Clinical-epidemiological characterization of patients with long COVID in Mexico.

BACKGROUND: Long COVID is defined as the persistence of COVID-19 symptoms four weeks after having undergone acute infection, according to the most recent CDC definition. It is estimated that there are 65 million people affected by this entity, although other figures speak of 200 million. OBJECTIVE: To characterize the population affected by long COVID in Mexico. MATERIAL AND METHODS: Patients older than 18 years who agreed to answer an online survey and who met the criteria for long COVID were included. RESULTS: Data from 203 subjects were included, with 138 (68.0%) being found to be females, and average age to be 41.8 years; 29.6% had severe disease, and 70.4%, mild to moderate disease; 89.7% had received prior COVID-19 vaccination: 6.9% had received one dose; 31.5%, two doses; and 51.2%, three or more doses. The main risk factors were diabetes, overweight or obesity, and hypertension. The most commonly reported symptom was fatigue, followed by other neuropsychiatric manifestations. CONCLUSION: It is important for the population affected by long COVID to be characterized in order to generate diagnostic and treatment protocols.

ANTECEDENTES: El COVID persistente se define como la persistencia de síntomas de COVID-19 después de cuatro semanas de cursar con un cuadro agudo, según la definición más reciente de los Centers for Disease Control and Prevention. Se estima que existen 65 millones de personas afectadas por esta entidad, aunque algunos reportes indican 200 millones. OBJETIVO: Caracterizar a la población afectada por COVID persistente en México. MATERIAL Y MÉTODOS: Se incluyeron pacientes mayores de 18 años que consintieron responder a una encuesta en línea y que cumplían los criterios de COVID persistente. RESULTADOS: Se incluyeron los datos de 203 sujetos. Se identificó que 138 (68.0 %) contestaron ser del sexo femenino, con una media de edad de 41.8 años; 29.6 % presentó enfermedad grave y 70.4 %, enfermedad leve a moderada; 89.7 % había recibido vacunas previas para COVID-19: 6.9 %, una dosis; 31.5 %, dos dosis; y 51.2 %, tres o más dosis. Los principales factores de riesgo fueron diabetes, sobrepeso u obesidad e hipertensión arterial sistémica. El principal síntoma reportado fue fatiga, seguido de otras manifestaciones neuropsiquiátricas. CONCLUSIÓN: Es importante caracterizar a la población para generar protocolos de diagnóstico y tratamiento.

Moderately intense physical exercise alleviates electrocardiographic changes induced by cisplatin in rats.

INTRODUCTION AND OBJECTIVE: Cisplatin induces many collateral effects such as gastrointestinal disorders, nephrotoxicity, and dysautonomia. Recently our group showed that cisplatin treatment induces gastric emptying delay and that physical exercise and treatment with pyridostigmine prevent this change. In the current study, we investigated the role of moderate exercise on cardiac activity and autonomic balance in rats treated with cisplatin. METHODS: Male Wistar rats were divided into saline, cisplatin, exercise, and exercise+cisplatin groups. Cardiac and autonomic disorders were induced by (cisplatin - 3 mg/kg, i.p. once a week/per 5 weeks). Exercise consists of swimming (1 hour per day/5× day per week/per 5 weeks without overload). Forty-eight hours after the last session of the training or treatment, we assessed the cardiac activity and HRV via electrocardiogram analysis in DII derivation. RESULTS: Cisplatin increase (p<0.05) R-R' interval and decrease (p<0.05) heart rate vs. saline. Exercise+cisplatin prevented (p<0.05) changes in R-R' interval. Exercise per se induced bradycardia vs. saline group. We observed an increase in LF (nu) and a decrease in HF (nu) in the cisplatin group vs. saline. These changes were not significant. Moreover, cisplatin treatment increased (p<0.05) QT, QTc, and JT intervals compared with the saline group. In the exercise+cisplatin groups these increases were prevented significantly (p<0.05). CONCLUSION: In the current study, chronic use of cisplatin induced electrocardiographic changes without altering autonomic balance. Moderate physical exercise prevented this phenomenon indicating that exercise can be beneficial in patients in chemotherapy.

