Comparison of Voiding Dysfunction Phenotypes in Women with Interstitial Cystitis/Bladder Pain and Myofascial Pelvic Pain: Results from the ICEPAC Trial.

OBJECTIVE: To evaluate whether voiding parameters differ in patients with the common overlapping pelvic pain disorders, interstitial cystitis/bladder pain syndrome (IC/BPS), and myofascial pelvic pain (MPP). METHODS: Uroflow and voiding diary assessed voiding phenotypes in this prospective cohort study (ICEPAC) of women comparing IC/BPS, IC/BPS +MPP, MPP, and healthy control (HC) subjects. RESULTS: In 36 HC, 24 IC/BPS, 37 IC/BPS + MPP, and 14 MPP subjects, the voiding diary measurements indicate lower voided volumes in IC/BPS and IC/BPS + MPP groups (185 ± 24 mL, 169 ± 20 mL, respectively) compared to HC and MPP groups (294 ± 24 mL, 226 ± 36 mL, respectively; P <.05, P <.05), as well as higher 24-hour voiding frequency (11.6 ± 0.8 and 11 ± 1.2 voids/24 hours, respectively; HC 7.1 ± 0.5 voids/24 hours; P <.05, P <.05; MPP group 9 ± 1.2 voids/24 hours; P <.05, P <.05). Uroflow showed higher HC average flow rate (12.87 ± 0.92) compared to IC/BPS, IC/BPS+MPP, and MPP (8.31 ± 1.20, 8.02 ± 0.80, 8.17 ± 1.38, respectively; P <.01, P <.01, P <.05) and peak flow rate (27.0 ± 1.83) and IC/BPS, IC/BPS+MPP and MPP (16.20 ± 2.2, 17.33 ± 1.64, 17.21 ± 2.69 respectively; P <.01, P <.01, P <.05). CONCLUSION: This quantitative evaluation of voiding diary and uroflow metrics reveals distinct voiding phenotypes, which can aid in the diagnosis of chronic pelvic pain syndromes. Patients with IC/BPS had more pain with a full bladder despite similar overall pain scores. Peak and average flow rates do not provide any differentiating power between IC/BPS and MPP patients. A longer time to peak flow may favor MPP though this finding needs confirmation.

Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease.

BACKGROUND: Formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson's disease and those with multiple system atrophy (MSA), but such studies segregate patients according to clinical criteria that select those with autonomic dysfunction for the MSA category. OBJECTIVE: To characterise the profiles of autonomic disturbances in patients in whom the diagnosis of Parkinson's disease or MSA used criteria other than autonomic dysfunction. METHODS: 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features. They were classified clinically into three diagnostic groups: Parkinson's disease (19), MSA (14), and uncertain (14). The performance of the patients with Parkinson's disease was compared with that of the MSA patients on five autonomic tests: RR variation on deep breathing, heart rate changes with the Valsalva manoeuvre, tilt table testing, the sudomotor axon reflex test, and thermoregulatory sweat testing. RESULTS: None of the tests distinguished one group from the other with any statistical significance, alone or in combination. Parkinson's disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions. CONCLUSIONS: This study supports the clinical observation that Parkinson's disease is often indistinguishable from MSA when it involves the autonomic nervous system. The clinical combination of parkinsonism and dysautonomia is as likely to be caused by Parkinson's disease as by MSA. Current clinical criteria for Parkinson's disease and MSA that direct patients with dysautonomia into the MSA group may be inappropriate.

The clinical thermoregulatory sweat test induces maximal sweating.

Although thermoregulatory sweat testing is commonly used to assess the autonomic nervous system, the power of this stimulus to induce sweating has not been studied. In 8 healthy male subjects, the authors quantitated sweat rates, core temperature, heart rate, and blood pressure during clinical thermoregulatory sweat testing, a separate exercise protocol, and with exercise added to thermal conditions. The authors found that (1) the addition of exercise to the thermal environment produced no further increase in sweat rate (3,841+/-948 versus 3,888+/-866 nl/mn - cm2); (2) maximum sweat rates closely corresponded to the theoretical maximum (6,000 nl/mn - cm2) derived from single gland studies; (3) sweat rates vary across subjects, but are similar across sites in any one individual; (4) core temperature rise is a major determinant of cardiovascular load in both thermal and exercise settings; (5) blood pressure decreased 28/11 mm Hg during thermal load, but increased 26/10 mm Hg with exercise, in agreement with current understanding of muscle and skin vascular physiology. The authors conclude that clinical thermoregulatory testing conditions produce maximum sweat rates in humans.

