Blunted sudomotor reactivity in fibromyalgia is associated with levels of depression.

OBJECTIVES: Assessment of sudomotor function by distal electrochemical skin conductance (ESC) can provide an index of peripheral neuropathy. This study explored ESC in fibromyalgia (FM) patients, controlling for tricyclic antidepressant use and body mass index, and its association with the clinical severity of the disease. METHODS: ESC, clinical symptoms and an index of central pain sensitisation derived from pressure algometry were explored in thirty-three fibromyalgia patients and 33 healthy women. RESULTS: ESC was significantly lower in fibromyalgia patients than healthy participants. About 51% of patients exhibited moderate-to-severe ESC dysfunction, indicative of possible neuropathy. However, ESC was not related to any indicators of clinical severity, nor to algometry. ESC only correlated with depression levels; the group differences in ESC disappeared after controlling for depression. Finally, ESC was asymmetric in the overall sample, with lower values seen in the right hand relative to the left one. CONCLUSIONS: The greater prevalence of sudomotor dysfunction in fibromyalgia patients is consistent with the presence of neuropathy in subgroups of patients, and with the basic heterogeneity of the disorder. However, neuropathy does not appear helpful for determining the clinical features of the disorders, or the level of central sensitisation measured by pressure algometry. Future studies including patients with fibromyalgia suffering and not suffering from depression as well as patients with depression but free from chronic pain, are required to identify the role of depression in the observed low ESC levels.

Electrodermal signal analysis using continuous wavelet transform as a tool for quantification of sweat gland activity in diabetic kidney disease.

Sympathetic innervation of the sweat gland (SG) manifests itself electrically as electrodermal activity (EDA), which can be utilized to measure sudomotor function. Since SG exhibits similarities in structure and function with kidneys, quantification of SG activity is attempted through EDA signals. A methodology is developed with electrical stimulation, sampling frequency and signal processing algorithm. One hundred twenty volunteers participated in this study belonging to controls, diabetes, diabetic nephropathy, and diabetic neuropathy. The magnitude and time duration of stimuli is arrived by trial and error in such a way it does not influence controls but triggers SG activity in other Groups. This methodology leads to a distinct EDA signal pattern with changes in frequency and amplitude. The continuous wavelet transform depicts a scalogram to retrieve this information. Further, to distinguish between Groups, time average spectrums are plotted and mean relative energy (MRE) is computed. Results demonstrate high energy value in controls, and it gradually decreases in other Groups indicating a decline in SG activity on diabetes prognosis. The correlation for the acquired results was determined to be 0.99 when compared to the standard lab procedure. Furthermore, Cohen's d value, which is less than 0.25 for all Groups indicating the minimal effect size. Hence the obtained result is validated and statistically analyzed for individual variations. Thus this has the potential to get transformed into a device and could prevent diabetic kidney disease.

Long-Term Efficacy of T3 Versus T3+T4 Thoracoscopic Sympathectomy for Concurrent Palmar and Plantar Hyperhidrosis.

BACKGROUND: More than 50% of patients with palmar hyperhidrosis (PAH) also have plantar hyperhidrosis (PLH). We compared the long-term results of T3 sympathectomy with those of combined T3+T4 sympathectomy among patients with concurrent PAH and PLH. MATERIALS AND METHODS: We retrospectively analyzed the records of patients with concurrent PAH and PLH who underwent T3 alone or T3+T4 sympathectomy from January 1, 2012, to December 31, 2017. Preoperative and postoperative sweating (hyperhidrosis index) was evaluated through questionnaires, physical examination, and outpatient follow-up. The relief rates and hyperhidrosis index were used as outcome measures to compare the efficacy of the two approaches. Patients' satisfaction and side effects were also evaluated. RESULTS: Of the 220 eligible patients, 60 underwent T3 sympathectomy (T3 group), and 160 underwent T3+T4 sympathectomy (T3+T4 group). Compared with the T3 group, the T3+T4 group showed higher symptom relief rates both for PAH (98.75% versus 93.33%, P = 0.048) and PLH (65.63% versus 46.67%, P = 0.01), and a greater postoperative decrease in both hyperhidrosis indices. The rate of severe compensatory hyperhidrosis also increased (10% versus 5%, P = 0.197), although the rates of overall satisfaction were comparable between the groups. The incidence of postoperative pneumothorax requiring chest tube placement and postoperative neuralgia was also similar. There were no cases of perioperative death, secondary operation, wound infection, or Horner syndrome in either group. CONCLUSIONS: Compared with T3 alone, T3+T4 sympathectomy achieved a higher symptom relief rate and a lower hyperhidrosis index. T3+T4 sympathectomy may be a choice for the treatment of concurrent PAH and PLH; however, patients need to be informed that this kind of surgery may increase the risk of compensatory sweating.