Vagal dysautonomia in patients with Chagas disease and mortality: 14-year results of a population cohort of the elderly.

INTRODUCTION: Great part of Chagas disease (ChD) mortality occurs due to ventricular arrhythmias, and autonomic function (AF) may predict unfavorable outcomes. We aimed to evaluate the predictive value of AF indexes in ChD patients. METHODS: The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. AF was assessed by the maximum expiration on minimum inspiration (E:I) ratio during ECG acquisition and by heart rate variability indices: SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)), calculated using a computer algorithm. Cox proportional hazards regression was performed to access the prognostic value of AF indexes, expressed as terciles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. RESULTS: From 1742 qualifying residents, 1000 had valid AF tests, being 321 with ChD. Among these, median age was 68 (64-74) years, and 32.5% were men. In Cox survival analyses, only SDRR was associated with all-cause mortality in non-adjusted models: SDRR (hazard ratio (HR): 1.26 (95% CI 1.08-1.47), p < 0.001), E:I ratio (HR: 1.13 (95% CI 0,98-1.31), p = 0.10) and RMSSD (HR: 0.99 (0.86-1.16), p = 0.95). After adjustment for sex and age, none of the indexes remained as independent predictors. CONCLUSION: Among elderly patients with ChD, AF indexes available in this cohort were not independent predictors of 14-year mortality.

Autonomic function in sporadic and familial ALS type 8.

OBJECTIVE: To characterize and compare autonomic function in patients with sporadic (sALS) and familial ALS type 8 (fALS8). METHODS: We selected 11 patients with sALS (7 men), 14 with fALS8 (8 men) and 26 controls (15 men). All groups were gender and age-matched. For each subject, Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) was applied and data from heart rate variability, Quantitative Sudomotor Axon Reflex Test (QSART) and skin sympathetic response (SSR) were collected. These data were compared across groups using nonparametric tests. P-values < 0.05 were considered significant. RESULTS: SCOPA-AUT revealed predominant clinical complaints in thermoregulatory, pupillomotor and sexual domains in fALS8 relative to sALS as well as controls. Neurophysiological tests demonstrated significant differences in Valsalva ratio, Expiratory:Inspiratory index and RR minimum values in both ALS groups relative to controls. Sudomotor dysfunction was also observed in sALS and fALS8 groups, as shown by reduced medial forearm and foot QSART volumes and absence of SSR in lower limbs. CONCLUSIONS: Dysautonomia - cardiac and sudomotor - is part of the phenotype in sALS and fALS8. The profile of autonomic symptoms, however, is different in each group. SIGNIFICANCE: Patients with fALS8 and sALS have autonomic dysfunction involving both sympathetic and parasympathetic divisions.

Electrophysiological assessment of peripheral and central autonomic disorders.

The autonomic nervous system (ANS) coordinates multiple reflex actions which are essential for life. The tests employed to evaluate the ANS provide valuable information of the functional state of these reflex arcs. The ideal test should be simple to perform, noninvasive, reproducible, sensitive, specific, safe, and appropriate for longitudinal studies. The availability of computer-based techniques has facilitated the electrophysiological assessment of ANS-mediated reflexes. The information provided by autonomic testing must be analyzed in combination with the clinical history and physical examination of the patient, allowing for a hypothesis that can be tested. Properly performed and interpreted, ANS testing can be used to confirm the presence of an ANS disturbance and the involved functional pathways, as well as the extent, intensity, and site of injury. This chapter describes the most important electrophysiological tests used to evaluate the ANS control of cardiovascular reflexes and sweat gland activity.

The Relationship between Paresthesia and the Presence of Cardiac Dysautonomia in Patients with Post-COVID-19 Syndrome: A Preliminary Observational Study.

