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Respiratory Medicine Aug 2018Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and... (Review)
Review
BACKGROUND
Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia.
METHODS
We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
RESULTS
Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy.
CONCLUSIONS
Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
Topics: Bronchoalveolar Lavage; Bronchoscopy; Brugada Syndrome; Consensus; Deglutition Disorders; Dysautonomia, Familial; Evidence-Based Practice; Humans; New York; Pneumonia, Aspiration; Polysomnography; Prospective Studies; Respiration Disorders; Respiratory Function Tests
PubMed: 30053970
DOI: 10.1016/j.rmed.2018.06.017 -
Journal of the American Academy of... Feb 2024To systematically investigate if there is a significant association between markers of autonomic functioning and emotional dysregulation (ED) in children and adolescents. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically investigate if there is a significant association between markers of autonomic functioning and emotional dysregulation (ED) in children and adolescents.
METHOD
Based on a preregistered protocol (PROSPERO: CRD42021239635), PubMed, Web of Knowledge/Science, Ovid MEDLINE, Embase, and APA PsycInfo databases were searched until April 21, 2021, to identify empirical studies reporting indices of autonomic nervous system (ANS) functioning in youths meeting DSM (version III, IV, IV-TR, 5 or 5-TR) or International Classification of Diseases (ICD) (version 9 or 10) criteria for any psychopathological/neurodevelopmental condition and assessed for ED with a validated scale. Eligible outcomes included correlation coefficients between ED and ANS measures or differences in ANS measures between youths with and without ED. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random-effects meta-analyses were used for data synthesis.
RESULTS
There were 12 studies (1,016 participants) included in the descriptive review and 9 studies (567 participants) included in the meta-analyses. No evidence of a significant association between ED and altered cardiac or electrodermal functioning was found. However, exploratory meta-regressions suggested a possible association between reduced resting-state cardiac vagal control and increased ED.
CONCLUSION
This study did not find evidence of an association between ED and autonomic dysfunction. However, preliminary evidence that reduced vagal control at rest might be a transdiagnostic marker of ED in young people was found. Additional studies comparing autonomic measures in youths with and without ED are needed and should also assess the effects of interventions for ED on ANS functioning.
STUDY PREREGISTRATION INFORMATION
Systematic Review and Meta-Analysis: Is Autonomic Nervous System Functioning Atypical in Children and Adolescents With Emotional Dysregulation? https://www.crd.york.ac.uk/prospero/; CRD42021239635.
Topics: Adolescent; Child; Humans; Cohort Studies; Cross-Sectional Studies; Neurodevelopmental Disorders
PubMed: 36841327
DOI: 10.1016/j.jaac.2023.01.017 -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203 -
Medicina (Kaunas, Lithuania) Apr 2023: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without... (Review)
Review
: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). : A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. : Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. : In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.
Topics: Humans; Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Hyperemia; Randomized Controlled Trials as Topic; Non-Randomized Controlled Trials as Topic
PubMed: 37109728
DOI: 10.3390/medicina59040770 -
The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2 -
Neurology Jul 2021To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at...
OBJECTIVE
To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester.
METHODS
We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests).
RESULTS
A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group ( < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period.
CONCLUSIONS
ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.
Topics: Afferent Pathways; Autonomic Nervous System Diseases; Baroreflex; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Retrospective Studies
PubMed: 33947784
DOI: 10.1212/WNL.0000000000012149 -
Clinical Cardiology Jul 2023Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitamin D-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.
Topics: Humans; Tilt-Table Test; Syncope, Vasovagal; Syncope; Vitamin D Deficiency; Vitamin D
PubMed: 37226313
DOI: 10.1002/clc.24035 -
International Journal of Environmental... Mar 2022Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV.... (Meta-Analysis)
Meta-Analysis Review
Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV. Design: A systematic review and meta-analysis on the impact of hyperthyroidism on HRV. Methods: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hyperthyroidism and healthy controls. Random-effects meta-analysis was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals (or Normal-to-Normal intervals—NN), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. Results: We included 22 studies with 10,811 patients: 1002 with hyperthyroidism and 9809 healthy controls. There was a decrease in RR (effect size = −4.63, 95% CI −5.7 to −3.56), SDNN (−6.07, −7.42 to −4.71), RMSSD (−1.52, −2.18 to −0.87), pNN50 (−1.36, −1.83 to −0.88), TP (−2.05, −2.87 to −1.24), HFnu (−3.51, −4.76 to −2.26), and VLF power (−2.65, −3.74 to −1.55), and an increase in LFnu (2.66, 1.55 to 3.78) and LF/HF ratio (1.75, 1.02 to 2.48) (p < 0.01). Most parameters had ES that was twice as high in overt compared to subclinical hyperthyroidism. Increased peripheral thyroid hormones and decreased TSH levels were associated with lower RR intervals. Conclusions: Hyperthyroidism is associated with a decreased HRV, which may be explained by the deleterious effect of thyroid hormones and TSH. The increased sympathetic and decreased parasympathetic activity may have clinical implications.
Topics: Cardiovascular System; Heart; Heart Rate; Humans; Hyperthyroidism; Thyrotropin
PubMed: 35329294
DOI: 10.3390/ijerph19063606 -
Clinical Autonomic Research : Official... Sep 2019Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic...
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.
Topics: Amyloid Neuropathies, Familial; Autonomic Nervous System Diseases; Humans
PubMed: 31473866
DOI: 10.1007/s10286-019-00630-y -
Journal of Diabetes and Its... Nov 2021To estimate the prevalence of neuropathy in adolescents with type 1 diabetes. (Review)
Review
AIMS
To estimate the prevalence of neuropathy in adolescents with type 1 diabetes.
METHODS
Systematic collection of published studies exploring the prevalence of large fibre neuropathy (LFN), small fibre neuropathy (SFN), and autonomic neuropathy in adolescents with type 1 diabetes. Following prospective registration (Prospero CRD42020206093), PubMed, EMBASE, and Cochrane Library were searched for studies from 2000 to 2020. PICO framework was used in the selection process (Population: adolescents aged 10-19 years with type 1 diabetes; Intervention: diagnostic methods for neuropathy; Comparison: reference data; Outcome: data on prevalence or comparison). Data were extracted concerning study quality based on available data and established methods for determining and diagnosing various neuropathy types.
RESULTS
From 2,017 initial citations, 27 studies (7589 participants) fulfilled eligibility criteria. The study population (47% males) had a diabetes duration between 4.0 and 10.6 years, and HbA1c level between 7.3 and 10.8%, 56-95 mmol/mol. The prevalence of LFN, based on nerve conduction studies, was 10-57%. Based on other tests for neuropathy, the prevalence of LFN and SFN was 12-62%, and that of cardiac autonomic neuropathy was 12-75%.
CONCLUSION
The described prevalence of neuropathy in adolescents with type 1 diabetes varied, which can be methodological due to different screening methods and classifications of neuropathy.
Topics: Adolescent; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Male; Peripheral Nervous System Diseases; Prevalence; Prospective Studies
PubMed: 34429229
DOI: 10.1016/j.jdiacomp.2021.108027