Does autonomic nervous system dysfunction influence cardiovascular disease risk in young adults with intellectual disability?

People with intellectual disability (ID) experience cardiometabolic-related morbidity and mortality. However, it has been suggested that this population presents and lives with underestimated cardiovascular risk factors at a younger age, hence affecting their overall health and quality of life and contributing to early mortality. We assessed autonomic nervous system function in subjects with ID (n = 39), aged 18-45 yr, through measures of sudomotor function, heart rate and systolic blood pressure variability, and cardiac baroreflex function. Traditional clinical cardiovascular measurements and a biochemical analysis were also undertaken. We found that young adults with ID presented with sudomotor dysfunction, impaired cardiac baroreflex sensitivity, and systolic blood pressure variability, when compared with age-matched control subjects (n = 38). Reduced hand and feet electrochemical skin conductance and asymmetry were significantly associated with having a moderate-profound ID. Autonomic dysfunction in individuals with ID persisted after controlling for age, sex, and other metabolic parameters. Subjects in the ID group also showed significantly increased blood pressure, body mass index, and waist/hip circumference ratio, as well as increased plasma hemoglobin A1c and high-sensitivity C-reactive protein levels. We conclude that autonomic dysfunction is present in young adults with ID and is more marked in those with more severe disability. These finding have important implications in developing preventative strategies to reduce the risk of cardiovascular disease in people with ID.NEW & NOTEWORTHY Adults with intellectual disability experience higher risk of premature death than the general population. Our investigation highlights increased cardiovascular risk markers and autonomic dysfunction in young adults with intellectual disability compared with control adults. Autonomic dysfunction was more marked in those with a more severe disability but independent of cardiovascular parameters. Assessment of autonomic nervous system (ANS) function may provide insight into the mechanisms of cardiometabolic disease development and progression in young adults with intellectual disability.

Disrupted local innervation results in less VIP expression in CF mice tissues.

Vasoactive Intestinal Peptide (VIP) is the major physiological agonist of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel activity. VIP functions as a neuromodulator and neurotransmitter secreted by neurons innervating all exocrine glands. VIP is also a potent vasodilator and bronchodilator that regulates exocrine gland secretions, contributing to local innate defense by stimulating the movement of water and chloride transport across intestinal and tracheobronchial epithelia. Previous human studies have shown that the rich intrinsic neuronal networks for VIP secretion around exocrine glands could be lost in tissues from patients with cystic fibrosis. Our research has since confirmed, in vitro and in vivo, the need for chronic VIP exposure to maintain functional CFTR chloride channels at the cell surface of airways and intestinal epithelium, as well as normal exocrine tissues morphology [1]. The goal of the present study was to examine changes in VIP in the lung, duodenum and sweat glands of 8- and 17-weeks old F508del/F508del mice and to investigate VIPergic innervation in the small intestine of CF mice, before important signs of the disease development. Our data show that a low amount of VIP is found in CF tissues prior to tissue damage. Moreover, we found a specific reduction in VIPergic and cholinergic innervation of the small intestine. The general innervation of the primary and secondary myenteric plexus was lost in CF tissues, with the presence of enlarged ganglionic cells in the tertiary layer. We propose that low amount of VIP in CF tissues is due to a reduction in VIPergic and cholinergic innervation and represents an early defect that constitutes an aggravating factor for CF disease progression.

Botulinum toxin: Pharmacology and injectable administration for the treatment of primary hyperhidrosis.

Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis.

Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining.

OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage.