INTRODUCTION: Post-Coronavirus disease 2019 (Post-COVID-19) syndrome has neurological symptoms related to the dysfunction of the autonomous nerve system. However, a pathogenic relationship between post-COVID-19 syndrome and dysautonomia still remains to be demonstrated. Establishing a pathogenic relationship between paresthesia and the presence of cardiac dysautonomia in patients with post-COVID-19 syndrome is the objective of this study. PARTICIPANTS AND METHODS: This observational study was carried out in the neurophysiology service wing of the Juan Bruno Zayas Hospital, Santiago de Cuba, in Cuba. The patients were recruited through a post-COVID-19 clinic at the same hospital. A variability study of cardiac frequency and a test of autonomic cardiovascular reflexes was carried out, which is composed of deep breathing, orthostatism, and the Valsalva maneuver. RESULTS: The variability parameters of the cardiac frequency, the expiration-inspiration ratio between deep breaths, and the Valsalva Index showed no statistically significant differences between healthy participants and those with post-COVID-19 syndrome. During the Valsalva maneuver, there was a greater cardiac frequency response in participants with post-COVID-19 syndrome than in healthy subjects. The difference in supine and standing blood pressure was significantly minor in patients with post-COVID-19 syndrome. The logarithm of high frequency (log HF) increased significantly in patients with paresthesia when compared to patients without paresthesia. CONCLUSIONS: In the autonomic function tests, no signs of dysautonomia were found in patients with post-COVID-19 syndrome. The presence of paresthesias is associated with differences in cardiac vagal activity, which may suggest that damage to peripheral sensory nerve fibers could be associated with an affectation to autonomic fibres.

Disautonomía gastrointestinal como manifestación de mielitis transversa: Reporte de caso

La mielitis transversa, de origen inflamatorio, es una afectación rara de la médula espinal que afecta a uno o varios niveles. La etiología incluye esclerosis múltiple, causas infecciosas o trastornos del espectro de la neuromielitis óptica. Se presenta de forma aguda, con síntomas motores, sensoriales y/o disautonómicos como los gastrointestinales y urinarios. El diagnóstico se basa en la sintomatología, evolución y se confirma por punción lumbar, resonancia magnética nuclear y analítica sanguínea completa. Se presenta el caso clínico de una paciente con mielitis transversa, que debutó con sintomatología gastrointestinal, síntomas motores y confirmación diagnóstica con resonancia magnética nuclear.

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.

Centralized nociplastic pain causing fibromyalgia: an emperor with no cloths?

The leading school of thought views fibromyalgia as a central sensitization syndrome. Nociplastic pain is the recently proposed term to mechanistically explain central sensitization. Accumulating research suggests an alternate explanation; fibromyalgia can be conceptualized as a neuropathic pain syndrome and dorsal root ganglia (not the brain) as the primary fibromyalgia pain source. There is no need to propose nociplastic pain as new chronic pain mechanism.

Dysautonomia in RFC1-related disorder: Clinical and neurophysiological evaluation.

OBJECTIVE: To characterize and quantify autonomic involvement in patients with RFC1-related disorder of adult-onset cerebellar ataxia and idiopathic sensory neuropathy. METHODS: We enrolled 16 subjects with biallelic RFC1 (AAGGG)n expansions and 16 age and sex-matched healthy controls that underwent comprehensive clinical and neurophysiological evaluation. Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction (SCOPA-AUT) score was used to assess autonomic symptoms. Electrophysiological testing included assessment of heart rate variability and quantitative sudomotor axon reflex test (QSART). Between-group comparisons were assessed using non-parametric tests. RESULTS: In the patient group, there were 9 men/7 women and the median age was 60.5 years. SCOPA-AUT scores were significantly higher in the RFC1 group compared to controls (22 vs 10, p < 0.001). Half of patients had cardiac autonomic neuropathy. In neurophysiology, there was resting tachycardia combined with abnormal responses during Valsalva maneuver and deep breathing among patients. QSART responses were also significantly reduced in the RFC1 group, especially in the lower limbs. CONCLUSIONS: Autonomic dysfunction is frequent, clinically relevant and involves multiple domains in RFC1-related disorder. Patients have both sympathetic and parasympathetic involvement. From a topographical perspective, this condition is characterized by a small fiber autonomic axonopathy. SIGNIFICANCE: Dysautonomia is frequent, severe and related to peripheral damage in RFC1-related disorder.

