Postganglionic Sudomotor Research Articles

Unraveling Autonomic Dysfunction in GBA-Related Parkinson's Disease.

Patients with Parkinson's disease (PD) and GBA gene mutations (GBA-PD) develop nonmotor complications more frequently than noncarriers. However, an objective characterization of both cardiovascular and sudomotor autonomic dysfunction using extensive clinical and instrumental measures has never been provided so far. Survival is reduced in GBA-PD regardless of age and dementia, suggesting that other hitherto unrecognized factors are involved. To provide instrumental measures of pattern and severity of autonomic dysfunction in GBA-PD and explore their correlation with other non-motor symptoms and implications for clinical practice. In this cross-sectional study, 21 GBA-PD and 24 matched PD noncarriers underwent extensive assessment of motor and non-motor features, including neuropsychological testing. Cardiovascular autonomic function was explored through a comprehensive battery of indexes, including power spectral analysis of the R-R intervals and blood pressure short-term variability during resting state and active maneuvers. Dynamic Sweat Test was used to assess post-ganglionic sudomotor dysfunction. Despite minimal or absent clinical correlates, cardiovagal and sympathetic indexes, heart rate variability parameters and sudomotor postganglionic function were more severely impaired in GBA-PD than noncarriers (overcoming relatively preserved compensatory peripheral sympathetic function), suggesting more prominent cardiac sympatho-vagal demodulation, efferent baroreflex failure and peripheral sympathetic dysfunction in GBA-PD. Cardiovascular dysautonomia showed marginal correlations with cognitive impairment. Compared to PD noncarriers, GBA-PD display more severe instrumental autonomic abnormalities, which may be underestimated by purely clinical measures, despite their relevance on morbidity and mortality. This supports the necessity of implementing instrumental autonomic assessment in all GBA-PD, regardless of clinically overt symptoms.

Updates on the Diagnosis and Treatment of Peripheral Autonomic Neuropathies.

Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies. Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical-physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.

Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study.

Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), with the latter characterized by diffuse anhidrosis in prospective study, including patients in late stage of disease. We aimed to evaluate morphologic and functional postganglionic sudomotor involvement in patients with newly diagnosed MSA-P and PD to identify possible biomarkers that might be of help in differentiating the 2 conditions in the early stage. One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At the time of recruitment, questionnaires to assess nonmotor, autonomic, and small fiber symptoms were administered, and patients underwent postganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from the distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies, including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured on confocal images with dedicated software. A follow-up visit 12 months after recruitment was performed to confirm the diagnosis. We recruited 57 patients with PD (M/F 36/21, age 63.5 ± 9.4 years) and 43 patients with MSA-P (M/F 27/16, age 62.3 ± 9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in patients with MSA-P compared to those with PD. Sweating output and intraepidermal, pilomotor, and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in patients with MSA-P. Pilomotor and sudomotor nerve density correlated with sweating function and with nonmotor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers efficiently separated the 2 populations; the receiver operating characteristics curve showed an area under the curve of 0.83. Dynamic sweat test and the quantification of cutaneous autonomic nerves proved to be a sensitive morpho-functional approach to assess the postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to differentiate the 2 conditions early. This study provides Class II evidence that postganglionic sudomotor morpho-functional assessment accurately distinguish patients with PD from patients with MSA-P.

