Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Basic Tests of Autonomic Function.

SUMMARY: Over the past 3 decades, tests of autonomic function have become increasingly standardized across most laboratories, particularly with commercially available equipment similar to other neurophysiologic tests. Most neurologically based laboratories perform four or five tests of autonomic function. Two of these, the sudomotor axon reflex response and the thermoregulatory sweat test (which some laboratories do not perform because it requires extensive equipment), examine sudomotor autonomic function. The remaining three, the cardiovascular response to a tilt table test, the cardiovascular response to the Valsalva maneuver, and the cardiac response to deep breathing examine cardiovascular autonomic function. Tests of sweating typically localize the lesion in the neuraxis, differentiating between central nervous system pathways, the spinal cord, or pre- or postganglionic roots or nerves. Tests of cardiovascular function delineate specific autonomic subsystem involvement, whether vagal parasympathetic as reflected in the deep breathing response and specific phases of the Valsalva maneuver or sympathetic adrenergic as reflected in the tilt table test and the other phases of the Valsalva. This review details the basic performance, analysis, and interpretation of these and a few other tests, with illustrative patient cases.

Pure autonomic failure.

In this chapter, we describe the history, presentation, diagnosis and treatment of pure autonomic failure (PAF). The pathology underlying this condition is thought to involve the deposition of alpha synuclein in the autonomic ganglia leading to diminished norepinephrine release and progressive autonomic dysfunction. We focus on various neurophysiological tests that may be used to evaluate the function of the peripheral autonomic nervous system including quantitative sudomotor axon reflex testing, thermoregulatory sweat testing, and others. These may help evaluate and diagnose various disorders of autonomic failure and neurogenic orthostatic hypotension including multiple system atrophy and Parkinson's disease dysautonomia. Management of PAF, including the therapeutic role of recent advances in pharmacologic treatment, is discussed.

Clinical neurophysiology of multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset, rapidly progressive neurodegenerative syndrome. The diagnosis of MSA is primarily clinical. Neurophysiologic studies can provide important clues to the diagnosis of MSA and differentiate it from other neurodegenerative diseases especially when the clinical picture is unclear. This chapter reviews common and less common neurophysiological studies useful in the diagnosis of MSA.

Autonomic neurophysiologic implications of disorders comorbid with bladder pain syndrome vs myofascial pelvic pain.

AIMS: The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences. METHODS: We compared the presence and relative time of onset of 27 other medical conditions in women with BPS, MPP, both syndromes, and healthy subjects. Analysis included an adjustment for multiple comparisons. RESULTS: Among 107 female subjects (BPS alone = 32; BPS with MPP = 36; MPP alone = 9; healthy controls = 30), comorbidities differentially associated with BPS included irritable bowel syndrome (IBS), dyspepsia, and chronic nausea, whereas those associated with MPP included migraine headache and dyspepsia, consistent with the distinct autonomic neurophysiologic signatures of the two disorders. PTSD (earliest), anxiety, depression, migraine headache, fibromyalgia, chronic fatigue, and IBS usually preceded BPS or MPP. PTSD and the presence of both pelvic pain disorders in the same subject correlated with significantly increased comorbid burden. CONCLUSIONS: Our study suggests a distinct pattern of comorbid conditions in women with BPS. These findings further support our hypothesis of primary vagal defect in BPS as compared with primary sympathetic defect in MPP, suggesting a new model for chronic these pelvic pain syndromes. Chronologically, PTSD, migraine, dysmenorrhea, and IBS occurred early, supporting a role for PTSD or its trigger in the pathophysiology of chronic pelvic pain.

Near-infrared spectroscopy muscle oximetry of patients with postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a disabling condition characterized by orthostatic intolerance with tachycardia in the absence of drop-in blood pressure. A custom-built near-infrared spectroscopy device (NIRS) is applied to monitor the muscle oxygenation, noninvasively in patients undergoing incremental head-up tilt table (HUT). Subjects (6 POTS patients and 6 healthy controls) underwent 30 mins of 70°on a HUT. The results showed a significant difference in deoxyhemoglobin (Hb), change-in-oxygenation (ΔOxy) and blood volume (ΔBV) between patients and healthy controls. However, oxyhemoglobin (HbO2) showed a significantly faster rate of change in the healthy controls during the first 10 mins of the tilt and during the recovery. This NIRS muscle oximetry tool provides quantitative measurements of blood oxygenation monitoring in diseases such as POTS.

Pediatric Disorders of Orthostatic Intolerance.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

Pediatric sleep and autonomic complaints.

OBJECTIVES: Little is known about the relationship between autonomic dysfunction and sleep disturbances. This study aimed to identify patterns of sleep disturbances and autonomic dysfunction in children. METHODS: A retrospective chart review of 14 children who underwent sleep and autonomic testing was performed. Subjects were divided into three groups based on sudomotor Composite Autonomic Severity Score Scale score and postural tachycardia syndrome criteria. Sleep quality, sleep architecture, and number of comorbidities were analyzed. RESULTS: There were no statistically significant differences between groups in measures of sleep quality, sleep architecture, and number of comorbidities. CONCLUSION: Patients with postural tachycardia syndrome and autonomic dysfunction experience multiple sleep-related complaints. The low power of our study did not allow firm conclusions, but there is no pattern to these abnormalities.