Autonomic abnormalities in children with functional abdominal pain: coincidence or etiology?

BACKGROUND: There is increasing evidence that autonomic neuropathies may adversely affect gastrointestinal motility by involving the extrinsic nerves of the gut. The authors' hypothesize that functional abdominal pain in children is associated with generalized autonomic dysfunction. METHODS: The authors performed detailed autonomic testing in eight patients with functional abdominal pain, including deep breathing, Valsalva, tilting (to assess parasympathetic and sympathetic adrenergic function), and axon-reflex function and thermoregulatory sweat testing to assess sympathetic cholinergic function. Patients also completed a questionnaire regarding other autonomic symptoms. RESULTS: Results of autonomic testing were abnormal in seven patients. Parasympathetic function was normal in all, and the abnormalities were restricted to sympathetic cardiac, vasomotor, and sudomotor function. Abnormal results of axon-reflex testing in six were consistent with peripheral nervous system dysfunction. Five had decreased sweating over the abdomen, determined by thermoregulatory sweat testing. Five eight had nongastrointestinal autonomic symptoms, primarily palpitations and flushing. CONCLUSIONS: Functional abdominal pain in the current patients is associated with generalized dysfunction of the autonomic nervous system. This dysfunction can be peripheral or central in different individuals but seems to be restricted to the sympathetic branch. The known function of the sympathetic nervous system as the motility "brake" suggests that pain could be a manifestation of unmodulated peristalsis, resulting in abdominal cramps.

Alpha-adrenergic supersensitivity of the sudomotor nerve in complex regional pain syndrome.

alpha-Adrenoreceptor supersensitivity in many tissues has been described in patients with complex regional pain syndrome type I (CRPS I). Because excessive sweating of the affected limb is an important feature of CRPS I, we investigated whether this supersensitivity also occurs in the sudomotor system. We compared the sweat response to iontophoresis of an alpha-adrenergic agent (phenylephrine) in 4 patients with acute CRPS I and 3 patients with resolved CRPS I with that in 9 control subjects using the methodology of the quantitative sudomotor axon reflex test (QSART). A significantly higher sweat response was observed in the affected limb of patients with acute CRPS I compared to their unaffected limb (p = 0.03), to control subjects (p > 0.018), and to the affected or unaffected limbs of patients with resolved CRPS I (p = 0.02), whose sweat response was not significantly different from that of control subjects. We conclude that the abnormal response in patients with acute CRPS I is most likely mediated by an axon reflex and that alpha-adrenoreceptor supersensitivity occurs in the presynaptic portion of the postganglionic sudomotor axon. This supersensitivity is reversed when CRPS I resolves.

Lower body negative pressure: a test of cardiovascular autonomic function.

Lower body negative pressure (LBNP) may provide an alternative test of cardiovascular autonomic function for patients unable to perform the Valsalva maneuver (VM). LBNP at -40 mmHg for 30 s was compared to the VM at 40 mmHg for 15 s with heart rate and blood pressure measured continuously in three age groups: 10-25 years; 26-40 years; and 41-55 years. Heart rate and blood pressure responses were comparable, with moderately diminished changes in blood pressure and heart rate in the LBNP test. When heart response to LBNP was converted to a ratio similar to that calculated for the VM, a high degree of correlation was found (R(2) = 0.5711). The LBNP test shows promise as an alternative test of cardiovascular autonomic function based on studies in normal subjects. The less marked changes may relate to the more passive nature of the applied stress. Future work should improve the device's accessibility and establish values for patients with autonomic disorders.