Segmental anhidrosis and heat intolerance

A 62 year-old woman with no previous medical history presented to the Dermatology department with sweating disorders for several years. She described segmental hyperhidrosis and hyperemia while running. This excessive sweating occurred in the left hemiface, the left half of the trunk, the left upper limb and the right lower limb (Fig. 1A). This was associated with heat intolerance and previous faintness during sport. She did not describe any chest pain before faintness and the cardiac auscultation was normal. The neurological examination revealed a diffuse areflexia in the absence of any sensory or motor disorders. By illuminating the right eye, we observed a delay in ipsilateral pupillary contraction, whereas we observed an absence of the consensual photomotor reflex of the right eye by illuminating the left eye (Adie's tonic pupil, Fig. 1B and C, and Supplementary file 1). However, she did not complain of reduced visual acuity. Ross syndrome is a rare autonomic disorder caused by a selective degenerative process of the postganglionic cholinergic sudomotor neurons [[1]Sommer C. Lindenlaub T. Zillikens D. Toyka K.V. Naumann M. Selective loss of cholinergic sudomotor fibers causes anhidrosis in Ross syndrome.Ann Neurol. 2002; 52: 247-250Google Scholar]. Ross syndrome is diagnosed by the presence of a triad of symptoms associating segmental anhidrosis (with compensatory hyperhidrosis), Adie's tonic pupil and areflexia [[2]Mishra A.K. Kharkongor M. Kuriakose C.K. George A.A. Peter D. Carey R.A.B. et al.Is ross syndrome an autoimmune entity? A case series of 11 patients.Can J Neurol Sci. 2017; 44: 318-321Google Scholar]. The main complaint of patients is generally the segmental compensatory hyperhidrosis, the anhidrosis in contrast is not even noticed. The two other signs must be specifically examined for to make the diagnosis. The deep tendon hyporeflexia or areflexia affects the four limbs, whereas the tonic pupil is observed on the pathological and anhidrotic side of the face. It has been proposed to treat hyperhidrosis with botulinum toxin [[3]Bergmann I. Dauphin M. Naumann M. Flachenecker P. Müllges W. Koltzenburg M. et al.Selective degeneration of sudomotor fibers in Ross syndrome and successful treatment of compensatory hyperhidrosis with botulinum toxin.Muscle Nerve. 1998; 21: 1790-1793Google Scholar], but this treatment may theoretically increase the heat intolerance and the risk of faintness during sport. Even if the disorder is benign, the objective is to avoid any faintness. Clinicians should advise patients with Ross syndrome to wear light clothing for sports and to avoid excessive heat exposure.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Postganglionic Sudomotor Dysfunction and Brain Glucose Hypometabolism in Patients with Multiple System Atrophy.

Sudomotor dysfunction is common in patients with multiple system atrophy (MSA). Postganglionic sudomotor dysfunction in MSA, which can be assessed using quantitative sudomotor axon reflex testing (QSART), results from the degeneration of preganglionic sympathetic neurons and direct loss of postganglionic fibers. We investigate whether abnormal QSART responses in patients with MSA are associated with disease severity. In this retrospective study, patients with probable MSA who underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and autonomic function tests were included. Autonomic function test results were integrated divided into three sub-scores, including sudomotor, cardiovagal, and adrenergic sub-scores. The sudomotor sub-score represented postganglionic sudomotor function. Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, Part II, and sum of Part I and II scores (Part I + II) to reflect disease severity and 18F-FDG-PET/CT results were collected. Of 74 patients with MSA, 62.2%demonstrated abnormal QSART results. The UMSARS Part I + II score was significantly higher in the abnormal QSART group than in the normal QSART group (p = 0.037). In the regression analysis, both UMSARS Part I (β= 1.185, p = 0.013) and Part II (β= 1.266, p = 0.021) scores were significantly associated with the sudomotor sub-score. On 18F-FDG-PET/CT, the abnormal QSART group exhibited more severely decreased metabolic activity in the cerebellum and basal ganglia in patients with MSA-P and MSA-C, respectively. The sudomotor sub-score was significantly associated with regional metabolism in these areas. Patients with MSA and postganglionic sudomotor dysfunction may have worse disease severity and greater neuropathological burden than those without.

Auxiliary Tests of Autonomic Functions.

The autonomic nervous system is a complex neural network that controls several organ systems. Its assessment includes a detailed history of autonomic functions, clinical examination, and autonomic tests. Most widely used is a battery of tests that assess cardiovascular reflex autonomic and sudomotor tests, which include deep breathing (assesses parasympathetic function), Valsalva maneuver, tilt test (both assess parasympathetic and adrenergic functions), and sudomotor testing for the evaluation of postganglionic sudomotor fibers. These basic tests represent a foundation of autonomic testing. Nevertheless, the autonomic nervous system also controls organ systems not directly assessed by basic tests. This review describes a number of auxiliary autonomic tests that can be used in addition to basic autonomic tests or can be used independently to explore particular autonomic functions or to answer a specific clinical question. The auxiliary tests described in this review evaluate cardiovascular, thermoregulatory, gastrointestinal, genitourinary, eye, and exocrine functions. These tests are cold pressor test, sustained handgrip maneuver, reverse tilt test, venoarteriolar reflex, laser Doppler flare imaging, microneurography, neck suction, lower body negative pressure, venous occlusion plethysmography, pharmacologic assessment of postganglionic sympathetic outflow, plasma norepinephrine, sympathetic skin response, video cinefluoroscopic swallowing test, esophageal manometry test, small bowel manometry test, wireless motility capsule test, urodynamic studies, penile plethysmography, intracavernosal papaverine injection, infrared video pupillography, corneal confocal microscopy, pupillary response to dilute pilocarpine and hydroxyamphetamine, Schirmer test, tear osmolarity test, and salivary secretion test. The protocol of each test is described in detail. This review can be used as a quick reference for the auxiliary autonomic tests.