Diagnostic utility of small fiber analysis in skin biopsies from children with chronic pain.

INTRODUCTION: Small fiber neuropathies (SFN) are associated with a reduction in quality of life. In adults, epidermal nerve fiber density (END) analysis is recommended for the diagnosis of SFN. In children, END assessment is not often performed. We analyzed small nerve fiber innervation to elucidate the potential diagnostic role of skin biopsies in young patients with pain. METHODS: Epidermal nerve fiber density and sudomotor neurite density (SND) were assessed in skin biopsies from 26 patients aged 7 to 20 years (15 female patients) with unexplained chronic pain. The results were compared with clinical data. RESULTS: Epidermal nerve fiber density was abnormal in 50% and borderline in 35% of patients. An underlying medical condition was found in 42% of patients, including metabolic, autoimmune, and genetic disorders. DISCUSSION: Reduction of epidermal nerve fibers can be associated with treatable conditions. Therefore, the analysis of END in children with pain may help to uncover a possible cause and guide potential treatment options.

Elimination of spurious absent sweat response in QSWEAT recordings.

INTRODUCTION: Forearm QSWEAT recordings are occasionally absent in females, likely due to high skin resistance. METHODS: We identified consecutive subjects with no sudomotor abnormalities but absent/markedly reduced QSWEAT forearm volume, and repeated QSWEAT at the same site after gentle abrasion. RESULTS: QSWEAT volumes were absent for 4 subjects and markedly reduced for the other 4 (median 0.01, IQR 0-0.03). After gentle skin abrasion, repeat volumes were significantly higher for all subjects and became normal in 7 of 8 subjects. DISCUSSION: Skin abrasion restores QSWEAT volumes in previously absent/markedly reduced site suggesting that skin preparation using abrasion is more effective.

The management of compensatory sweating after thoracic sympathectomy.

OBJECTIVE: The main therapeutic method of treatment for local hyperhidrosis is endoscopic thoracic sympathectomy. Generally, resections of the sympathetic trunk or ganglia are performed between the second rib and sixth rib. However, this procedure can result in compensatory sweating, in which excess sweating occurs on the back, chest, and abdomen. Compensatory sweating has been regarded as a thermoregulatory response and thought to be untreatable. This study suggests that compensatory sweating is not a physiologic reaction and is indeed treatable. METHODS: Eight patients with severe compensatory sweating were treated by observing blood perfusion of the skin with laser speckle flowgraphy, which determines the sympathetic nerves related to the area of skin with compensatory sweating. When intraoperative monitoring with laser speckle flowgraphy indicated the position of compensatory sweating by electrical stimulation of the sympathetic ganglion, ganglionectomy was performed. RESULTS: The skin domain that each sympathetic nerve controls was able to be detected by laser speckle flowgraphy. In all patients, compensatory sweating was resolved after interruption of the ganglia or sympathetic nerves related to compensatory sweating. CONCLUSIONS: Our results demonstrate that compensatory sweating is caused by denatured sympathetic nerves influenced by endoscopic thoracic sympathectomy and is not the result of a physiological response. With laser speckle flowgraphy, the sympathetic nerve related to the sweating of various parts of the body could be identified. The treatment of compensatory sweating on the back, chest, and stomach was previously considered to be difficult; however, compensatory sweating is demonstrated to be treatable with this technique.

Refined Quantitation of Sweat Gland Innervation.

Skin biopsies have gained increasing popularity as a tool to evaluate disorders affecting small nerve fibers. While reports on sweat gland nerve fiber density (SGNFD) to quantitate sudomotor innervation have been promising, methodologies vary significantly. Although conventional stereology is commonly used, no standard technique has been established. We sought to develop an accurate and reproducible technique to quantify SGNFD. Skin punch biopsies from healthy individuals were cut and stained. Images of sweat glands (SGs) were acquired using confocal and widefield microscopes, and optimized using deconvolution. Nerve fibers were reconstructed and nerve fiber length (NFL) was quantified using three-dimensional (3D) automated software. SGNFD was obtained by dividing NFL by SG volume. SGNFD was also assessed using stereology for comparison. Ninety-two SGs from 10 healthy subjects were analyzed by independent observers. Using confocal microscopy, the software reliably traced nerve fibers. In contrast, rendering of nerve fibers was inferior using widefield microscopy. Interobserver reliability was suboptimal using widefield images compared to confocal (ICC = 0.82 vs ICC = 0.98). Correlation between 3D-reconstruction and stereology was poor (ICC = 0.38). The newly developed technique of SGNFD quantitation using 3D reconstruction of SG innervation with confocal microscopy reliably traces nerve fibers, shows outstanding reproducibility, is almost completely unbiased, and superior to conventional stereology methods.

