessment was positive in 93.5% of subjects (S = 95.24%; PPV = 93.02%). A cut-off of 1.363 was established for overall S/O index (S = 85.7%, E = 100%). Visual assessment of scintigraphy was positive in 73.1% (S = 78.57%, PPV = 94.29%). For the delayed heart/medistinum ratio (HMR) a cut-off of 1.43 (S = 85.3, E = 100%) was obtained. For each unit increase in delayed HMR, the suspicion of MSA increased by 1.58 (OR = 1.58, p < 0.05). The quantitative assessment showed an association with the visual assessment for each technique (p < 0.05).
CONCLUSIONS: Both tests are useful in MSA diagnosis. Comparatively, we did not observe a clear superiority of either. Striatal and myocardial deterioration do not evolve in parallel. Qualitative assessment is crucial in both techniques, together with the support of quantitative analysis. Delayed HMR shows a direct relationship with the risk of MSA.

BACKGROUND: Multiple system atrophy (MSA) is subdivided into two types: MSA-P (parkinsonian) and MSA-C (cerebellar). Brain SPECT allows for the detection of nigrostriatal involvement, even in the early stages. To date, the scientific literature does not show a consensus on how to follow-up MSA, especially MSA-C. Our aim was to analyze the diagnostic effectiveness of repeat [123I]Ioflupane SPECT for the follow-up of MSA.
METHODS: A longitudinal observational study on 22 MSA patients (11 males and 11 females).
RESULTS: Significant changes were obtained in the quantitative SPECT assessments in the three Striatum/Occipital indices. The qualitative SPECT diagnosis did not show differences between the initial and evolving SPECT, but the neurologist\'s clinical suspicion did. Our results showed a brain deterioration of around 31% at 12 months, this being the optimal cut-off for differentiating a diseased subject (capable of solving diagnostic error rate). Previous imaging tests were inconclusive, as they showed less deterioration in the SPECT and quantitative assessments with respect to the group of confirmed patients. Repeated SPECT increased the diagnostic sensitivity (50% vs. 75%) and positive predictive value (72.73% vs. 77%). In addition, repeated SPECT proved decisive in the diagnosis of initial inconclusive cases.
CONCLUSIONS: Repeat SPECT at 12 months proves useful in the diagnosis and follow-up of MSA.

BACKGROUND: Reduced preload and thoracic blood volume accompany postural tachycardia syndrome (POTS). Head-down tilt (HDT) increases both preload and intrathoracic blood volume. The objective of this study was to assess the safety and efficacy of HDT in POTS in acute settings.
METHODS: This retrospective study evaluated POTS patients. Analyzed data included heart rate, blood pressure, cerebral blood flow velocity (CBFv) in the middle cerebral artery, and capnography. The baseline supine hemodynamic data were compared with the data obtained at the second minute of the -10° HDT. A linear mixed-effects model was used to assess the effect of HDT on hemodynamic variables.
RESULTS: The HDT was explored in seven POTS patients and an additional seven POTS patients without HDT served as controls. In the HDT arm, four POTS patients had overlapping diagnoses of myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) and one patient had comorbidity of post-acute sequelae of SARS-CoV-2 infection (PASC). HDT lowered heart rate by 10% and increased end-tidal CO2 by 8%. There was no change in other cardiovascular variables.
CONCLUSIONS: In the acute setting, HDT is safe. HDT reduces the heart rate presumably by modulating baroreflex by enhancing preload and stroke volume, which in turn increases thoracic blood volume with a net effect of parasympathetic cardiovagal activation and/or sympathetic withdrawal. This pilot study provides a foundation to proceed with longitudinal studies exploring the long-term effect of repetitive HDT in conditions associated with preload failure such as POTS, ME/CSF, and PASC.