Dysautonomic Symptoms Research Articles

The Impact of Cannabidiol Treatment on Anxiety Disorders: A Systematic Review of Randomized Controlled Clinical Trials.

Generalized Anxiety Disorder (GAD) is a common psychiatric condition characterized by persistent and excessive worry, often accompanied by dysautonomic symptoms that significantly impact patients' well-being. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has shown potential as an anxiolytic through its partial agonism of the 5HT-1A receptor and its negative allosteric modulation of CB1 receptors, which may help mitigate the anxiogenic effects of tetrahydrocannabinol (THC). This study evaluates the impact of CBD on individuals diagnosed with various anxiety disorders, comparing its effects to placebo and conventional pharmaceutical treatments through a systematic review of randomized controlled trials (RCTs). A systematic search of RCTs published between 2013 and 2023 was conducted across three databases using the terms "cannabidiol" and "anxiety". Out of the 284 articles identified, 11 met the eligibility criteria. The studies reviewed varied widely in terms of the types of anxiety disorders and CBD dosages examined, leading to results that were often contradictory. Despite these conflicting outcomes, the data suggest that CBD may reduce anxiety with minimal adverse effects when compared to a placebo. However, further RCTs with improved methodologies, encompassing a broad range of doses and continuous CBD administration across specific anxiety disorders, are needed. Unlike previous studies and meta-analyses, this review encompasses a broader spectrum of anxiety disorders and a variety of study designs and dosages, providing a more nuanced understanding of CBD's potential efficacy across different conditions.

Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review).

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of β-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.

Beyond pain: Using Unsupervised Machine Learning to Identify Phenotypic Clusters of Small Fiber Neuropathy.

Small fiber neuropathy (SFN) is characterized by dysfunction and loss of peripheral unmyelinated and thinly myelinated nerve fibers, resulting in a phenotype that includes varying combinations of somatosensory and dysautonomia symptoms, which can be profoundly disabling and lead to decreased quality of life. Treatment aimed mainly at pain reduction, which may not target the underlying pathophysiology, is frequently ineffective. Another impediment to the effective management of SFN may be the significant between-patient heterogeneity. Accordingly, we launched this study to gain insights into the symptomatic variability of SFN and determine if SFN patients can be sub-grouped based on clinical characteristics. To characterize the phenotype and investigate how patients with SFN differ from those with large fiber involvement, 105 patients with skin-biopsy proven SFN and 45 with mixed fiber neuropathy (MFN) were recruited. Using unsupervised machine learning, SFN patients were clustered based upon symptom concurrence and severity. Demographics, clinical data, symptoms, and skin biopsy- and laboratory findings were compared between the groups. MFN- as compared to SFN patients, were more likely to be male, older, had a lower intraepidermal nerve fiber density at the ankle and more frequent abnormal immunofixation. Beyond these differences, symptom prevalence and intensities were similar in the two cohorts. SFN patients comprised three distinct phenotypic clusters, which differed significantly in symptom severity, co-occurrence, localization, and skin biopsy findings. Only one subgroup, constituting about 20% of the patient population, was characterized by intense neuropathic pain, which was always associated with several other SFN symptoms of similarly high intensities. A pauci-symptomatic cluster comprised patients who experienced few SFN symptoms, generally of low to moderate intensity. The largest cluster was characterized by intense fatigue, myalgias and subjective weakness, but lower intensities of burning pain and paresthesia. This data-driven study introduces a new approach to subgrouping patients with SFN. Considering both neuropathic pain and pernicious symptoms beyond pain, we identified three clusters, which may be related to distinct pathophysiological mechanisms. Although additional validation will be required, our findings represent a step towards stratified treatment approaches and, ultimately, personalized treatment.

Association between COVID-19 exposure and autonomic nervous system dysfunction in apparently healthy adults: an observational study.