Scientific review of the aesthetic uses of botulinum toxin type A.

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy.

The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response. We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head-up tilt. Eleven patients received immunotherapy. At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8-61.3] to 5.2 [1.4-8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0-3.3] to 4.5 [3.0-6.3], p = 0.02), pupillary constriction to light (12.0 [5.5-18.0] to 19.0 [10.6-23.8]%, p = 0.02), saliva production (0.01 [0.01-0.05] to 0.08 [0.02-0.20] g/min, p = 0.03), and COMPASS-31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753-768.

Sudomotor Dysfunction.

Disorders of sudomotor function are common and diverse in their presentations. Hyperhidrosis or hypohidrosis in generalized or regional neuroanatomical patterns can provide clues to neurologic localization and inform neurologic diagnosis. Conditions that impair sudomotor function include small fiber peripheral neuropathy, sudomotor neuropathy, myelopathy, α-synucleinopathies, autoimmune autonomic ganglionopathy, antibody-mediated hyperexcitability syndromes, and a host of medications. Particularly relevant to neurologic practice is the detection of postganglionic sudomotor deficits as a diagnostic marker of small fiber neuropathies. Extensive anhidrosis is important to recognize, as it not only correlates with symptoms of heat intolerance but may also place the patient at risk for heat stroke when under conditions of heat stress. Methods for assessing sudomotor dysfunction include the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, silicone impressions, and the sympathetic skin response.

Quantitative sudomotor abnormalities in clinically isolated rapid eye movement sleep behavior disorder.

Post-ganglionic sudomotor abnormalities are common in Parkinson's disease (PD), however data in clinically isolated REM sleep behavior disorder (iRBD) are limited. To determine the prevalence of sudomotor abnormalities in a cohort of patients with iRBD. We performed a retrospective review of patients seen in our autonomic clinic who underwent testing with the quantitative sudomotor axon reflex test (QSART). We identified three groups for comparison: 1.) iRBD, 2.) PD with RBD (PDwRBD) 3.) PD without RBD (PDwoRBD). PDwRBD (n=27) patients demonstrated the greatest sudomotor abnormalities (sudomotor CASS 1.44±1.24), followed by PDwoRBD (n=23, 0.57±0.5) and iRBD (n=20, 0.55±0.94) (p=0.015). Twenty percent of patients with iRBD had an abnormal result, compared to 67% PDwRBD and 35% PDwoRBD. Sudomotor abnormalities are common in patients with iRBD, supporting the concept that peripheral autonomic impairment occurs early in the course of disease.

Assessment of sudomotor function.

To review the currently available literature on clinical autonomic tests of sudomotor function. We searched PubMED/MEDLINE for articles on technical principles and clinical applications of sudomotor tests with a focus on their drawbacks and perspectives in order to provide a narrative review. The quantitative sudomotor axon reflex sweat test (QSART) is the most widely used test of sudomotor function. The technique captures pathology with low intra- and inter-subject variability but is limited by technical demands. The thermoregulatory sweat test comprises topographic sweat pattern analysis of the ventral skin surface and allows differentiating preganglionic from postganglionic sudomotor damage when combined with a small fiber test such as QSART. The sympathetic skin response also belongs to the more established techniques and is used in lie detection systems due to its high sensitivity for sudomotor responses to emotional stimuli. However, its clinical utility is limited by high variability of measurements, both within and between subjects. Newer and, therefore, less widely established techniques include silicone impressions, quantitative direct and indirect axon reflex testing, sensitive sweat test, and measurement of electrochemical skin conductance. The spoon test does not allow a quantitative assessment of the sweat response but can be used as bedside-screening tool of sudomotor dysfunction. While new autonomic sudomotor function testings have been developed and studied over the past decades, the most were well-studied and established techniques QSART and TST remain the gold standard of sudomotor assessment. Combining these techniques allows for sophisticated analysis of neurally mediated sudomotor impairment. However, newer techniques display potential to complement gold standard techniques to further improve their precision and diagnostic value.

