Psychiatric profile and quality of life of subjects with excess weight treated with transcranial direct current stimulation combined with a hypocaloric diet.

Background: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) may reduce appetite and caloric intake and may be able to play a role as an adjunct treatment for obesity. Stimulation of this brain area is also used for the treatment of depression, which shares a common pathophysiology with obesity. As a result, the effect of tDCS on mental health and its impact on the quality of life of subjects with excess weight needs to be addressed.Objective: To assess the effect of daily tDCS of the right DLPFC on mood, daytime sleepiness, anxiety and quality of life in subjects with excess weight on a hypocaloric diet.Methods: We randomly assigned 28 subjects to receive 20 sessions of active or sham tDCS over the right DLPFC for 20 consecutive weekdays. The severity of depressive and anxiety symptoms was assessed by the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory-State (STAI-S). Sleepiness was measured by a daytime sleepiness questionnaire (DSQ), and quality of life was measured by the 36-Item Short Form Health Survey (SF-36).Results: There were no significant changes in BDI, STAI-S and DSQ scores between groups, even after adjustments for the use of antidepressant medications and changes in body weight. There were also no significant changes in different subscales of the SF-36 quality of life questionnaire between groups.Conclusion: Repetitive tDCS on the right DLPFC is not associated with impairment in mental health or quality of life in overweight and obese subjects.

Progression rate of myelopathy in X-linked adrenoleukodystrophy heterozygotes.

X-linked adrenoleukodystrophy heterozygote women can present adult onset myeloneuropathy and little is known about its natural history. We aimed to describe the progression rate of the neurological impairment in the prospective follow-up of our cohort and to look for prognostic factors. The neurological scales Japanese Orthopaedic Association (JOA) and Severity Score System for Progressive Myelopathy (SSPROM) were applied at baseline in 29 symptomatic carriers and in follow-up visits. Age at onset, disease duration, X inactivation pattern, determination of the allele expressed, plasma levels of the very long chain fatty acids and of the neuron-specific enolase, and somato-sensory evoked potentials, were taken at baseline. The slope of the linear regression of both JOA and SSPROM versus disease duration since the first symptom was estimated using mixed modeling. JOA and SSPROM decreased 0.42 and 1.87 points per year, respectively (p < 0.001). None of the parameters under study influenced these rates. We estimated that the number of carriers per arm needed in a future 12 month trial with 80% power and a 50% reduction in disease progression would be 225 women for JOA and 750 for SSPROM. The progression rates of the studied neurological scales were small, did not depend on any modifier factor known, and reflected the characteristically slow worsening of symptoms in X-ALD heterozygotes. Better biomarkers are still necessary for future studies.

Abnormal modulation of electrodermal activity by thermoalgesic stimuli in patients with primary palmar hyperhidrosis.

BACKGROUND: The authors examined the effects of thermal stimulation on electrodermal activity (EDA) in patients with primary palmar hyperhidrosis (PPH). The authors hypothesised that temperature changes may induce abnormal sudomotor reactions because of simultaneous activation of sudomotor centres through thermal and emotional pathways, and compared patients before and after thoracoscopic sympathectomy. METHODS: The authors studied 18 PPH patients and 20 controls. Patients reported subjective evaluation of their symptoms using a visual analogue scale for palmar sweating and for body sweating (bs-VAS). The authors applied focal thermal stimulation to quantify sensory perception and measure ongoing changes in EDA recorded from the palm of the hands. RESULTS: Before sympathectomy, patients had lower sensory perception thresholds and higher EDA levels than controls. Increased EDA occurred along the whole test, with no significant modulation by changes in thermal stimulation. Sensory perception normalised after sympathectomy, but thermal modulation of EDA remained abnormal whenever sudomotor activity was present after surgery. There was a significant positive correlation between EDA levels before treatment and the bs-VAS (from r=0.45 to r=0.57). CONCLUSIONS: Patients with PPH show perceptual abnormalities and exaggerated sudomotor reactions to thermoalgesic stimulation, consistent with central sensitisation of sympathetic circuits. The reduced sympathetic outflow after thoracoscopic sympathectomy induced normalisation of sensory perception, but it did not modify the abnormal control of efferent sudomotor activity.

Brazilian Portuguese validation of the Leeds Assessment of Neuropathic Symptoms and Signs for patients with chronic pain.