Association between blood glucose levels and autonomic symptoms in Peru.

AIMS: To determine whether there is an association between high blood glucose levels and having autonomic symptoms among adults aged 30-69 years. MATERIAL AND METHODS: A population-based cross-sectional study was conducted. The presence of autonomic symptoms was defined as the positive response to any item of the Survey of Autonomic Symptoms (SAS). Blood glucose levels were defined as euglycemia, prediabetes, and type 2 diabetes (T2D), based on oral glucose tolerance test. Poisson regression, with link log and robust variance, and linear regression were conducted to evaluate the association of interest. RESULTS: A total of 1607 subjects, mean age 48.2 (SD: 10.6) and 810 (49.7 %) women, were included. T2D was associated with higher prevalence of erectile dysfunction (PR = 3.00; 95 % CI: 1.78-5.02) and dryness of mouth and eyes (PR = 1.29; 95 % CI: 1.02-1.61) compared with those with euglycemia. Those with T2D had 0.32 (95 % CI: 0.04-0.62) and 1.03 (95 % CI: 0.03-2.03) more points in the SAS score and severity scale, respectively. CONCLUSIONS: Erectile dysfunction and dry mouth and eyes are the more common autonomic symptoms associated with T2D. Our results suggest a periodic evaluation of sexual function and eye humidity among T2D patients.

Infarto de miocardio en un modelo murino de hiperactividad simpática cardíaca / Myocardial Infarction in a Murine Model of Cardiac Sympathetic Hyperactivity

RESUMEN Introducción: La disautonomía es uno de los mecanismos fisiopatológicos principales que marcan el pronóstico de la cardiopatía isquémica y la insuficiencia cardíaca. La búsqueda de nuevas oportunidades de tratamiento requiere un conocimiento más profundo de los efectos cardíacos de la activación simpática crónica. Objetivos: Estudiar el tamaño del infarto y la función ventricular izquierda en un modelo de ratones transgénicos con sobreexpresión de la proteína Gs-α cardíaca en el contexto de la isquemia/reperfusión miocárdica y el infarto crónico. Material y métodos: Ratones transgénicos (TG) con sobreexpresión cardíaca de la subunidad alfa de la proteína Gs y sus respectivos controles wild-type (WT) fueron sometidos a isquemia miocárdica regional de 30 minutos con 2 horas de reperfusión (IR) o un infarto sin reperfusión (I) de 28 días de evolución. Se cuantificó el tamaño del infarto (TI) con cloruro de 2,3,5-trifeniltetrazolio y se evaluó la función ventricular izquierda mediante ecocardiografía y estudio hemodinámico. Cada grupo experimental estuvo acompañado por un grupo control (WT / TG Sham-2hrs y WT / TG Sham-28d). Resultados: No hubo diferencias significativas en el TI luego de la IR entre los ratones TG y WT (57,3 ± 3,5% vs 59,2±2,5%, respectivamente, p = NS). La frecuencia cardíaca en los ratones TG fue mayor durante el desarrollo de todo el protocolo. Con la infarto se observó un descenso de la fracción de eyección (WT: Sham-28d: 82 ± 2,4% vs I-28d: 44 ± 4% y TG: Sham-28d 89 ± 2% vs I-28d 42 ± 3%; p <0,05) conjuntamente con una disminución de la fracción de acortamiento (FA), y los cambios del área fraccional (CAF) del ventrículo izquierdo (VI) en comparación con los valores basales y sus respectivos grupos controles. Sin embargo, no se observaron diferencias entre los grupos WT y TG. Conclusión: la sobreexpresión de la proteína Gs-α cardíaca no aumenta el tamaño del infarto ni modifica la función ventricular izquierda en la isquemia/reperfusión aguda y en el infarto crónico en comparación con sus respectivos controles