T130. Quantitative sudomotor axon reflex testing in anterior horn cell disorders

Autonomic disturbances in the form of hyperhidrosis, stiffness of fingers and aggravation of motor weakness on exposure to cold(Cold paresis) has been reported in anterior horn cell disorders like early stages of Amyotrophic lateral sclerosis (ALS), Brachial Monomelic Amyotrophy (BMMA) and Distal Bimelic Amyotrophy (DBMA). Quantitative sudomotor axon reflex test (QSART) was done to assess the functional integrity of postganglionic sympathetic sudomotor axons. 25 patients of BMMA, 10 patients with DBMA divided into two groups based on age (Group1: 20–30 years and Group2: 30–40 years) and 10 patients with ALS where recruited for the study and compared with equal cohort of age matched controls. General physical examination and anthropometric measurements were taken before recording. Sudomotor function of the study participants were evaluated by using Q-Sweat device manufactured by WR Medical Electronics. Resting sweat rate was recorded 5 min followed by iontophoretic stimulation. Baseline sweat volume, Total sweat volume and latency time from start of iontophoretic stimulation [acetylcholine-2 mA current strength for 5 min] to sweat response from 4 recording sites were measured. The variances in parameters like age, body weight, both height of both control and disease group were not significantly different and hence comparable. The mean age of BMMA patients: [Group1: 22.8 ± 3.8 and Group2: 33.8 ± 3.2 years] age matched controls - [Group1: 25.4 ± 2.7 and Group2: 35.1 ± 2.8 years]. There was no significant difference in baseline line sweat rate, latency and total sweat volume between controls and patients at four sites viz. Forearm, Proximal leg, Distal leg and Foot in both affected and unaffected limb. There was no significant difference between affected and unaffected limbs in above parameters in patients with BMMA. Similar results were obtained for patients in early stages of ALS (mean age 46.8 ± 3.2 years) and DBMA [Group1: 23.3 ± 4.8 and Group2: 38.0 ± 2.9 years]. Our findings suggests normal functioning of post ganglionic sudomotor fibers in BMMA and DBMA. The highly prevalent autonomic symptoms probably arise due to pre-ganglionic autonomic dysfunction and possibly in the cervical cord.

Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction.

The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes. All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing. The majority of the 232 patients were MSA-parkinsonism (145, 63%). Initial postganglionic sudomotor testing was abnormal in 59%, whereas thermoregulatory sweat test was abnormal in 95% of all patients. MSA-parkinsonism patients were more likely to have an abnormal thermoregulatory sweat test compared with MSA-cerebellar (98% versus 90%, P = 0.006) and had a higher mean percentage of anhidrosis (57%) compared with MSA-cerebellar (48%; P = 0.033). Common anhidrosis patterns were regional (38%) and global (35%). The site of the lesion was preganglionic in 47% and mixed (preganglionic and postganglionic) in 41%. The increase in anhidrosis per year was 6.2% based on 70 repeat thermoregulatory sweat tests performed on 29 patients. The frequency of postganglionic sudomotor abnormalities increased over time. Our findings suggest: (1) sudomotor dysfunction is almost invariably present in MSA and even more common and severe in MSA-parkinsonism than MSA-cerebellar; (2) a preganglionic pattern of sweat loss is common in MSA; however, pre- and postganglionic abnormalities may coexist; and (3) the increasing frequency of postganglionic sudomotor dysfunction over time suggests involvement of postganglionic fibers or sweat glands later in the disease course. © 2016 International Parkinson and Movement Disorder Society.

Seasonal acclimation in sudomotor function evaluated by QSART in healthy humans.

