Insight of autonomic dysfunction in CLN3 disease: a study on episodes resembling paroxysmal sympathetic hyperactivity (PSH).

BACKGROUND: Recurrent non-epileptic episodes resembling paroxysmal sympathetic hyperactivity (PSH) have been observed in adolescents with Juvenile Ceroid Lipofuscinosis (CLN3-disease) and a possible association to an autonomic dysfunction has been suggested. The objective of the present study was to investigate the dynamics of the autonomic activity up to, during, and in the time after individual attacks. We include all seven suitable CLN3 patients in Denmark ≥ 15 years of age. HRV parameters were assessed from continuous heart rate monitoring during seven consecutive days and a particular focus of HRV parameters was obtained in close temporal context to clinically recurrent PSH-like episodes. In addition, the likelihood of PSH was assessed by caregiver's description and by video documentation. RESULTS: Respectively eight and five episodes were recorded in two patients (18 and 20 years of age). The episodes were all safely superior to the cut off values of the clinical assessment score to be considered PSH-like episodes. During all 13 episodes, HRV revealed a statistically significant decrease in root mean square of successive differences (RMSSD) and standard deviation of the Poincaré-Plot interval (SD1) in the minutes prior to the clinical onset of the episodes, both indicating a sudden decrease in parasympathetic activity in advance of the onset. The reduced activity remained low during the episodes, and 15-30 min following the attack cessation, the parasympathetic activity had returned to pre-attacks levels. The sympathetic HRV parameters were unchanged resulting in a sympathetic overactivity during the episodes. In a third participant (32 years of age), in whom severity of PSH-like episodes had been gradually reduced during the last years, five episodes were registered. A similar temporally related reduction of the parasympathetic activity was found, but because the sympathetic activity decreased as well, no sympathetic dominance developed, which most reasonable is the reason to the clinically reduced expression of the episodes. CONCLUSION: The documented transient withdrawal of parasympathetic activity leading to a paroxysmal unbalanced sympathetic hyperactivity most probably accounts for the PSH-like episodes occurring in post-adolescent CLN3 patients. The findings shed new light on both aetiology and possible preventative and therapeutic measures.

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

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

BACKGROUND: Chronic 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 PRESENTATION: The 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. CONCLUSIONS: We 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.

Heart Rate Variability and Global Longitudinal Strain for Prognostic Evaluation and Recovery Assessment in Conservatively Managed Post-Myocardial Infarction Patients.

Background: Heart rate variability (HRV) is the fluctuation in the time intervals between adjacent heartbeats. HRV is a measure of neurocardiac function that is produced by dynamic autonomic nervous system (ANS) processes and is a simple measure that estimates cardiac autonomic modulation. Methods: The study included 108 patients admitted to the Coronary Intensive Care Unit with acute myocardial infarction (AMI) who did not undergo primary percutaneous transluminal coronary angioplasty (PTCA) or systemic thrombolysis and followed conservative management. All patients underwent detailed clinical, biological, and paraclinical assessments, including evaluation of HRV parameters and echocardiographic measurements. The analysis of RR variability in both time and frequency domains indicates that the negative prognosis of patients with AMI is associated with an overall imbalance in the neuro-vegetative system. The HRV parameters were acquired using continuous 24 h electrocardiogram (ECG) monitoring at a baseline, after 1 month, and 6 months. Results: Our analysis reveals correlations between alterations in HRV parameters and the increased risk of adverse events and mortality after AMI. The study found a significant improvement in HRV parameters over time, indicating better autonomic regulation post-AMI. The standard deviation of all RR intervals (SDNN) increased significantly from baseline (median 75.3 ms, IQR 48.2-100) to 1 month (median 87 ms, IQR 55.7-111) and further to 6 months (median 94.2 ms, IQR 67.6-118) (p < 0.001 for both comparisons). The root mean square of successive difference of RR (RMSSD) also showed significant increases at each time point, from baseline (median 27 ms, IQR 22-33) to 1 month (median 30.5 ms, IQR 27-38) and from 1 month to 6 months (median 35 ms, IQR 30-42) (p < 0.001 for all comparisons), indicating enhanced parasympathetic activity. Moreover, changes in HRV parameters have been associated with impaired left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS), indicating a relationship between autonomic dysfunction and myocardial deformation. GLS values improved from a baseline median of -11% (IQR 5%) to -13% (IQR 4%) at 6 months (p < 0.001), reflecting better myocardial function. Conclusions: HRV parameters and cardiac performance analysis, especially using GLS, offer a solid framework for evaluating recovery and predicting adverse outcomes post-MI.