Coronavirus disease (COVID-19) is a respiratory disease caused by SARS-CoV-2, which complicates the functioning of multiple systems, including the autonomic nervous system (ANS), causing dysautonomia. Investigation of dysautonomia and its association with exposure to COVID-19 is limited in healthy people. Therefore, the study aimed to investigate the relationship between ANS dysautonomia and coronavirus exposure and compare the ANS function between exposed and non-exposed to COVID-19. The study involved 141 participants, with a mean age of 18-24.5 years, 83% male (49.6% exposed to COVID-19). The ANS was measured using a composite autonomic symptom scale (COMPASS-31) questionnaire and heart rate variability (HRV) using photoplethysmography. Exposure to COVID-19 was investigated using two national health-status tracking and COVID-19 exposure applications, "Sehhaty" and "Twakkalna". A significantly inverse weak correlation between COMPASS-31 scores and COVID-19 exposure (r=-0.2, p=0.04). No significant association was found between HRV and COVID-19 exposure. COMPASS-31 scores for the exposed group (median=15, n=70) were significantly higher than those for the non-exposed group (median=12, n=71), U=1,913.5, p=0.03. Height (r=-0.4, p=0.002) and gender (r=0.3, p=0.001) were moderately correlated with COMPASS-31 among the exposed group. These findings indicated that exposure to COVID-19 was associated with poorer ANS scores measured via COMPASS-31. Additionally, exposure to COVID-19 resulted in higher dysautonomia symptoms than non-exposed. Height and gender differences contribute to the severity of dysautonomia among exposed people.

Comparison of autonomic dysfunction in patients with Parkinson's Disease, progressive supranuclear palsy, and multiple system atrophy.

To assess and compare autonomic nervous system (ANS) dysfunction, especially cardiovascular dysautonomia, in Parkinson's Disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and healthy controls. Assessment of ANS can be useful in differential diagnosis. Dysautonomia affects quality of life and can lead to potentially life-threatening complications. There is very little literature data regarding dysautonomia in PSP in relation to other parkinsonian syndromes. This study expands the knowledge about ANS dysfunction in parkinsonisms, especially PSP. Patients with PD, MSA and PSP were prospectively recruited to our study. Demographic data and information about clinical and neuropsychological assessment, medication and comorbidities was collected. SCOPA-AUT questionnaire, 5-minute tilt test, and 5-minute heart rate variability (HRV) analysis in time and frequency domains were used to assess ANS. Analysis was also performed in patients with PSP-RS and PSP-P phenotypes, and in a subgroup with eliminated confounding factors, including age and disease duration. 76 PD, 25 PSP, and 12 MSA patients, and 20 controls, were included. Symptoms of dysautonomia revealed by a SCOPA-AUT questionnaire were present in all groups of patients. Urinary dysfunction was more pronounced in atypical parkinsonisms, and cardiovascular symptoms in α-synucleinopathies. HRV was disrupted in all groups of patients. However, when PSP-P and PSP-RS phenotypes were considered, HRV was diminished in PSP-RS, but there were no differences in HRV parameters between PSP-P and controls. Neurogenic orthostatic hypotension was present in 25% of PD and 58% of MSA patients, but it was absent in PSP patients and the control group. 13 PD and nine PSP patients and 16 controls were included in subanalysis. This revealed that PSP, but not PD, patients had significantly more symptoms of dysautonomia and lower HRV indices compared to controls, and that orthostatic hypotension was even more common in PD than in controls. Our study suggests that dysautonomia is common in PD, MSA and PSP, even though it has different profiles in the different diseases. NOH is present in PD and MSA, but not in PSP.

Clinical-Genomic Analysis of 1261 Patients with Ehlers-Danlos Syndrome Outlines an Articulo-Autonomic Gene Network (Entome).

Systematic evaluation of 80 history and 40 history findings diagnosed 1261 patients with Ehlers-Danlos syndrome (EDS) by direct or online interaction, and 60 key findings were selected for their relation to clinical mechanisms and/or management. Genomic testing results in 566 of these patients supported EDS relevance by their differences from those in 82 developmental disability patients and by their association with general rather than type-specific EDS findings. The 437 nuclear and 79 mitochondrial DNA changes included 71 impacting joint matrix (49 COL5), 39 bone (30 COL1/2/9/11), 22 vessel (12 COL3/8VWF), 43 vessel-heart (17FBN1/11TGFB/BR), 59 muscle (28 COL6/12), 56 neural (16 SCN9A/10A/11A), and 74 autonomic (13 POLG/25porphyria related). These genes were distributed over all chromosomes but the Y, a network analogized to an 'entome' where DNA change disrupts truncal mechanisms (skin constraint, neuromuscular support, joint vessel flexibility) and produces a mirroring cascade of articular and autonomic symptoms. The implied sequences of genes from nodal proteins to hypermobility to branching tissue laxity or dysautonomia symptoms would be ideal for large language/artificial intelligence analyses.