ABSTRACT Background: Dysautonomia is one of the main pathophysiological mechanisms that define the prognosis of ischemic heart disease and heart failure. The search for new treatment opportunities requires a deeper understanding of the cardiac effects of chronic sympathetic activation. Objective: The aim of this study was to analyze left ventricular infarct size and ventricular function in a transgenic mouse model with overexpression of the cardiac Gs-α protein, in the context of myocardial ischemia/reperfusion and chronic infarction. Methods: Transgenic mice (TG) overexpressing cardiac Gs-α and its wild-type variant (WT) were subjected to 30-minute regional myocardial ischemia followed by 2-hour reperfusion (IR) or non- reperfusion (I) with a 28-day follow-up period. Infarct size (IS) was quantified using 2,3,5-triphenyltetrazolium chloride and left ventricular function was evaluated by echocardiography and LV catheterization. Each experimental group was accompanied by a control group (WT/TG Sham-2hrs and WT/TG Sham-28d). Results: There were no significant differences in IS after IR between TG and WT mice (57.3 ± 3.5% vs. 59.2 ± 2.5%, respectively, p = NS). The heart rate in TG mice was higher throughout the experiment. With ischemia, a in ejection fraction (WT: Sham-28d: 82 ± 2.4% vs. I-28d: 44 ± 4% and TG: Sham-28d 89 ± 2% vs. I-28d 42 ± 3%; p <0.05) was observed together with a decrease in shortening fraction and left ventricular fractional area changes compared with baseline values and their respective control (Sham) groups. However, no differences were observed between the WT and TG groups. Conclusions: Cardiac Gs-α protein overexpression does not increase infarct size or modify left ventricular function in acute ischemia / reperfusion and chronic infarction compared with their respective controls.

Acute Hepatic Porphyria: Pathophysiological Basis of Neuromuscular Manifestations.

Acute hepatic porphyria represents a rare, underdiagnosed group of inherited metabolic disorders due to hereditary defects of heme group biosynthesis pathway. Most patients have their definite diagnosis after several years of complex and disabling clinical manifestations and commonly after life-threatening acute neurovisceral episodes or severe motor handicap. Many key studies in the last two decades have been performed and led to the discovery of novel possible diagnostic and prognostic biomarkers and to the development of new therapeutic purposes, including small interfering RNA-based therapy, specifically driven to inhibit selectively delta-aminolevulinic acid synthase production and decrease the recurrence number of severe acute presentation for most patients. Several distinct mechanisms have been identified to contribute to the several neuromuscular signs and symptoms. This review article aims to present the current knowledge regarding the main pathophysiological mechanisms involved with the acute and chronic presentation of acute hepatic porphyria and to highlight the relevance of such content for clinical practice and in decision making about therapeutic options.

Evaluación del disbalance autonómico en el paciente con serología positiva para enfermedad de Chagas: Score de diagnóstico y tratamiento

La enfermedad de Chagas es una enfermedad parasitaria (Trypanosoma cruzi), endémica en 21 países de América y que las migraciones la han dispersado en distintos continentes. Una de las manifestaciones más precoces de esta enfermedad son las alteraciones disautonómicas o disfunción autonómica. La severidad de este inadecuado funcionamiento del sistema nervioso autónomo resulta mensurable, de modo que la evolución y/o progresión de la enfermedad puede constatarse mediante la alteración de estudios clínicos y detección de anticuerpos antimuscarínicos. Estos anticuerpos están presentes en un 30% de los infectados y aparecen muy precozmente una vez instalada la parasitosis; además otros estudios, como la dispersión del QT (>65 mseg) y la variabilidad de la frecuencia cardíaca (<100 mseg) presentan valores anormales. La utilización de nuevos paradigmas de atención, diagnóstico y tratamientos adecuados son imprescindibles para prevenir el desarrollo de esta cardiopatía.

