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.

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.

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.

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.

Comorbid health conditions in women with syncope.

OBJECTIVE: We determine the comorbid conditions associated with syncope in women. In addition, we hypothesize a higher proportion of autonomic comorbid conditions during the female reproductive age. METHODS: We identified a cohort of patients admitted to US hospitals with the principal diagnosis of syncope. We compare patient demographics stratified by gender as well as syncope associated comorbidities. We compared these comorbidities in female of reproductive age (15-45) to men as control. RESULTS: From a total sample of 305,932, females constituted 56.7% (n = 173,434). Females were slightly older (mean age 70.9 +/- 17.9 vs. 66.7 +/- 17.3; P < 0.0001); with similar racial distribution (white 57.8 vs. 57.5%), and similar length of hospital stay (mean 2.66 +/- 2.63 vs. 2.68 +/- 2.72 days; P > 0.05). Females had higher proportion of migraine (1.65 vs. 1.29%; odds ratio 'OR' 1.29; 95% confidence interval 'CI' 1.21, 1.36); chronic fatigue syndrome (1.73 vs. 1.3%; OR 1.32; 95% CI 1.25, 1.4); gastroparesis (0.2 vs. 0.12%; OR 1.64; 95% CI 1.35, 1.98); interstitial cystitis (0.07 vs. 0.01%; OR 7.44; 95% CI 4.10, 13.5); and postural tachycardia syndrome (0.49 vs. 0.44%; OR 1.1; 95% CI 1.001, 1.23). Orthostatic hypotension was not different between the groups (P = 0.24). When the sample was stratified by age category, the odds ratio for gastroparesis, orthostatic hypotension, and postural tachycardia syndrome was increased (P < 0.05). INTERPRETATION: A higher proportion of autonomic dysfunction was present in women compared to men. In addition, these comorbid autonomic conditions were especially prominent during the female reproductive age.

The serum of dysautonomia patients enhances proliferation and signaling in Schwann cells.

Disorders of the autonomic nervous system, or dysautonomias, affect a large segment of the population, especially women, and represent a diagnostic challenge. Identification of biomarkers for autonomic disorders, and the subsequent development of screening methods, would benefit diagnosis and symptom management. We studied the effect of sera from fifteen well-characterized dysautonomia patients (mean age 49+/-16 years, 10 females, 5 males) and ten control subjects (mean age 31+/-14 years, 5 females, 5 males) on the proliferation of cultured Schwann cells and activity of mitogen-activated protein kinases (MAPKs) in these cells. We correlated characteristics of patients with the effects on cell proliferation and signaling. Overall, we observed a significant increase in proliferation when Schwann cells were incubated with sera from female dysautonomia patients when compared to control subjects and male patients. Interestingly, removal of IgGs significantly reduced the proliferative effect of patient sera. We also observed significant activation of p38 MAPK following incubation with both male and female patient sera. These results suggest that patient sera contain factors that contribute to aberrant Schwann cell proliferation and signaling and may ultimately lead to autonomic nerve dysfunction. Our observations represent a promising first step in the identification of dysautonomia biomarkers.

Cough-induced hemiplegic migraine with impaired consciousness in cystic fibrosis.

The coughing paroxysms of patients with cystic fibrosis may occasion neurological symptoms. Although cough syncope is well-known, and is associated with headache and paralysis, a migrainous mechanism has not been reported. We reviewed the medical records, autonomic testing results, and responses to treatment in two cystic fibrosis patients with similar presentations of cough-induced impairment of consciousness followed by headache and paralysis. A 24-year-old woman and an unrelated 38-year-old man, both with cystic fibrosis, developed post-tussive neurologic deficits. Both patients reported infrequent dramatic spells, always preceded by major hemoptysis, and associated with left-sided paralysis, transient blindness, nausea, and severe pulsating headaches. Autonomic testing demonstrated only postural tachycardia and a near-vasodepressor episode in the woman, and mild, generalized sympathetic dysfunction in the man. Treatment for presumptive migraine with aura with verapamil nearly eradicated symptoms in both patients. Discontinuation of verapamil in the woman was associated with symptom recurrence and a stroke, with significant persistent residual left hemiparesis. In conclusion, cough-induced neurologic deficits were previously reported with cystic fibrosis, without clear understanding of the mechanism of impairment of consciousness. Based on the hemiparesis, nausea, and throbbing headache, which repeatedly followed the events in both patients, and based on the response to verapamil, we hypothesize a migrainous mechanism in both of our patients. The pathophysiology that links the hemoptysis to the spells deserves further investigation.