Symptoms of dysautonomia and REM sleep behavior disorder in patients with narcolepsy

Symptoms of dysautonomia and REM sleep behavior disorder in patients with narcolepsy

Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

To investigate the etiology of cerebellar ataxia in an adult male patient. We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities. The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms. Nerve conduction studies showed mild peripheral sensory neuropathy and normal motor nerve conduction velocities. Brain imaging showed progressive cerebellar atrophy and gliosis of the olivopontocerebellar fibers, characterized by T2 hyperintensity within the pons. Genetic testing revealed a likely pathogenic germline variant in MFN2 (NM_014874: c.[838C>T];[=], p.(R280C)) in the GTPase domain (G) interface; pathogenic variants of MFN2 typically cause hereditary sensory and motor neuropathy VI or Charcot-Marie-Tooth disease 2A. The presence of progressive ataxia, "hot cross bun" sign, and dysautonomia has been associated with multiple system atrophy, cerebellar type (MSA-C). We describe progressive cerebellar ataxia in an individual with a deleterious variant in MFN2. Our findings suggest that pathogenic variants in MFN2 can result in a spectrum of phenotypes including cerebellar ataxia with cerebellar-pontine atrophy in the absence of significant neuropathy and in a manner closely resembling MSA-C.

HEART Rate Variability Biofeedback for LOng COVID Dysautonomia (HEARTLOC): Results of a Feasibility Study.

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. 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. 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. 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.

Anxiety and dysautonomia symptoms in patients with a NaV1.7 mutation and the potential benefits of low-dose short-acting guanfacine.

Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1mg/day facilitated symptom relief in two families with multiple members presenting withsevere generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms.

Quantification of Dysautonomia in Major Depressive Disorder Using the Composite Autonomic Scoring Scale-31 (COMPASS-31).

Background Dysautonomia denotes an alteration in the autonomic nervous system that can significantly lead to multiorgan failure. Conversely, depression not only affects cognitive functions but also poses a risk factor for sudden cardiac death. In our study, the Composite Autonomic Scoring-31 (COMPASS-31) is used to quantify the autonomic symptoms present if any in patients with depression. Materials and methods Forty-two patients with major depressive disorder (MDD) were recruited using a PHQ-9 questionnaire followed by a COMPASS-31 scale to quantify dysautonomia symptoms, and they were compared with healthy controls. Further regression analysis was conducted to establish any relationship between independent variables and COMPASS-31 scores. Results The average COMPASS-31 score in patients with MDD was 22.56±8.42, which was significantly increased compared to healthy controls (p=0.001).Furthermore, the differences persisted across various subdomains of the COMPASS-31 scale relative to severity of depression. Conclusion The study observations could provide a relevant perception regarding the association between depressionand autonomic dysfunction with the use of a simple and brief yet validated instrument COMPASS-31, which can be utilized for screening at the primary care level.

SAT153 A Case Of Hypoglycemia-induced Chest Pain Secondary To Adult Nesidioblastosis: A Case Report

Abstract Disclosure: O.L. Medina Espitia: None. A. Quintero Altare: None. V.A. Clavijo: None. L.C. Martínez Delgado: None. The report of the present case in the medical literature is important in itself because of the infrequency of Nesidioblastosis. Additionally, it allows us to show unusual forms of presentation such as chest pain, and dynamic electrocardiographic changes in the ST segment with negative troponin, which coincide with episodes of hypoglycemia. At admission, the patient consulted the emergency department for a clinical presentation consisting of progressive retrosternal chest pain radiating to the left cervical region associated with dyspnea for medium exertion, palpitations, and dysautonomic symptoms, given by nausea. Due to episodes of chest pain, a coronary arteriography had been performed six months before admission without evidence of obstructive lesions. During hospitalization, episodes of hypoglycemia were observed. Remarkably, it was possible to document Dynamic ST changes in all EKG leads during episodes of hypoglycemia, as shown in Figure 1. Among the differential diagnoses, hypoglycemia secondary to adrenal or thyroid dysfunction was considered a first possibility, which was ruled out in the presence of normal paraclinical tests and medications that could generate hypoglycemia (negative sulfonylurea tests) were ruled out. A fasting test was performed with results showing endogenous hyperinsulinemic hyperinsulinemia with levels of insulin in 35.5 mg/dL, C-peptide 9.34 ng/dL and blood glucose 34 mm/dL. MRI of the abdomen without lesions. Due to a history of gastric bypass, endoscopic ultrasonography was not performed, therefore pancreatic calcium stimulation test was performed with evidence of a significant delta over the territory of the splenic artery. A distal pancreatectomy was obtained. Pathology report with findings suggestive of Nesidioblastosis (Figure 2.). There was a complete resolution of episodes of hypoglycemia and chest pain for two weeks. The recurrence of hypoglycemia episodes led to ambulatory treatment, with diazoxide with complete resolution of events. Presentation: Saturday, June 17, 2023