Comorbid Conditions Do Not Differ in Children and Young Adults with Functional Disorders with or without Postural Tachycardia Syndrome.

OBJECTIVE: To determine if several multisystem comorbid conditions occur more frequently in subjects with tilt-table defined postural tachycardia syndrome (POTS) compared with those without. STUDY DESIGN: Retrospective chart review of 67 subjects aged 6-24 years, referred to a tertiary care neurogastroenterology and autonomic disorders clinic for a constellation of functional gastrointestinal, chronic pain, and autonomic complaints. All patients underwent formal autonomic testing, Beighton scores assessment for joint hypermobility (0-9), and fibromyalgia tender points (0-18) (43 subjects). RESULTS: Twenty-five subjects (37%) met tilt table criteria for POTS. The median age of 16 years (range, 12-24 years) in the POTS group differed from 15 years (range, 6-21 years) in the no-POTS group (P = .03). Comorbidities including chronic fatigue, sleep disturbances, dizziness, syncope, migraines, functional gastrointestinal disorders, chronic nausea, fibromyalgia, and joint hypermobility did not differ between groups. All subjects with fibromyalgia by tender point-examination had a Beighton score ≥ 4 (P = .002). CONCLUSIONS: Comorbid conditions are equally prevalent in children and young adults with and without tilt-table defined POTS, suggesting that POTS itself is not a cause of the other comorbidities. Instead, POTS likely reflects another comorbid condition in children with functional disorders. Dizziness and syncope, classically associated with POTS, are not predictive of a diagnosis of POTS by tilt table, a test that is still required for formal diagnosis. These results suggest a paradigm shift in the concept of POTS as the physiological basis of many functional symptoms.

Arterial flow waveforms, vascular tone, and chronic fatigue: a case report.

We present the case of a patient with chronic fatigue secondary to Postural Orthostatic Tachycardia Syndrome (POTS) who had distinctive abnormalities in his arterial waveform morphology as assessed by pulse oximetry. Moreover, the patient's arterial waveform changed markedly from being supine to upright, suggesting that arterial flow patterns may be abnormal in our patient. Analysis of the waveform suggested a positional hypovolemia as the cause of his orthostatic intolerance. We review general aspects of arterial flow waveform analysis pertinent to health care providers and discuss the pathophysiology of POTS.

Joint hypermobility: a common association with complex functional gastrointestinal disorders.

OBJECTIVE: To evaluate the prevalence of joint hypermobility (JH) and comorbid conditions in children and young adults referred to a tertiary care neurogastroenterology and autonomic disorders clinic for functional gastrointestinal complaints. STUDY DESIGN: This was a retrospective chart review of 66 new patients aged 5-24 years who fulfilled at least 1 pediatric Rome III criteria for a functional gastrointestinal disorder (FGID) and had a recorded Beighton score (n = 45) or fibromyalgia tender point score (n = 45) based on physician examination. Comorbid symptoms were collected and autonomic testing was performed for evaluation of postural tachycardia syndrome (POTS). RESULTS: The median patient age was 15 years (range, 5-24 years), 48 (73%) were females, and 56% had JH, a significantly higher rate compared with population studies of healthy adolescents (P < .001; OR, 10.03; 95% CI, 5.26-19.13). POTS was diagnosed in 34% of patients and did not correlate significantly with hypermobility. Comorbid conditions were common, including sleep disturbances (77%), chronic fatigue (93%), dizziness (94%), migraines (94%), chronic nausea (93%), and fibromyalgia (24%). CONCLUSION: JH and other comorbid symptoms, including fibromyalgia, occur commonly in children and young adults with complex FGIDs. POTS is prevalent in FGIDs but is not associated with hypermobility. We recommend screening patients with complex FGIDs for JH, fibromyalgia, and comorbid symptoms such as sleep disturbances, migraines, and autonomic dysfunction.

Gastrointestinal manifestations of pediatric autonomic disorders.

Functional gastrointestinal disorders (FGIDs) are currently classified under the Rome criteria based on symptoms and absence of organic disease. Preliminary studies have shown that FGIDs are probably not restricted to the GI tract, but may represent a systemic disorder with comorbidities affecting other parts of the body, including migraine, fatigue, aches and pains, etc. The autonomic nervous system (ANS) provides the extrinsic control of GI motility, secretions, and even immune response. The role of the ANS in the development of FGIDs and comorbidities is still unclear. Limited data demonstrate orthostatic intolerance such as reflex syncope and postural tachycardia syndrome in a large subset of subjects with FGIDs. Some studies have found improvement in the GI symptoms with treatment of the orthostatic intolerance it produces. Prospective studies are needed to determine the chronology of the development of the comorbidities, the triggers that induce these syndromes, and effective treatments. This chapter aims to review current understanding of the role of the ANS in FGIDs.