Chagas disease is a parasitic disease (Trypanosoma cruzi), endemic in 21 countries of America and that migrations have dispersed it in different continents. One of the earliest manifestations of this disease is dysautonomic alterations or autonomic dysfunction. The severity of this inadequate functioning of the autonomic nervous system is measurable, so that the evolution and/or progression of the disease can be verified by altering clinical studies and detecting antimuscarinic antibodies. These antibodies are present in 30% of those infected and appear very early once the parasitosis is installed; In addition, other studies, such as QT dispersion (> 65 ms) and heart rate variability (<100 ms) show abnormal values. The use of new paradigms of care, diagnosis and appropriate treatments are essential to prevent the development of this heart disease.

A doença de Chagas é uma doença parasitária (Trypanosoma cruzi), endêmica em 21 países da América e que as migrações a dispersaram em diferentes continentes. Uma das primeiras manifestações desta doença são as alterações disautonômicas ou disfunção autonômica. A gravidade desse funcionamento inadequado do sistema nervoso autônomo é mensurável, de modo que a evolução e/ou progressão da doença pode ser verificada alterando os estudos clínicos e detectando anticorpos antimuscarínicos. Esses anticorpos estão presentes em 30% dos infectados e aparecem muito cedo, uma vez instalada a parasitose; Além disso, outros estudos, como a dispersão do QT (> 65 mseg) e a variabilidade da freqüência cardíaca (<100 mseg), mostram valores anormais. A utilização de novos paradigmas de atendimento, diagnóstico e tratamentos adequados são essenciais para prevenir o desenvolvimento desta doença cardíaca.

Manifestaciones cardiovasculares de la enfermedad de Parkinson: revisión de la literatura / Cardiovascular manifestations of Parkinson's disease: literature review

RESUMEN La enfermedad de Parkinson es la segunda enfermedad neurodegenerativa más prevalente en el mundo, y sus manifestaciones cardinales son la bradicinesia, el temblor y la rigidez. Aunque ha sido considerado un trastorno motor, actualmente se considera como un trastorno neurológico complejo que afecta diferentes sistemas, por lo que genera manifestaciones motoras y no motoras variadas, además de manifestaciones autonómicas sistémicas. Las manifestaciones cardiovasculares en pacientes con enfermedad de Parkinson son frecuentes y, además, provocan un gran impacto sobre la calidad de vida. A continuación, se realiza una revisión narrativa de las principales manifestaciones cardiovasculares de la enfermedad de Parkinson, y de sus mecanismos fisiopatológicos.

SUMMARY Parkinson's disease is the second most prevalent neurodegenerative disease in the world and is characterized by bradykinesia, tremor, rigidity, and postural instability. Although it has been considered as a motor system disease, it is currently considered as a complex neurological disease with different motor, non-motor, and autonomic manifestations. Cardiovascular manifestations in patients with Parkinson's disease are frequent and they have a great impact on quality of life. This article seeks to carry out a narrative review of the pathophysiological mechanisms and the main cardiovascular clinical manifestations in patients with Parkinson's disease.