BACKGROUND: Neuropathic pain (NP) is a very frequent and unrecognized condition in clinical practice. Therefore, it is important to have a reliable instrument to assess pain subtypes in various cultures. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) has been widely used and validated in many countries. Up to now, there has been no reliability study of this instrument in Brazil. METHODS: The scores of the Brazilian Portuguese version of the LANSS were studied in a sample of 90 chronic pain outpatients from southern Brazil. LANSS was translated into Portuguese and then back translated to English. Intraclass correlation coefficient (ICC) and internal consistency (IC) were estimated. The intensity of pain complaints, other demographic data, and LANSS scores distribution according to pain subtypes (nociceptive, neuropathic, and mixed) were also evaluated. RESULTS: The Brazilian Portuguese version of the LANSS showed good ICC (r = 0.97) and IC (Cronbach's α = 0.67 for total LANSS score). Patients with NP provided significant higher LANSS scores (19.1 ± 3.3) in comparison with those with nociceptive (7.3 ± 4.5) and mixed (13.9 ± 3.7) types of pain. CONCLUSIONS: This LANSS version was found to be a reliable instrument for the evaluation of pain complaints due to a variety of causes. The profile of pain scores was similar to that observed in other countries.

The effect of transcranial direct current stimulation along with a hypocaloric diet on weight loss in excessive weight people: A pilot randomized clinical trial.

BACKGROUND & AIMS: The dorsolateral prefrontal cortex plays an important role in the desire to eat and food intake regulation and may be a target for transcranial direct current stimulation (tDCS) to promote weight loss. Our aim was to test the effect of repeated, active tDCS along with a hypocaloric diet (HD) on weight loss in overweight adults. METHODS: This was a randomized, placebo-controlled, double-blind pilot study conducted in Porto Alegre, Brazil. Twenty-eight overweight adults were selected to receive 4-week (20 sessions, t0 to t20; 5 weekdays) fixed-dose tDCS along with an HD. Subjects were randomly assigned to active (AG) or sham (SG) tDCS groups. The primary outcome was weight loss as determined via body weight measurements at baseline (t0), weekly (t5, t10, t15, and t20), and after the intervention (tF). A visual analogue scale was used to assess desire to eat at t0 and at tF. Registered under ClinicalTrials.gov Identifier no. NCT02683902. RESULTS: Although there was a greater weight loss in the AG (mean -4.5 kg [95%CI: -9.4, 0.5]) than in the SG (-2.3 kg [-5.0, 0.3]), this difference was not statistically significant. However, the AG showed a significant reduction in the desire for sweet foods (P = 0.005). CONCLUSIONS: Although this pilot study did not show that repeated tDCS is able to optimize weight loss, it was able to reduce the desire to eat sweet foods. These findings suggest that a protocol with a larger sample size could determine whether tDCS may be an adjunctive treatment of obesity.

Sympathetic skin responses evoked by different stimuli modalities in spinal cord injury patients.

OBJECTIVE: By using a combination of physiological and electrical peripheral nerve stimuli, the authors aimed to characterize the expected dysfunction of the circuits responsible for sympathetic skin response (SSR) in persons with spinal cord injury (SCI). METHODS: The authors examined SSR induced in the hand and foot in 50 SCI patients and 15 age-matched and gender-matched healthy volunteers. SSR was induced by deep inhalation, unexpected acoustic stimuli, brisk hand muscle contraction, and median and peroneal nerve electrical stimulation (PNS). RESULTS: SSRs to any stimulus modality were absent in hand and foot in patients with complete SCI above the T4 level. They were present in the hand and absent in the foot in complete SCI patients at levels between T4 and T11 for all stimuli modalities except PNS. The elicitability of SSR was lower with peroneal nerve stimulation than the other stimuli in hand and foot. The mean latency difference between SSRs of the hand and foot was significantly longer in patients than in controls, regardless of stimulus modality. The amplitude of SSR was larger in volunteers than in patients. CONCLUSION: SSR to various stimuli confirms the importance of supraspinal centers and the integrity of sympathetic descending pathways. Simultaneous recording of the SSR in the hands and feet provides information about the degree of sympathetic impairment possibly in the efferent pathway. To monitor spontaneous recovery or the efficacy of a drug or biological therapeutic intervention, changes in the latency delay between the hand and foot may be valuable.

Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP).

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

Effect of transcranial direct current stimulation associated with hypocaloric diet on weight loss and metabolic profile in overweight or obesity: study protocol for a double-blind, randomized controlled clinical trial.

BACKGROUND: Dietary interventions have limited success in promoting sustainable weight loss; new treatments allowing better compliance with hypocaloric diets should be developed. The aim of this trial is to describe the effects of a protocol combining repetitive active transcranial direct current stimulation (tDCS) with a hypocaloric diet on weight loss and food consumption in overweight or obese adults. METHODS/DESIGN: Overweight or obese adults between 20 and 50 years of age with stable weight over the last 4 months will be selected for a 4-week randomized clinical trial of fixed-dose tDCS (20 sessions; 5 consecutive weekdays/wk, 2 mA, 20 minutes) over the right dorsolateral prefrontal cortex associated with a weight loss diet. The subjects will be randomly assigned in a 1:1 ratio and stratified by sex to active tDCS + diet or sham tDCS + diet. The study will be conducted at the Endocrine and Metabolism Unit of the Hospital de Clínicas de Porto Alegre, Brazil. The primary outcome is weight loss. Energy and macronutrient consumption, as well as adherence to the diet, will be assessed using 3-day weighed dietary records. Changes in blood glucose and plasma insulin will be assessed, and participants will complete self-report questionnaires to assess changes in mood and food behavior. All analyses will be done on a per-protocol and intention-to-treat basis. DISCUSSION: This study explores the potential role of tDCS as an adjunctive treatment with a hypocaloric diet for obesity management. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02683902 . Registered on 11 January 2016.

Definition and diagnosis of small fiber neuropathy: consensus from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology.

The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN). Fifteen neurologists (members of the Brazilian Academy of Neurology) reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus) or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.

A double-blind, randomized, crossover study of prosigne versus botox in patients with blepharospasm and hemifacial spasm.

There is a lack of evidence on the clinical efficacy and safety of the recently released Chinese botulinum toxin serotype A (Prosigne) for the treatment of focal dystonias and hemifacial spasm. Determining a more precise role of Prosigne in the treatment of such conditions is of paramount importance, because botulinum toxin type A treatments have a huge economic implication in health services, especially in developing countries. The aim of our study was to compare the efficacy and safety of Prosigne in the treatment of blepharospasm and hemifacial spasm in comparison to Botox. We performed a double-blind, randomized, crossover study enrolling 26 patients. There were no significant differences between Prosigne and Botox regarding subjective global improvement, response onset, efficacy duration, and incidence and severity of adverse events. Our results suggest that Prosigne and Botox are comparable with respect to efficacy and safety for the short-term treatment of blepharospasm and hemifacial spasm.

Transcranial direct current stimulation effects on menopausal vasomotor symptoms.

OBJECTIVE: To assess the effects of transcranial direct current stimulation (tDCS) compared with tDCS-sham on vasomotor symptoms of postmenopausal women. METHODS: Postmenopausal women (N = 30), aged between 45 and 68 years, with at least four episodes of vasomotor symptoms per day, were recruited from a specialized outpatient clinic at a tertiary hospital in the south of Brazil and through a media call after inclusion and exclusion criteria were ensured. Active and tDCS-sham were administered over the motor cortex position (anode electrode) and contralateral supraorbital region (cathode electrode) for 10 consecutive days, except weekends. The number and intensity records of hot flashes were evaluated for 7 days before and along 30 days after the intervention. The Women's Health Questionnaire and the Hamilton Depression Rating Scale were applied to assess the quality of life and the depressive symptoms, respectively. RESULTS: The frequencies of hot flashes per day happened in a similar way in both groups, with a reduction in the first 3 weeks after the intervention. There was a return in hot flash frequencies to baseline in the fourth week (week 0: 79.0 ±â€Š6.2 and 75.8 ±â€Š6.0, week 1: 61.6 ±â€Š9.6 and 57.0 ±â€Š7.8, week 2: 56.8 ±â€Š8.9 and 55.9 ±â€Š7.1, week 3: 56.8 ±â€Š8.9 and 54.2 ±â€Š7.2, week 4: 64.9 ±â€Š10.7, 70.1 ±â€Š8.9; tDCS-sham and tDCS groups, respectively). In the tDCS group, a trend towards a conversion of intensive hot flashes into mild ones was observed. CONCLUSIONS: Our results suggest that the tDCS technique showed small trends on postmenopausal vasomotor symptoms, justifying searches for more effective methods by which tDCS could reduce hot flashes.

Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998.

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998. Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment. Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were implemented. Results: Fifteen articles met our criteria. The majority were small-randomized controlled clinical trials that enrolled a mean of approximately 26 subjects (Phase II studies). Most of the studies (around 83%) assessed the role of tDCS in the treatment of psychiatric conditions, in which the main outcomes were measured by means of behavioral scales and clinical observation, but the diagnostic precision and the quality of outcome monitoring, including adverse events, were deficient by modern standards. Compared to modern tDCS dose, the stimulation intensities used (0.1-1 mA) were lower, however as the electrodes were typically smaller (e.g., 1.26 cm2), the average electrode current density (0.2 mA/cm2) was approximately 4× higher. The number of sessions ranged from one to 120 (median 14). Notably, the stimulation session durations of several minutes to 11 h (median 4.5 h) could markedly exceed modern tDCS protocols. Twelve studies out of 15 showed positive results. Only mild side effects were reported, with headache and skin alterations the most common. Conclusion: Most of the studies identified were for psychiatric indications, especially in patients with depression and/or schizophrenia and majority indicated some positive results. Variability in outcome is noted across trials and within trials across subjects, but overall results were reported as encouraging, and consistent with modern efforts, given some responders and mild side effects. The significant difference with modern dose, low current with smaller electrode size and interestingly much longer stimulation duration may worth considering.

Positive effects of transcranial direct current stimulation in adult patients with attention-deficit/hyperactivity disorder - A pilot randomized controlled study.

Almost 30% of adult patients with attention-deficit/hyperactivity disorder (ADHD) do not respond or tolerate standard pharmacological interventions. Few clinical investigations addressed the efficacy and tolerability of transcranial direct current stimulation (tDCS), a non-invasive neuromodulatory technique, in the disorder. We performed a double-blind, sham-controlled randomized clinical trial in 17 patients with ADHD. The set up for tDCS was the following: 2mA/20min/day for 5 days with the anode over the right dorsolateral prefrontal cortex and cathode over the left dorsolateral prefrontal cortex. ADHD symptoms were measured by the Adult ADHD Self-Report Scale (ASRS) and impairment with the Sheehan Disability Scale (SDS) in four different time points after stimulation. Participants achieved significant lower ASRS inattention and SDS scores after active tDCS in comparison with sham stimulation group. In addition, we detected a trend for a lower ASRS total score in the active tDCS group. Follow up data analysis revealed a positive interaction between time and treatment in both ASRS inattention, SDS and ASRS total scores. Short-term application of tDCS in adult patients with ADHD improved their symptoms, and this improvement persisted after the end of the stimulation. Future studies with larger sample sizes are needed.

Evaluation of sympathetic skin response in Parkinson's disease.

There is no clear definition on the role of sympathetic skin response (SSR) in the evaluation of patients with Parkinson's disease (PD). We recorded the SSR of the palms of 64 controls and 46 patients with PD to electrical stimulation of the median nerve at the wrist. We analyzed onset latency and peak-to-peak amplitude. A study of parasympathetic function (R-R interval analysis) was also undertaken. We found that patients with PD had more absent SSRs than controls. The mean amplitude of the SSR was significantly reduced in both lower and upper limbs of PD patients in comparison with control subjects (p<0.001). The onset latency was longer in the lower limbs of these patients in respect to the control group (p<0.003). There was a significant inverse correlation between SSR amplitudes and age, severity and late onset of the disease. There was no association of these parameters with dysautonomic symptoms or R-R interval variation. In conclusion, there is a significant association between altered SSR and PD and an inverse correlation in this group of patients between SSR values and older age, greater severity and later onset of disease. Therefore, the study of SSR may provide valuable information on cholinergic sympathetic function in patients with PD.

Quality of life in a Brazilian sample of patients with Parkinson's disease and their caregivers.