Paraneoplastic Neurologic Syndrome in Small Cell Lung Carcinoma

A 54-year-old male smoker, previously in good health, was admitted to the hospital due to a tingling sensation in his upper and lower extremities. He reported difficulty walking due to a loss of balance and numbness, leading to an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. Brain and spine magnetic resonance imaging, along with needle electromyography, yielded inconclusive findings. However, a nerve conduction study indicated a length-dependent pattern of sensory-dominant polyneuropathy. A cerebrospinal fluid study did not reveal any specific findings in terms of cell numbers, proteins, or immune tests. Following hospitalization, the patient reported progressive dizziness upon standing, leading to a preliminary diagnosis of orthostatic hypotension. However, a positive anti-Hu autoantibody test, along with chest computed tomography and positron emission tomography scans, revealed a mass in the left interlobar lymph node, suggestive of lung cancer. An endoscopic biopsy confirmed the presence of small cell lung cancer (SCLC). The patient underwent chemo-radiation treatment for the SCLC and immunoglobulin therapy for sensory ganglionopathy. As a result, a definitive diagnosis of paraneoplastic neurologic syndrome was made. Although such cases are rare, our observations suggest that symptoms of dysautonomia and sensory ganglionopathy may be associated with the production of anti-Hu antibodies.

Idiopathic cervical dystonia and non-motor symptoms: a pilot case-control study on autonomic nervous system

PurposeNon-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature.MethodsWe conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio.ResultsICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing.ConclusionICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations.

Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients

Several disabling symptoms potentially related to dysautonomia have been reported in “long-COVID” patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31–43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0–16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

PO-03-220 IMPACT OF COVID-19 INFECTION ON BASELINE AUTONOMIC SYMPTOMS IN PATIENTS WITH PRE-EXISTING POSTURAL TACHYCARDIA SYNDROME AND ORTHOSTATIC INTOLERANCE

Recently there have been several published case series of some survivors of COVID-19 infection left with chronic symptoms of autonomic dysfunction (AD) with features of orthostatic tachycardia syndrome (POTS). However, the impact of this viral illness on the underlying autonomic symptoms has not been studied in the patient population who have a pre-existing POTS diagnosis and are receiving treatment. So far, the impact of this viral illness on the underlying autonomic symptoms has not been studied in patients with a pre-existing POTS diagnosis and receiving treatment. Our study aims to report the impact of a COVID-19 infection on these patient populations, both during the acute phase of the disease and post-recovery. Our Institution Review Board (IRB) approval was obtained to access charts of the study subjects. Basic demographic and diagnosis details including the age, sex, prominent symptoms, duration of POTS diagnosis, medications, associated autonomic disease, and medication regimen were obtained from the retrospective chart review. Additional information regarding COVID-19 infection, course of illness, need for hospitalization, worsening of POTS symptoms, need for ED visits, improvement with the escalation of therapy, the type of persisting symptoms, and vaccination status were obtained from both chart review and details from the patients during the scheduled office visit. A total of 49 patients were studied. About 42 patients (82 %) had the alpha-variant infection before the vaccines were available. 28% (14 patients) of them had tested positive for infection more than once (i.e infection with alpha, delta, or omicron variant). About 38 (92.7%) of them reported having worsening of their baseline POTS symptoms during the active infection phase. About 28 patients (57 %) experienced worsening of their dysautonomia symptoms for at least 1-6 months post-infection. Nearly 30 patients (73.2%) required additional therapy for their symptom control and improvement. Of subjects with pre-existing POTS, most experienced a worsening of their baseline autonomic symptoms after suffering the COVID-19 infection which required additional pharmacotherapy for their symptom improvement. The majority of them had recovered within 6 months of therapy. From our observation, it is evident that the COVID-19 infection exacerbates the underlying symptoms in patients with established POTS disease.