Minimum dose of levothyroxine restored the autonomic balance on a Dalmatian female dog with primary hypothyroidism

Background: Hypothyroidism is an endocrine disease that leads to a reduction in the hormones thyroxine (T3) and triiodothyronine (T4), which therapy with levothyroxine restores the clinical signs related to the metabolic rate. Due to the influence of thyroid hormones on the heart, which is under the constant influence of the autonomic nervous system (ANS), dogs with hypothyroidism can develop bradycardia, arrhythmia, and dysautonomia. Heart rate variability (HRV) assesses autonomic modulation by the Holter method, which is scarce in dogs. We aimed to report the cardiac and autonomic effects of the primary hypothyroidism untreated and treated with levothyroxine in a canine case by Holter monitoring. Case: A 7-year-old female Dalmatian, weighing 36 kg, was referred for clinical evaluation due to apathy, weight gain, low hair quality, and lethargy. On physical examination, alopecic lesions on the hind limbs and tail, as well as bradycardia with a heart rate (HR) of 40-50 beats per minute (bpm) were observed, in addition to a 3/6 mitral murmur and 2/6 tricuspid murmur. Given the suspicion of thyroid gland disorder, the blood hormonal measurement revealed an increase in thyroidstimulating hormone (TSH; 0.65 ng/mL) and a decrease in free T4 (0.11 ng/mL) and total T4 (0.44 ng/mL), confirming primary hypothyroidism. Therapy was started with a minimum dose of levothyroxine (0.913 mg, every 12 h), which clinical signs were restored in 5 months of treatment, with weight loss, hair growth, and active behavior. To assess the impact of untreated and treated hypothyroidism on the patients ANS, a Holter monitoring exam was performed for 24 h before and after therapy. Before treatment, the average HR was 75 bpm, and the HR<50 bpm occurred during 05 h 20 min 36 s. Still, 320 pause events (>2.0s), 1st-degree atrioventricular blocks (AVB), six...(AU)

State-of-the-art pharmacotherapy for autonomic dysfunction in Parkinson's disease.

Introduction: Autonomic dysfunction is one of the most frequent and disabling non-motor symptoms of Parkinson's disease (PD). It includes, among others, orthostatic hypotension (OH), sialorrhea, constipation, erectile dysfunction (ED), urinary dysfunction, and diaphoresis. They are usually under-recognized and suboptimally managed.Areas covered: Recommended treatments for dysautonomias are summarized with a description of the mechanism of action and observed results. The pathophysiology of each disorder is reviewed to pinpoint possible therapeutic targets. Drugs approved for treating dysautonomia in the general population along with those under development for PD-related dysautonomia are also reviewed. Finally, the key elements of each symptom that should be addressed in clinical trials' design are considered.Expert opinion: Midodrine, droxidopa, fludrocortisone, and domperidone may be used for OH treatment. Sialorrhea can be managed with botulin toxin injections and oral glycopyrrolate. Erectile dysfunction can benefit from sildenafil treatment, as urinary dysfunction can from solifenacin. Macrogol, lubiprostone, and probiotics might be effective in treating constipation. Further research is needed to determine adequate treatment for diaphoresis in PD patients. Multidisciplinary management of motor and non-motor symptoms in PD is the best approach for dysautonomias in PD.

Minimum dose of levothyroxine restored the autonomic balance on a Dalmatian female dog with primary hypothyroidism

Background: Hypothyroidism is an endocrine disease that leads to a reduction in the hormones thyroxine (T3) and triiodothyronine (T4), which therapy with levothyroxine restores the clinical signs related to the metabolic rate. Due to the influence of thyroid hormones on the heart, which is under the constant influence of the autonomic nervous system (ANS), dogs with hypothyroidism can develop bradycardia, arrhythmia, and dysautonomia. Heart rate variability (HRV) assesses autonomic modulation by the Holter method, which is scarce in dogs. We aimed to report the cardiac and autonomic effects of the primary hypothyroidism untreated and treated with levothyroxine in a canine case by Holter monitoring. Case: A 7-year-old female Dalmatian, weighing 36 kg, was referred for clinical evaluation due to apathy, weight gain, low hair quality, and lethargy. On physical examination, alopecic lesions on the hind limbs and tail, as well as bradycardia with a heart rate (HR) of 40-50 beats per minute (bpm) were observed, in addition to a 3/6 mitral murmur and 2/6 tricuspid murmur. Given the suspicion of thyroid gland disorder, the blood hormonal measurement revealed an increase in thyroidstimulating hormone (TSH; 0.65 ng/mL) and a decrease in free T4 (0.11 ng/mL) and total T4 (0.44 ng/mL), confirming primary hypothyroidism. Therapy was started with a minimum dose of levothyroxine (0.913 mg, every 12 h), which clinical signs were restored in 5 months of treatment, with weight loss, hair growth, and active behavior. To assess the impact of untreated and treated hypothyroidism on the patient’s ANS, a Holter monitoring exam was performed for 24 h before and after therapy. Before treatment, the average HR was 75 bpm, and the HR2.0s), 1st-degree atrioventricular blocks (AVB), six...