An overview of Ehlers Danlos syndrome and the link between postural orthostatic tachycardia syndrome and gastrointestinal symptoms with a focus on gastroparesis.

There has been an increasingly reported association between Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS) and gastrointestinal disorders. EDS is a hereditary connective tissue disorder which may manifest as a spectrum of symptoms stemming from collagen defects. The prevalence of EDS is estimated to affect 1 in 5000 individuals which underscores its clinical significance. Notably the hypermobile form (hEDS) accounts for the majority of cases. POTS is characterized by orthostatic intolerance with an increase in heart rate on standing in the absence of hypotension. This condition predominantly affects women between 15 and 45 years of age. Gastrointestinal symptoms in the form of reflux, bloating and abdominal pain significant impact this population. Gastroparesis is a chronic disorder involving symptoms of delayed gastric emptying and may be closely associated with hEDS and POTS, and may be underreported. Autonomic dysfunction associated with hEDS has been proposed as the likely mechanism underlying POTS and gastrointestinal dysfunction though a clear pathophysiological process has not been established.

Cardiac implications in myasthenia gravis.

This editorial aimed to consolidate the current evidence in literature on the association between myasthenia gravis (MG) and cardiac involvement, focusing on the impact of thymoma, antistriational antibodies, and late-onset MG. Additionally, the study aimed to explore the influence of genetic differences among populations on the association with cardiac disease. We conducted a review of existing literature in PubMed and Google Scholar to find relevant studies on cardiac involvement in MG. We created search criteria using a combination of free text words, including MG, antistriational antibodies, thymectomy, cardiomyopathy, myocarditis, arrhythmias, autonomic dysfunction. Relevant articles published in English language were analyzed and incorporated. The findings indicate a strong association between thymoma, myasthenic crisis, antistriational antibodies, and late-onset MG with cardiac involvement. The study also revealed that genetic differences among populations influence the risk of cardiac disease and electrocardiography (ECG) abnormalities in MG patients. Autonomic dysfunctions altered cardiac autonomic response and increased susceptibility to arrhythmias and sudden cardiac death in MG patients. The study supports the significance of thymoma, antistriational antibodies, and late-onset MG as key factors associated with cardiac involvement in MG patients. It emphasizes the importance of ECG as the initial test in managing MG patients, particularly in the perioperative period, to identify and genetic testing if needed to address their cardiac risk effectively.

Autonomic dysfunction as a possible cause of sudden cardiac death in swimming sports.

Introduction: Human diving reflex is a well-studied phenomenon. However, very little is known about the possible relationship between augmented diving reflex and autonomic dysfunction. Methods: We retrospectively studied a group of four swimmers who underwent a diving reflex test as part of the examination due to symptoms related to autonomic dysfunction during swimming. The control group comprised 11 healthy swimmers with no history of these symptoms. A standardized diving reflex test was performed for each athlete in both groups. Hemodynamic profiles, including heart rate, stroke volume, and cardiac output, were recorded. Results: There were no statistically significant differences between the groups in any of the three parameters measured before the test. However, at the end of the test, each parameter (heart rate, stroke volume, and cardiac output) was significantly lower in the swimmers who presented with clinical symptoms related to autonomic dysfunction than in the control group. Conclusion: This observation could shed light on autonomic dysfunction as a possible cause of sudden cardiac death in swimming athletes. It also demonstrated that autonomic dysfunction is presented not only by decreased heart rate but also by stroke volume, causing a drop in cardiac output to the level of hemodynamic collapse.

Exacerbation of symptoms, nocturnal acid reflux, and impaired autonomic function are associated with sleep disturbance in gastroesophageal reflux disease patients.

Background and aim: Gastroesophageal reflux disease (GERD) patients often report sleep disturbance (SD); however, the relationship between GERD and SD is unknown. This study investigated whether SD affects symptoms, acid reflux, and autonomic function in GERD patients. Methods: A total of 257 subjects (126 patients with SD and 99 patients without SD) participated in this survey from January 2020 to August 2022. Participants were required to complete questionnaires including the GERD impact scale (GIS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Esophageal mucosal injury, acid exposure, peristaltic function, and autonomic function were assessed by upper endoscopy, high-resolution esophageal manometry (HRAM), 24-h multichannel intraluminal impedance with pH (24 h-MII-pH), and electrocardiography (ECG). Results: Gastroesophageal reflux disease patients with SD experienced a higher frequency of prolonged reflux (p < 0.001), longest reflux event (p < 0.001), acid exposure time (p < 0.001) during the recumbent period, and a higher incidence of erosive esophagitis (EE) (59.5 vs. 45.5%, p = 0.036) than those without SD. Pearson's correlation analysis showed that SD was positively correlated with GIS (r = 0.725, p < 0.001), HAMA (r = 0.680, p < 0.001), and HAMD (r = 0.323, p < 0.001) scores, and negatively correlated with parasympathetic or vagal nerve activity (r = -0.770, p < 0.001). Conclusion: Gastroesophageal reflux disease patients with SD experience more severe reflux symptoms and nocturnal acid reflux, which may be related to autonomic dysfunction.