OBJECTIVE: Parkinson's disease is a common neurodegenerative disorder characterized by motor disabilities and increasing dependence on others for daily life activities with consequent impact on patients' and caregivers' quality of life. METHOD: A cross-sectional study was performed in which quality of life was assessed by the WHOQOL-BREF questionnaire in 21 patients with Parkinson's disease and their respective caregivers. RESULTS: Significant differences between patients and caregivers were found in physical (p < 0.001) and psychological (p = 0.002) domains. In the Parkinson's disease group there was a significant inverse correlation between the psychological domain and duration of disease (p = 0.01), as well as between social domain and severity of disease (p = 0.001). There was a positive correlation between physical domain scores and number of people living in the same house (p = 0.02). The only significant finding in the group of caregivers was an inverse correlation between the social domain and the patients' age (p = 0.04). CONCLUSION: Duration, severity of the disease and the number of people living in the same house were the most important predictors of quality of life of Parkinson's disease patients. The age of the patients was the only significant predictor found in the caregivers' quality of life. In order to complement our findings, further short-form questionnaires should be validated for Brazilian samples of Parkinson's disease.

Simultaneous Median-Radial Nerve Electrical Stimulation Revisited: An Accurate Approach to Carpal Tunnel Syndrome Diagnosis and Severity.

PURPOSE: To assess the accuracy of an unusual test for CTS investigation and correlate it with clinical symptoms. METHODS: Initially, we applied a visual analog scale for CTS discomfort (CTS-VAS) and performed a standard electrophysiologic test for CTS diagnosis (median-ulnar velocity comparison). Posteriorly, a blinded neurophysiologist performed the orthodromic simultaneous median-radial nerve stimulation (SMRS) at the thumb, with recording of both action potentials over the lateral aspect of the wrist. RESULTS: All hands (106) showed median-radial action potential splitting using the SMRS technique, in which was possible to measure the interpeak latencies (IPLs) between action potentials. The IPL and median nerve conduction velocity were different according to CTS intensity (Bonferroni; P < 0.001). There was significant correlation between IPL and median nerve conduction velocity (Spearman; r = -0.51; P < 0.01). In the same way, there was a significant correlation between IPL and median nerve conduction velocity with CTS-VAS (r = 0.6 and r = -0.3, respectively). The duration and unpleasantness of the SMRS procedure were lower when compared with standard approach (t Student < 0.001 for both comparisons). Twenty-nine symptomatic patients (39 hands) who did not fulfill criteria for CTS based on standard approach showed abnormal IPLs. CONCLUSIONS: The SMRS technique is a simple, sensitive, and tolerable approach for CTS diagnosis. Apart from that, the data from SMRS correlated better with clinical impact of CTS in comparison with the standard approach. Therefore, this method might be useful as adjunct to standard electrophysiologic approaches in clinical practice.

S100B and NSE serum levels in patients with Parkinson's disease.

We evaluated S100B protein and neuron-specific enolase (NSE) serum levels in Parkinson's disease (PD) patients and their correlation with the severity of disease. The levels of S100B (P=0.16) and NSE (P=0.39) between PD and controls were similar. However, S100B levels correlated positively with the Hoehn and Yahr scale (r=0.368; P=0.02) and negatively with the Activities of Daily Living (ADL) scale (r=-0.431; P=0.006). Therefore, S100B and NSE may not have a diagnostic role in PD, but S100B may have a potential role as a marker of disease progression. The study of S100B may also contribute to elucidate the controversial role of glial cells in PD.

Functional and regenerative effects of local administration of autologous mononuclear bone marrow cells combined with silicone conduit on transected femoral nerve of rabbits.

The inoculation of cells into injury sites can accelerate and improve the quality of nerve regeneration. This study aimed to evaluate the functional and regenerative effects of mononuclear autologous bone marrow cells (MABMC) combined with silicon conduit grafting in rabbit femoral nerves. Twenty-eight animals were allocated to one of two groups: treatment group (TG) or control group (CG), divided according to the time of evaluation, at either 50 or 75 days. After neurotmesis of the femoral nerve, surgical repair was performed with nerve autografts in silicon conduits, leaving a 5mm gap in both groups. The TG received MABMC in silicon conduits, and CG received a sham saline inoculum. Histological, clinical and electrophysiological analyses detected no differences between groups, but analysis of leg diameter showed that TG diameters were larger. This cell therapy did not improve regeneration of the femoral nerve, but there was a tendency for better functional recovery.