Association of small fiber neuropathy and post treatment Lyme disease syndrome.

OBJECTIVES: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. METHODS: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. RESULTS: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. CONCLUSIONS: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Needlescopic Video-Assisted Thoracic Bilateral T4 Sympathicotomy for the Treatment of Primary Palmar Hyperhidrosis: An Analysis of 200 Cases.

BACKGROUND: Primary palmar hyperhidrosis (PPH) is featured by aberrantly perspiration of the hands, which may bring a lot of inconvenience to patient's daily life and work. The purpose of this study is to summarize the clinical effect of needlescopic video-assisted thoracic bilateral T4 sympathicotomy for the treatment of PPH. PATIENTS AND METHODS: Between January 2009 and March 2014, 200 patients received needlescopic video-assisted thoracic bilateral T4 sympathicotomy. We, respectively, took two 5-mm incisions in the third intercostal space on the anterior axillary line and in the fifth intercostal space on the middle axillary line. After collapsing left lung, needlescopic exploration was the first step to determine the targeted sympathetic chain through the third intercostal space. Electric coagulation hook was inserted from another port to cut T4 sympathetic chain and the bypassing nerve fibers for 2 to 3 cm along the surface of the fourth rib. Right thoracic cavity was also administered the same procedure. The palmar temperature was recorded before and after sympathicotomy. The symptom improvement, operative complications, patients' recovery, and satisfaction were evaluated. FINDING: One hundred and ninety-seven patients uneventfully received two 5-mm port bilateral sympathicotomy, and another 3 patients with extensive pleural adhesions completed the surgery through enlarging the third intercostal incision to 2 cm without conversion to open surgery. All operative procedures were completed in 15 to 35 minutes. The hospital stay was 2 to 4 days. The palmar temperature increased by 2.0 ± 0.5°C, and hyperhidrosis immediately disappeared in both hands after surgery. The efficacy rate was 100%. The postoperative complications such as hemorrhage, hemopneumothorax, bradycardia, or Horner's syndrome had no occurrence. During 6 to 60 months follow-up, mild compensatory sweating of buttock, back, and thigh occurred in 30 patients (15%) at 2 to 5 days after surgery and gradually disappeared at postoperative 15 to 30 days or longer time. All patients were greatly satisfied with the effect with better confidence and quality of life. Until now, no recurrent palmar hyperhidrosis happened. CONCLUSION: Needlescopic video-assisted thoracic bilateral T4 sympathicotomy could reach an excellent and immediate result of treating PPH. It is a safe, convenient, and minimally invasive method appropriate for wide clinical use.

Evaluation of Quality of Life: Functional Assessment of Chronic Illness Therapy after Thoracic Sympathectomy for Palmar Hyperhidrosis.