Responses to Valsalva's maneuver in spinal cord injury do not broadly relate to vasoconstrictor capacity.

PURPOSE: A blood pressure stabilization during late phase II of Valsalva's maneuver may be utilized to confirm sympathetic vasoconstrictor control after a spinal cord injury. This study investigated whether Valsalva response was predictive of hemodynamics during tilt or isometric handgrip. METHODS: Presence/absence of Valsalva response was compared to heart rate, mean arterial pressure, leg blood flow, and vascular resistance during head-up tilt and isometric handgrip to fatigue in 14 adults with spinal cord injury from C7 to T12 and 14 controls. Statistics were performed with two-way repeated measure analysis of variance (ANOVA), post hoc t-tests for between-group comparisons, and Mann-Whitney U tests for within-group. RESULTS: In total, six participants with spinal cord injury lacked a blood pressure stabilization for Valsalva's maneuver. However, this was not related to vasoconstrictor responses during the other tests. The groups had similar heart rate and blood pressure changes during tilt, though leg blood flow decreases and vascular resistance increases tended to be smaller at 20° tilt in those with spinal cord injury (p = 0.07 and p = 0.11, respectively). Participants with spinal cord injury had lower heart rates and markedly smaller blood pressure increases during handgrip (both p < 0.05). There were no group differences in leg blood flow, but those with spinal cord injury demonstrated a blunted vascular resistance increase by the final 10% of the handgrip (p < 0.01). CONCLUSIONS: Valsalva response was not consistent with hemodynamics during other stimuli, but some individuals evidence increases in sub-lesional vascular resistance to isometric handgrip comparable to controls, suggesting a sympathoexcitatory stimulus may be critical to provoke hemodynamic responses after spinal cord injury.

Concurrent Oncolysis and Neurolesion Repair by Dual Gene-Engineered hNSCs in an Experimental Model of Intraspinal Cord Glioblastoma.

Intramedullary spinal cord glioblastoma (ISCG) is lethal due to lack of effective treatment. We previously established a rat C6-ISCG model and the antitumor effect of F3.CD-TK, an hNSC line expressing CD and TK, via producing cytocidal 5FU and GCV-TP. However, the neurotherapeutic potential of this hNSC approach has remained uninvestigated. Here for the first time, cultured F3.CD-TK cells were found to have a markedly higher oncolytic effect, which was GJIC-dependent, and BDNF expression but less VEGF secretion than F3.CD. In Rowett athymic rats, F3.CD-TK (1.5 × 106 cells/10 µL × 2), injected near C6-ISCG (G55 seeding 7 days earlier: 10 K/each) and followed by q.d. (×5/each repeat; i.p.) of 5FC (500 mg/kg/5 mL/day) and GCV (25 mg/kg/1 mL/day), robustly mitigated cardiorespiratory, locomotor, and sensory deficits to improve neurofunction and overall survival compared to animals receiving either F3.CD or F3.CD-TK+F3.CD debris formula. The F3.CD-TK regimen exerted greater tumor penetration and neural inflammation/immune modulation, reshaped C6-ISCG topology to increase the tumor's surface area/volume ratio to spare/repair host axons (e.g., vGlut1+ neurites), and had higher post-prodrug donor self-clearance. The multimodal data and mechanistic leads from this proof-of-principle study suggest that the overall stronger anti-ISCG benefit of our hNSC-based GDEPT is derived from its concurrent oncolytic and neurotherapeutic effects.

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality. METHODS: Forty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests. RESULTS: Among the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups. CONCLUSIONS: We have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.

Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course. METHODS: We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort. RESULTS: Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5 years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it. CONCLUSION: TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.

Cellular and Molecular Mechanisms Underlying Altered Excitability of Cardiac Efferent Neurons in Cirrhotic Rats.