Dysautonomia symptoms and quality of life in non-hospitalized neurology outpatients with post-acute sequelae of COVID-19 (P8-9.005)

Dysautonomia symptoms and quality of life in non-hospitalized neurology outpatients with post-acute sequelae of COVID-19 (P8-9.005)

Rare Case of DPPX Encephalitis (P4-5.007)

<h3>Objective:</h3> N/A <h3>Background:</h3> Dipeptidyl-peptidase–like protein 6 (DPPX) antibody–associated encephalitis is a rare syndrome that includes weight loss, painful gastrointestinal symptoms, cognitive dysfunction, and CNS hyperexcitability. We describe a case of anti-DPPX encephalitis in a patient with painful GI symptoms and cognitive decline who underwent an extensive evaluation prior to diagnosis and treatment. <h3>Design/Methods:</h3> A 53 year old male presenting with recurrent emergency room visits with multiple seemingly unrelated symptoms. Symptoms occurred following a cruise and included skin discoloration, myalgias, and dyspnea. Respiratory symptoms resolved with standard bronchospastic treatment. He later developed dysesthesias, abdominal discomfort, and sixty pound weight loss. An extensive gastrointestinal evaluation was unremarkable. Persisting symptoms included anxiety and cognitive decline including apathy, memory impairment, and a persistent child-like demeanor, as well as exaggerated startle response. He underwent an inpatient psychiatric stay. His anxiety and depression slightly improved with psychotropic medications, however he did not return to his baseline positive demeanor. Symptoms of dysautonomia included episodic flushing and diaphoresis. Staring spells and unintelligible speech did not correlate with any simultaneous EEG recording. CSF resulted normal cell count and minimal increased protein (65 mg/dL). A lack of specific diagnosis and progressive decline prompted serum autoimmune antibody testing. Surprisingly, a positive anti-DPPX titer of 1:61440 was detected. Referred to oncology, the patient was treated sequentially with plasmapheresis and steroids, rituximab, and mycophenylate mofetil with a slight improvement in mental status over a period of weeks. <h3>Results:</h3> N/A <h3>Conclusions:</h3> Dipeptidyl-peptidase–like protein 6 (DPPX) is expressed in the hippocampus, cerebellum, striatum, and myenteric plexus, resulting in the unique presentation of DPPX antibody–associated encephalitis. This syndrome should be considered in patients with a triad of gastrointestinal symptoms, cognitive decline, and evidence of CNS hyperexcitability. Practitioners caring for patients with unknown CNS syndromes should have a low threshold for ordering CSF and serum CNS encephalitis panels, prompting earlier diagnosis. <b>Disclosure:</b> Dr. Pawate has nothing to disclose. Dr. Sandhu has nothing to disclose. Dr. Weisman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Small has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.

Disautonomía gastrointestinal como manifestación de mielitis transversa: Reporte de caso

Inflammatory transverse myelitis is a rare condition that affects one or more levels of the spinal cord. Its etiology includes multiple sclerosis, infectious causes, or disorders within the spectrum of neuromyelitis optica. It presents acutely with motor, sensory, and/or dysautonomic symptoms, such as those related to the gastrointestinal and urinary systems. Diagnosis is based on symptomatology, evolution, and is confirmed by lumbar puncture, magnetic resonance imaging, and complete blood analysis. We present a clinical case of a patient with transverse myelitis who presented with gastrointestinal symptoms, motor symptoms, and was diagnosed with magnetic resonance imaging.

Polineuropatías

Polyneuropathies are defined by the generalized involvement and dysfunction of the peripheral nervous system, generating combinations of symptoms such as hypoesthesia, dysesthesia, or weakness that usually starts in the distal regions of the limbs as well as dysautonomia symptoms such as orthostatism and gastroparesis. The peripheral nerve consists of highly specialized, very long nerve cells. These factors make it especially vulnerable to a variety of metabolic, infectious, toxic, autoimmune, and even paraneoplastic factors, which may affect its function and structure. Therefore, the mechanisms that lead to the onset of polyneuropathy and its symptoms are heterogeneous. The diagnostic process for polyneuropathies should include all of these diverse possibilities. Therefore, in addition to a detailed case history and neurological and physical examination, it is often necessary to combine multiple sophisticated analytical determinations, neurophysiological studies, cerebrospinal fluid studies, and even a peripheral nerve biopsy in order to determine the final etiology. Despite this, the rate of idiopathic polyneuropathy is often high. Specific treatment, when possible, as well as the prognosis depend in large part on the underlying cause. However, the treatment of symptoms such as neuropathic pain or dysautonomia are common in most polyneuropathies.