The quantitative sudomotor axon reflex testing (QSART) is a classic test of routine postganglionic sudomotor function. We investigated sudomotor function by QSART after summer (July 2012) and winter (January 2013) seasonal acclimation (SA) in the Republic of Korea. QSART with acetylcholine (ACh) iontophoresis were performed to determine directly activated (DIR) and axon reflex-mediated (AXR1, 2) sweating rate. Onset time of axon reflex, activated sweat gland density (ASGD), activated sweat gland output (ASGO), tympanic and skin temperatures (Tty, Tsk), basal metabolic rate (BMR), and evaporative loss volume changes were measured. Tympanic and mean body temperature (Tb; calculated from Tty, Tsk) were significantly lower after summer-SA than that of winter-SA. Sweat onset time was delayed during winter-SA compared to that after summer-SA. BMR, AXR(1), AXR(2), and DIR sweat rates, ASGD and ASGO, and evaporative loss volume were significantly diminished after winter-SA relative to after summer-SA. In conclusion, changes in sweating activity measured by QSART confirmed the involvement of the peripheral nervous system in variation of sudomotor activity in seasonal acclimation.

The Peripheral Sympathetic Neuron is Intact in Alzheimer's Disease and Behavioral Variant of Frontotemporal Dementia.

The study was undertaken to evaluate the postganglionic sympathetic sudomotor function employing the quantitative sudomotor axon reflex test (QSART) in tauopathies Alzheimer's disease (AD) and behavioral variant of frontotemporal dementia (bvFTD). Patients were recruited in a prospective pilot study. A structured history was taken and QSART was recorded. In all, 15 patients with AD (7 female) and 14 patients with bvFTD (9 female) were included. Mean age (±standard deviation) of patients with AD and bvFTD was 74 ± 9 and 71 ± 10 years, respectively. Severe sudomotor dysfunction (Composite Autonomic Severity sudomotor score 3) was present in 3 (20%) patients with AD and 0 (0%) patients with bvFTD (P = .037). The upper extremity was only involved in 1 patient with AD and 1 patient with bvFTD. Sweat results of the 4 recording sites did not differ between both groups. Patients' history correlated with severe autonomic symptoms as assessed with QSART. Postganglionic sudomotor involvement in AD and bvFTD is most likely not part of the disease.

Postganglionic sudomotor denervation in patients with multiple system atrophy.

To evaluate postganglionic autonomic involvement in multiple system atrophy (MSA). We quantified sudomotor innervation in skin biopsy of 29 patients with MSA (19 male and 10 female; age 60.0 ± 7.7 years) and 29 age- and sex-matched healthy subjects. Samples were obtained from thigh and leg and, in 20 out of the 29 cases, also from fingertip. Dysautonomic complaints were evaluated by SCOPA-AUT, a self-administered questionnaire. Sudomotor function was evaluated in a subgroup of patients by the silastic imprint test. Skin samples were processed by indirect immunofluorescence using pan-neuronal and selective cholinergic markers. Total length of sudomotor nerves was measured on digital confocal images using a semiautomated morphometric approach. Measurements of sudomotor nerve density (total length of nerve per volume of glandular tissue) favorably correlated to values obtained using a stereologic unbiased method. Sudomotor nerve density was lower in patients compared to controls in all the examined sites (0.9 ± 0.2 vs 1.9 ± 0.4 nm/μm(3), p < 0.001, in fingertip; 0.7 ± 0.2 vs 1.9 ± 0.5 nm/µm(3), p < 0.001, in thigh; 0.6 ± 0.2 vs 1.8 ± 0.4 nm/µm(3), p < 0.001, in leg). Our data support the hypothesis that postganglionic impairment occurs in MSA and may contribute with the coexisting degeneration of central structures to the development of dysautonomic disorders in this condition.

5. Postganglionic sudomotor involvement in central neurodegenerative disorders

Sudomotor function is often impaired in peripheral (PNSd) and central nervous system disorders (CNSd). Mechanisms underlying sudomotor failure in CNSd are not always clear. However, recently an involvement of peripheral nervous system in central neurodegenerative diseases has been observed. Objective of this study is to try of clarifying the involvement of postganglionic sudomotor pathway in CNSd. We studied the peripheral portion of the sudomotor pathway in 22 patients affected by CNSd and 26 patients affected by PNSd, comparing our results to the data from our control group. Sweating at distal leg was evaluated by the dynamic sweat test, a technique able to assess postganglionic sudomotor function by evaluating gland density and sweat production. We observed an impairment of sudomotor function in both groups of patients compared to controls. The density of activated sweat glands per cm2 was 59.7 ± 29.8 in PNSd patients and 49.6 ± 19.6 in CNSd patients. Average sweat volume per single gland was 5.3 ± 3.6 nl in PNSd patients and 3.8 ± 1.5 in CNSd patients. Our data suggest that the peripheral portion of sudomotor pathway is impaired also in patients affected by CNSd.