Familial association of autonomic and gastrointestinal symptoms.

Autonomic dysfunction occurs in the adult population with irritable bowel syndrome, but this association is not recognized in children. A mother and son with functional abdominal pain unresponsive to conventional treatment had complete resolution of symptoms with treatment directed at the autonomic dysfunction identified by testing. The authors recommend autonomic testing in patients with functional abdominal pain and suggest that autonomic dysfunction plays a direct and intrinsic role in the mechanism of these disorders and their symptoms.

Value of autonomic testing in reflex sympathetic dystrophy.

OBJECTIVE: To attempt to characterize reflex sympathetic dystrophy (RSD) and to determine factors that would predict a response to sympathetic block. DESIGN: We undertook a retrospective analysis on 396 patients with chronic limb pain referred for autonomic testing during a 5-year period. MATERIAL AND METHODS: Clinical endpoints were relief of pain after sympathetic block and a composite RSD diagnostic probability score, based on the clinical attributes of allodynia, protopathia, swelling, and vasomotor alterations. We compared the results of three autonomic tests--resting sweat output (RSO), resting skin temperature (RST), and quantitative sudomotor axon reflex test (QSART). RESULTS: Increased RSO predicted the diagnosis of RSD with 94% specificity, and the specificity was 98% when RSO was considered in conjunction with an abnormal QSART result, the best laboratory correlate (P = 0.003) of the clinical diagnosis. Shorter duration of pain correlated with a warmer limb (P < 0.001), even in the absence of RSD. Response to a single sympathetic block did correlate with the diagnosis (P = 0.031) but correlated most significantly with short duration of pain in the arm (P = 0.001) and laboratory findings in the leg, where increased RST (P < 0.001) and QSART (P < 0.001) were near-perfect predictors of response. CONCLUSION: Sweating abnormalities correlate strongly with the clinical syndrome of RSD, and alterations in RST may be superior to clinical findings in predicting the response to sympathetic block. The findings provide physiologic support for the unproven view of a natural disease progression ("stages"), with better treatment response and a warmer extremity initially. Because certain physiologic trends occur in all patients, general alterations of autonomic function with pain are suggested.

Utility of thermography in the diagnosis of lumbosacral radiculopathy.

We performed infrared telethermography in 55 patients with the clinical diagnosis of lumbosacral radiculopathy and in 37 normal controls. Five readers interpreted the thermograms in a blinded fashion. A moderate degree of agreement was noted in tests of intraobserver and interobserver variability. The sensitivity of thermography ranged from 78% to 94% compared with 81% to 92% for imaging studies and 77% for EMG. The specificity of thermography ranged from 20% to 44%. Thermography predicted the level of the radiculopathy correctly in less than 50% of cases. Thermography has little or no utility in the diagnosis of lumbosacral radiculopathy.

A cytoarchitectonic and histochemical study of nucleus basalis and associated cell groups in the normal human brain.

Several recent studies have reported loss of neurons in the nucleus basalis in Alzheimer's disease. However, few detailed studies of the normal distribution of these neurons in the human brain have appeared. We have used Nissl staining and acetylcholinesterase histochemical staining of the human basal forebrain, alone or in combination to identify the organization of the nucleus basalis and associated cell groups, (or collectively, the magnocellular basal nucleus) in the normal human brain. The magnocellular basal nucleus includes a series of clusters of neurons and scattered perikarya extending from the medial septum and diagonal band nucleus rostrally, through the substantia innominata to the furthest caudal extent of the globus pallidus. This distribution is similar to that which has been described in the monkey. Furthermore, acetylcholinesterase-positive fibers in the human brain are seen in the two major pathways that have been identified as carrying magnocellular basal nucleus axons to the cerebral cortex in other species. These observations suggest that the topographic organization of the magnocellular basal projection to cerebral cortex in other species probably exists in man as well. It will therefore be important in future studies of the fate of these neurons in neurological degenerative diseases to assess the loss of neurons in the different components of the magnocellular basal nucleus in relation to the clinical evidence for dysfunction in the cortical areas which they innervate.