Patients with cirrhosis often exhibit cardiac autonomic dysfunction (CAD), characterized by enhanced cardiac sympathetic activity and diminished cardiac vagal tone, leading to increased morbidity and mortality. This study delineates the cellular and molecular mechanisms associated with altered neuronal activities causing cirrhosis-induced CAD. Biliary and nonbiliary cirrhotic rats were produced by common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Three weeks after CBDL or TAA injection, the assessment of heart rate variability revealed autonomic imbalance in cirrhotic rats. We observed increased excitability in stellate ganglion (SG) neurons and decreased excitability in intracardiac ganglion (ICG) neurons in cirrhotic rats compared to sham-operated controls. Additionally, threshold, rheobase, and action potential duration exhibited opposite alterations in SG and ICG neurons, along with changes in afterhyperpolarization duration. A- and M-type K⁺ channels were significantly downregulated in SG neurons, while M-type K⁺ channels were upregulated, with downregulation of the N- and L-type Ca2⁺ channels in the ICG neurons of cirrhotic rats, both in transcript expression and functional activity. Collectively, these findings suggest that cirrhosis induces an imbalance between cardiac sympathetic and parasympathetic neuronal activities via the differential regulation of K+ and Ca2+ channels. Thus, cirrhosis-induced CAD may be associated with impaired autonomic efferent functions within the homeostatic reflex arc that regulates cardiac functions.

Heart Rate Variability and Functional Outcomes of Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients. METHODS: We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0-2, 0-8, 0-12, 0-24, 0-48, 0-72, and 8-16, 16-24, 24-48, 48-72, 72-96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0-2. RESULTS: The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0-72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0-72 h: OR 0.898; CI 0.800-1.008; p = 0.067). CONCLUSIONS: Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days.

Orthostatic Vital Signs After Sport-Related Concussion: A Cohort Study.

BACKGROUND: The 6th International Consensus Statement on Concussion in Sport guidelines identified that measuring autonomic nervous system dysfunction using orthostatic vital signs (VSs) is an important part of the clinical evaluation; however, there are limited data on the frequency of autonomic nervous system dysfunction captured via orthostatic VSs after concussion. PURPOSE: To compare orthostatic changes in heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between athletes with acute sport-related concussion (SRC) and control athletes. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We compared 133 athletes (mean age, 15.3 years; age range, 8-28 years; 45.9% female) with acute SRC (<30 days after injury) with 100 control athletes (mean age, 15.7 years; age range, 10-28 years; 54.0% female). Given the broad age range eligible for study inclusion, participants were subdivided into child (younger than 13 years of age), adolescent (13-17 years of age), and adult (18 years of age and older) age groups for subanalyses. Participants completed a single standard orthostatic VS evaluation including HR, SBP, and DBP in the supine position then immediately and 2 minutes after standing. Linear regression was used to compare delayed supine-to-standing changes in HR, SBP, and DBP as a continuous variable (ΔHR, ΔSPB, and ΔDBP) between groups, and logistic regression was used to compare patients with positive orthostatic VS changes (sustained HR increase ≥30 beats per minute [bpm], SBP decrease ≥20 mm Hg, and DBP ≥10 mm Hg at 2 minutes) between groups, accounting for age and sex. RESULTS: Between-group differences were present for delayed ΔHR (18.4 ± 12.7 bpm in patients with SRC vs 13.2 ± 11.0 bpm in controls; P = .002) and ΔSPB (-3.1 ± 6.6 bpm in patients with SRC vs -0.4 ± 6.5 bpm in controls; P = .001), with positive orthostatic HR changes present more frequently in patients with SRC (18% vs 7%; odds ratio, 2.79; P = .027). In the SRC group, a weak inverse relationship was present between age and ΔHR (r = -0.171; P = .049), with positive orthostatic HR findings occurring primarily in the child and adolescent SRC subgroups. CONCLUSION: Patients with acute SRC had greater orthostatic VS changes compared with controls, the most prominent being sustained HR elevations. Clinical evaluation of autonomic change after SRC via standard orthostatic VS assessment may be a helpful clinical biomarker in the assessment of SRC, especially in children and adolescents.