52. Asymmetrical sudomotor impairment in Parkinson’s disease evaluated with SSR and DST

Our aim was to evaluate if autonomic impairment in Parkinson disease (PD) differently affects the primarily compromised side. Fourteen PD patients underwent bilateral sympathetic skin response (SSR) recording. The response was elicited on palms and soles following standard procedures. Patients underwent also sudomotor output evaluation by dynamic sweat test (DST), a technique able to assess postganglionic sudomotor function by evaluating gland density and sweat production. A significant (p < 0.01) reduction of sweating was observed in PD patients. An asymmetry of sudomotor output was present with a lower activation of sweat glands in the primarily affected side. SSR amplitude correlated with sudomotor impairment. Our data confirm that a distal hypohidrosis secondary to an involvement of postganglionic sudomotor fibers occurs in patients affected by idiopathic PD and preferentially involves the side primarily affected by the disease.

Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy

We read the work by Robinson-Papp et al. with interest. The authors report that 61 % of participants had autonomic dysfunction (AD) as defined by a composite autonomic severity score (CASS) >3, with peripheral nerve dysfunction being the strongest predictor, affecting 90 % of participants who have HIV-associated distal symmetric polyneuropathy. Eighty-six percent of individuals with AD were symptomatic on survey of autonomic symptoms (SAS). The Composite Autonomic Scoring Scale (CASS) is a validated scale designed to quantify autonomic failure. CASS is derived from three areas of autonomic function: adrenergic, cardiovagal, and sudomotor (1996; Weimer 2010; Low et al. 2008). A CASS of 6 is indicative of severe autonomic failure (Low et al. 2008). CASS has been correlated with cardiovascular disease events and mortality (Gehrking et al. 2013). A CASS of 4–6 has been associated with orthostatic hypotension, abnormal sweating, and gastrointestinal abnormalities and is usually seen in autonomic failure (Low 1993). The authors report a median CASS of 3, suggesting that 50 % of subjects had a CASS of >3. The study reported on the CASS upper range of 6. A CASS this high would implicate major clinical outcomes and mortality which frankly have not been seen in large epidemiologic studies. The rates and severity of AD may have been overestimated in this study. In a convenience sample of 48 virologically suppressed HIV-infected individuals with and without polyneuropathy, we reported on a median CASS of 1 (IQR 1), and 40 % of subjects were symptomatic. We utilized the Composite Autonomic Symptom Scale to measure autonomic symptoms, a better instrument to detect and quantitate AD compared to the SAS used in the study. We wonder whether using the Q-sweat test for evaluating the sudomotor response used in the study may have overestimated AD. The qualitative sudomotor axon reflex test (QSART) has been a routine postganglionic sudomotor function test of the Mayo Clinic since 1983. The Q-sweat test is a commercial quantitative sweat measurement test modeled on QSART, but can overestimate sudomotor dysfunction (Sletten et al. 2010). In the era of combination antiretroviral therapy (cART), dramatic improvements in morbidity and mortality have been witnessed. However, autonomic symptoms such as light-headedness, dry mouth and eyes, cold feet, and constipation, as noted in the study and ours, have become common complaints among HIV-infected patients. AD has been correlated with HIV disease progression (Becker et al. 1997; Chow et al. 2011). Individuals with AIDS receiving cART have better measures of autonomic function compared to individuals that are not on cART (Correia et al. 2006). Forty-two percent of the study participants had a detectable viral load. Early and lifelong suppression of HIV infection and avoidance of medications that cause peripheral neuropathy and metabolic disorders needs to be considered for HIV-infected individuals (Askgaard et al. 2011). AD is a common condition. The rate and severity of autonomic dysfunction may not appear as elevated as suggested by the authors. Nonetheless, we commend Robinson-Papp et al. for bringing attention to AD which we agree is an underappreciated condition that is becoming increasingly common among our aging HIV-infected patients. Further investigation is needed to explain the prevalence and nature of AD, and its potential treatment.