Prevalence and factors related to orthostatic syndromes in recently diagnosed, drug-naïve patients with Parkinson disease.

PURPOSE: The aim of this study was to explore the prevalence of and factors related to orthostatic syndromes in recently diagnosed drug-naïve patients with Parkinson disease (PD). METHODS: This was a cross-sectional study that included 217 drug-naïve patients with PD and 108 sex- and age-matched non-parkinsonian controls from the Parkinson's Progression Markers Initiative (PPMI) prospective cohort study who were devoid of diabetes, alcoholism, polyneuropathy, amyloidosis, and hypotension-inducing drugs. Orthostatic symptoms were evaluated using the Scales for Outcomes in PD-Autonomic Dysfunction (SCOPA-AUT). Ioflupane-I123 single-photon emission computerized tomography was used to evaluate striatal dopamine active transporter (DaT) levels. Blood pressure was assessed both in the supine position and 1-3 min after the switch to a standing position. Orthostatic hypotension (OH) was defined by international consensus, and orthostatic intolerance (OI) was defined as the presence of orthostatic symptoms in the absence of OH. RESULTS: Compared with non-parkinsonian controls, patients with PD experienced a mild fall in systolic blood pressure upon standing (p = 0.082). The prevalence of OH was 11.1% in PD patients and 5.6% in controls (p = 0.109). The prevalence of OI was higher in patients with PD than in controls (31.3 vs. 13.3%; p = 0.003). Logistic regression revealed that OH and OI were related to a lower striatal DaT level and higher SCOPA-AUT gastrointestinal score. CONCLUSIONS: Orthostatic syndromes were common in the recently diagnosed drug-naïve patients with PD enrolled in the study, but only the prevalence of OI was higher in PD patients than in the non-parkinsonian controls. Unlike motor or functional disability indicators, markers of dopaminergic striatal deficit and gastrointestinal dysfunction were associated with OH and OI.

Characteristics and natural history of autonomic involvement in hereditary ATTR amyloidosis: a systematic review.

BACKGROUND: Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis. METHODS: A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction. RESULTS: Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment. CONCLUSION: The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.

Disfunción autonómica en la enfermedad de Parkinson: enfoque práctico / Autonomic dysfunction in Parkinson's disease: A practical approach

RESUMEN Los síntomas por disfunción autonómica son comunes en la enfermedad de Parkinson y están presentes en todas las fases de la enfermedad. Cubren una amplia variedad de síntomas, como manifestaciones gastrointestinales, urinarias, disfunción eréctil e hipotensión ortostática, entre otros, lo que genera discapacidad y deterioro en la calidad de vida. Afortunadamente, con intervenciones no farmacológicas y farmacológicas estos síntomas pueden mejorar sustancialmente, por lo que su evaluación resulta vital para el bienestar del paciente.

SUMMARY Symptoms due to autonomic dysfunction are common in Parkinson's Disease, being present in all phases of the disease. It covers a wide variety of symptoms including gastrointestinal, urinary, erectile dysfunction, and orthostatic hypotension among others, generating disability and deterioration in quality of life. Fortunately, with non-pharmacological and pharmacological interventions, these symptoms can improve substantially, making the evaluation of these symptoms vital for the patient's well-being.