Multiple sclerosis and amyotrophic lateral sclerosis: is there an association or a red flag? A case report and literature review.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that causes damage to the myelin and axons and is caused by genetic or environmental factors. Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive degeneration of the motor neurons resulting in the presence of upper and lower motor-neuron signs and symptoms. CASE PRESENTATION: A 46-year-old female patient presented with symmetrical weakness of the lower limbs and numbness that developed over weeks. Magnetic resonance imaging (MRI) of the brain exhibited typical demyelination features, high signal abnormality involving the periventricular and subcortical white matter, and an oval-shaped lesion. The patient was diagnosed with MS based on the clinical presentation and radiological examination. However, there was rapid progression of the symptoms, involvement of bulbar dysfunction, and muscle atrophy. Furthermore, the patient did not respond to acute therapy and immunotherapy, which made the diagnosis of MS less likely or suggested that it could be associated with another diagnosis. Her neurophysiological test met the criteria of ALS, and she was started on riluzole. LITERATURE REVIEW: We reviewed all articles from 1986 to 2023, and there were 32 reported cases describing the co-occurrence of ALS and MS in different populations. Our case is the 33rd, and to our knowledge, it is the only case reported in the Middle East and specifically in Saudi Arabia. The main proposed mechanism according to postmortem examinations is a combination of degenerative and inflammatory processes with a cascade of production of reactive oxygen species and nitric oxide, which lead to cell death and apoptosis during concomitant ALS with MS. CONCLUSION: The co-occurrence of ALS and MS is extremely rare, but it can be explained by pathogenesis related to neurodegeneration, inflammation, or genetic susceptibility. Rapid progressive motor and bulbar symptoms could be red-flag symptoms, extensive evaluation might be needed for these patients.

Autonomic Dysfunction and Cardiac Performance in Pregnant Women with Hypertensive Disorders: A Comparative Study Using Heart Rate Variability and Global Longitudinal Strain.

(1) Background: Pregnancy induces significant physiological adaptations with substantial impacts on the cardiovascular system. Hypertensive disorders of pregnancy (HDPs) are connected to significant risks of maternal and fetal complications, contributing significantly to morbidity and mortality across the globe. This study focuses on evaluating autonomic dysfunction by analyzing heart rate variability (HRV) and assessing cardiac performance through global longitudinal strain (GLS) using speckle tracking echocardiography, as well as examining diastolic function in pregnant women with HDP compared to healthy pregnant controls. (2) Methods: A case-control study was conducted involving pregnant women diagnosed with gestational hypertension (GH), preeclampsia (PE), or severe preeclampsia (SPE) as the case group, and healthy pregnant women as the control group. HRV was measured to evaluate autonomic function, GLS was assessed using speckle tracking echocardiography, and diastolic function was evaluated through standard echocardiographic parameters. Data were analyzed to compare cardiac performance and autonomic regulation between the HDP and control group, as well as among the different HDP subgroups. (3) Results: The HDP group exhibited significantly reduced HRV parameters compared to healthy controls, indicating notable autonomic dysfunction. Speckle tracking echocardiography revealed lower GLS among women with HDP, particularly in those with SPE, compared to the control group. Diastolic dysfunction was also present in the HDP group. (4) Conclusions: HRV and GLS are valuable non-invasive tools for detecting autonomic dysfunction and cardiac performance impairments in pregnant women with hypertensive disorders. These findings suggest that autonomic and cardiac dysfunctions are prevalent in HDP.

A Cross-Sectional Study of Cardiovascular Autonomic Reactivity in Ehlers-Danlos Syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) may be linked to dysfunction in the autonomic nervous system, affecting collagen production and processing. These collagen abnormalities lead to a condition called dysautonomia. Findings underscore the need for further investigation into autonomic nervous system function in EDS which involves larger studies to strengthen the evidence of non-invasive screening tools like cardiovascular reflex tests. These tests might offer a valuable way to assess an individual's risk for future complications. OBJECTIVE: This study aimed to assess autonomic reactivity in EDS patients using cardiovascular reflex tests. METHODS: This study was conducted at the Department of Physiology, Naraina Medical College and Research Centre, Kanpur (Uttar Pradesh). The cardiovascular reflex test was used to identify 60 individuals, 30 of whom were EDS patients and 30 were healthy controls, with a common age limit of 18-25 years. Cardiovascular reflex tests, such as the delta heart rate, lying-to-standing test (LST), deep breathing test (DBT), and Valsalva maneuver, were performed and recorded for each subject. IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States) was used for the compilation and analysis of data. RESULTS: The expiration-to-inspiration (E:I) ratio and delta heart rate of the EDS patients both significantly decreased as compared to the healthy control group (1.10±0.02 versus 1.22±0.77 and 14.03±0.31 versus 15.52±0.32). The Valsalva ratio of the EDS patients decreased (1.28±0.01) as compared to the healthy control group (1.46±0.01), which was statistically significant. The 30:15 ratio in the EDS patients was significantly decreased compared to the healthy control group (1.08±0.01 versus 1.15±0.01). The handgrip test and cold pressor test results were statistically insignificant. CONCLUSION: The study suggests a connection between EDS and autonomic nervous system dysfunction, causing symptoms like tachycardia and hypotension. It recommends exploring non-invasive cardiovascular reflex tests as a tool to identify autonomic dysfunction in EDS patients and predict long-term cardiovascular complications. These tests offer valuable insights into autonomic function.