The primary practice physician program for chronic pain (© 4PCP): outcomes of a primary physician-pain specialist collaboration for community-based training and support.

OBJECTIVES: One in 3 patients sees a primary care physician (PCP) for chronic pain yet most PCPs receive no training in this field. We evaluated the impact of 4PCP (© Primary Practice Physician Program for Chronic Pain) comprising of a specialist-PCP training collaboration integrated with clinical support. METHODS: This prospective, controlled pilot study randomly assigned 31 physicians to receive a training program either immediately or after a 1-year control period. 4PCP includes: (1) an active learning arm, providing patient-focused, practice-based learning collaboration emphasizing the biopsychosocial pain model; (2) a PCP-led clinical support arm facilitating rehabilitative matrix style care by teams of pain-informed health providers. Main outcome measures included a 19-item chronic pain physician perspectives questionnaire, physician engagement through continuing medical education hours earned, and an array of established measures of patient pain and function. RESULTS: PCPs receiving the intervention reported improvements in diagnosing and managing chronic pain (P=0.023), especially its functional consequences (P=0.008), in treatment satisfaction, and in involving other disciplines. Mean visit time dropped from 20 to 11 minutes (P<0.03) with improved patient outcomes, which correlated with 4PCP physician engagement. Significant benefit began at 10 continuing medical education hours and proved durable 1 year after trial. DISCUSSION: This pilot study demonstrates successful interdisciplinary chronic pain management by PCPs with durability of training effect, improved patient outcomes, visit efficiency, and job satisfaction. 4PCP provides a promising framework to propel the national concept of PCP-specialist collaboration for chronic pain management.

Autonomic testing in healthy subjects: preliminary observations.

INTRODUCTION: Autonomic testing is used clinically. Yet, the prevalence of "abnormal" variants in the healthy population has not been reported. RESULTS: We report the results of autonomic testing in healthy females >18 years, in whom we found decrease or absent sudomotor function in 1-2 locations. CONCLUSIONS: These findings should caution physicians in the interpretation of autonomic testing. This report underscores the need of larger studies to determine the prevalence of these findings.

Autonomic dysfunction in women with chronic pelvic pain.

We compared the Autonomic Symptom Profile results in 16 women with chronic pelvic pain (CPP) and 15 age-matched healthy subjects. Moderately severe generalized autonomic symptomology occurs in women with CPP, but not in controls. Further study including autonomic testing is needed to confirm results and explore the mechanism of dysfunction.

Complex [corrected] regional pain syndrome: what specialized rehabilitation services do patients require?

Complex [corrected] regional pain syndrome (CRPS) is a complex disorder, the optimal treatment of which requires an interdisciplinary approach encompassing medical, interventional, psychological, and rehabilitation services that emphasize the role of physical and occupational therapies. The central focus of treatment is the restoration of function, utilizing a systematic, coordinated, and progressive set of therapeutic strategies. The poorly delineated pathophysiology and variable course of CRPS suggest that individualized strategies are required for optimal management, but also mean that carefully controlled trials of physiotherapy are difficult to conduct. This article presents a brief review of the nature and pathophysiology of CRPS, the medical and psychological approaches that have been found to be effective, and a review of the current trends in rehabilitation.

Syncopal migraine.

OBJECTIVE: A subgroup of syncope patients report migraine headaches immediately preceding or following syncope, and some respond to anti-migrainous prophylactic agents. This study aimed to describe the frequency of migrainous features concurrent with episodes of syncope and to propose clinical criteria for assessing whether a migrainous mechanism might underlie syncope. METHODS: This retrospective, questionnaire-based study developed criteria for syncopal migraine based on the International Classification of Headache Disorders II (ICHD-II) migraine criteria. Two hundred and forty-eight recurrent syncope subjects (>3 episodes) were stratified based on the presence (N = 127) or absence (N = 121) of a headache concurrent with syncopal episodes. Syncopal headaches were classified as either syncopal migraine (meeting ICHD-II criteria for migraine or probable migraine, without aura) or nonspecific (not meeting the criteria for syncopal migraine). The syncope groups were then compared to 199 subjects with migraine headaches using chi-square and Cochran-Armitage test for trend. RESULTS: Nearly one-third of recurrent syncope subjects met criteria for syncopal migraine. This group resembled the migraine headache population more than the syncope population in age, gender, autonomic testing, and comorbid conditions. The syncopal migraine group also reported a longer duration of syncope and a longer recovery time to normal. Finally, anti-migrainous medications reduced syncope in half of the syncopal migraine subjects. INTERPRETATION: Syncope may have a migrainous basis more commonly than previously suspected, and we suggested criteria to identify these patients. Syncopal migraine appears epidemiologically more closely related to migraine than to reflex syncope.