BACKGROUND: Primary hyperhidrosis is a condition that significantly decreases the quality of life (QOL). Thoracic sympathectomy is safe and efficient method of treatment in palmar hyperhidrosis. OBJECTIVE: The aim of the study was to evaluate the change in QOL in patients with palmar hyperhidrosis who underwent thoracic sympathectomy. METHODS: The study includes 149 patients (37 men and 112 women) who were treated with bilateral thoracoscopic sympathectomy for primary palmar hyperhidrosis. Subjective and objective evaluation of hyperhidrosis were performed prior to the surgery, 3 and 12 months after the treatment. Control group consists of 305 healthy volunteers (118 men and 187 women). The QOL was measured using Functional Assessment of Chronic Illness Therapy (FACIT) scale. RESULTS: The average level of palmar hyperhidrosis in the study group prior to surgery was 224.69 ± 179.20 mg/min/m2. General QOL (FACIT total) before the surgery was significantly lower in the study group when compared with the control group (66.57 ± 16.33 vs. 91.29 ± 11.13; p < 0.05). Three months after surgery level of hyperhidrosis decreased significantly and remained at similar level 12 months after the procedure (13.55 ± 15.41 mg/min/m2 p < 0.05 and 14.41 ± 18.19 mg/min/m2 p < 0.05, respectively). After thoracoscopic sympathectomy, the QOL increased and did not differ when compared with the control group 3 and 12 months after the surgery (90.28 ± 11.13 vs. 91.29 ± 11.13; p = 0.55 and 89.59 ± 11.34 vs. 91.29 ± 11.13; p = 0.84, respectively). The highest increase was observed in functional well-being domain (32.25%); however, it was also noticeable in other domains. CONCLUSION: Thoracic sympathectomy is an efficient method of treatment in palmar hyperhidrosis which significantly increases patients' QOL especially in a functional domain.

Efficacy of Miniuniportal Video-Assisted Thoracoscopic Selective Sympathectomy (Ramicotomy) for the Treatment of Severe Palmar and Axillar Hyperhidrosis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) clipping of the sympathetic branch has become the standard approach for the treatment of essential hyperhidrosis when conservative treatment failed. However, this is associated with relevant potential complications such as postoperative compensatory sweating and recurrent sweating. We report the outcome after selective sympathectomy (ramicotomy) through a miniuniportal VATS approach in patients with therapy-refractory palmar and/or axillary hyperhidrosis. METHODS: A total of 51 consecutive patients (37 females, mean age: 30 years, range: 12-64 years) who suffered from therapy-refractory palmar and/or axillary severe hyperhidrosis were included. Data were prospectively collected and retrospectively analyzed. All patients underwent bilateral miniuniportal VATS ramicotomy. Duration of surgery, hospital stay, recurrent, and compensatory sweating were documented. RESULTS: All patients had palmar sweating, where 51% had additional axillary sweating and 57% had additional plantar sweating. In all patients, selective division of the rami communicantes of the thoracic sympathetic ganglions Th2 to Th5 was performed. The mean duration of bilateral surgery for both sides was 67 ± 2.5 minutes. The mean postoperative hospital stay was 2 ± 1 days. After surgery and at further follow-up (mean: 12 ± 2.5 months), all patients presented dry and warm hands and axillae, without any evidence of compensatory or recurrent sweating. All patients described a remarkable increase in quality of life. CONCLUSION: Miniuniportal VATS ramicotomy represents a feasible surgical technique with a very high success and satisfaction rate. Therefore, this approach should be considered as the method of choice for the treatment of patients with severe therapy-refractory palmar and axillary hyperhidrosis.

Six-Month Comparative Analysis Monitoring the Progression of the Largest Diameter of the Sweating Inhibition Halo of Different Botulinum Toxins Type-A.

BACKGROUND: Excessive sweating is a clinical condition that can be improved with type-A botulinum toxin (BTX-A). OBJECTIVES: To evaluate and compare the largest diameter of sweating inhibition halo (SIH) of 5 different commercially available BTX-A, in five different doses, in a 6-month-long clinical evaluation. METHODS: Twenty-five adult female volunteers were injected in the dorsal trunk area with both 100 units (100UI) and 500 units (500UI) BTX-A products, reconstituted in a ratio of 1:2.5 IU, respectively. Products were applied in five different concentrations (1:2.5U, 2:5U, 3:7.5U, 4:10U, and 5:12.5U). After 30, 60, 90, 120, 150, and 180 days, a starch-iodine test was performed to obtain the largest diameter of each SIH. RESULTS: The higher the number of units used, the larger the SIH p < 0.05 for all BTX-A. However, Botox®, Botulift®, Dysport®, and Prosigne® have pretty likewise SIH along the study, with some few differences for some doses and months between one and another. However, Xeomin® is the BTX-A with the smallest SIH, in comparison with all others, in any dose and period. CONCLUSIONS: Differences were observed among all brands of BTX-As, based on dose and time after injection. Xeomin® provides the smallest SIH in comparison with others BTX-A.