Sympathetic Skin Response Research Articles

Effect of aging on cardiovascular responses to cold stress in humans

Abstract Cold exposure increases the risk of adverse events related to cardiovascular causes, especially in the elderly. In this review, we focus on recent findings concerning the impact of aging on the regulatory mechanisms of cold-induced cardiovascular responses. In response to cold exposure, the initial physiological thermoregulation in healthy young persons, such as cutaneous vasoconstriction to reduce heat loss, is attenuated in older individuals, resulting in a reduced ability of the older persons to maintain body temperature in cold environment. Impaired sympathetic skin response, reduced noradrenergic neurotransmitter synthesis, insufficient noradrenergic transmitters, and altered downstream signaling pathways inside the vascular smooth muscle may be among the underlying mechanisms for the maladaptive vasoconstrictive response to cold stress in the elderly. The increase in blood pressure during cold exposure in young persons may be further augmented in aging adults, due to greater central arterial stiffness or diminished baroreflex sensitivity with aging. Cold stress raises myocardial oxygen demand caused by increased afterload in both young and old adults. The elderly cannot adjust to meet the increased oxygen demand due to reduced left ventricular compliance and coronary blood flow with advancing age, rendering the elderly more susceptible to hypothermia-induced cardiovascular complications from cold-related diseases. These age-associated thermoregulatory impairments may further worsen patients' health risk with existing cardiovascular diseases such as hypertension, coronary artery disease, and heart failure. We searched PubMed for papers related to cold stress and its relationship with aging, and selected the most relevant publications for discussion.

Stereological and electrophysiological evaluation of autonomic involvement in amyotrophic lateral sclerosis

ObjectivePrevious studies have identified autonomic dysfunction in amyotrophic lateral sclerosis (ALS) using mostly neurophysiological techniques. In this study, stereological evaluation of autonomic fibers and sweat glands has been performed to identify structural evidence of autonomic denervation in patients with ALS. MethodsIn this study, 29 ALS patients were compared to 29 controls using COMPASS-31 questionnaire, sympathetic skin response (SSR), and heart rate variability (HRV) at rest. From the same cohorts, 20 ALS patients and 15 controls were further evaluated using staining of autonomic nerve fibers and sweat glands in skin biopsies. SSR and resting HRV were repeated in the ALS patient cohort one year later. ResultsCOMPASS-31 total score, gastrointestinal- and urinary-sub scores were higher in ALS patients than controls (P = 0.004, P = 0.005, and P = 0.049, respectively). In the ALS patient cohort, SSR amplitudes in hands and feet were lower than in controls (P<0.0001 and P = 0.0009, respectively), but there was no difference in resting HRV (P>0.05). While there was no change in nerve fibers innervating sweat glands, their density was lower in ALS patients than controls, and semi-quantitative analysis also showed structural damage (P = 0.02 and P = 0.001, respectively). SSR and resting HRV of ALS patients remained stable during the one-year follow-up period (P>0.05). DiscussionSupporting abnormal neurophysiological tests, stereological analysis revealed direct evidence of autonomic denervation in ALS patients. However, the degenerative process in autonomic nerve fibers is relatively slow, compared to the rate of motor neuron degeneration in this condition.

Skin temperature response to thermal stimulus in patients with hyperhidrosis: A comparative study

Primary hyperhidrosis (HH), the excessive sweating exceeding physiological demand, has been associated to a complex dysfunction of the autonomic nervous system which may explain the disfunction in sweating but may also cause unrevealed alterations in skin blood flow regulation. In fact, HH patients present a sympathetic over-function with less reflex bradycardia in response to the Valsalva maneuver and higher sympathetic skin responses. We aimed to identify response patterns to room thermal stimulus in HH patients compared to a control group in order to investigate putative differences in blood flow assuming that skin temperature in glabrous (non-hairy) areas reflect the sympathetic tone in arteriovenous anastomoses (AVAs). Infrared thermography images were obtained from a cohort of patients diagnosed with HH, followed at a hospital pediatric surgical department and to a sex- and age-matched control group of patients admitted for other surgical procedures. With the participants in Fowler's position, a set of 3 images were captured simultaneously and 44 regions of interest were analyzed, distributed on the palms of the hands, soles of the feet, axilla, and inner canthus. After an acclimatization period at 20 °C, the room temperature was increased to 24, 28 and 32 °C to obtain similar sets of thermograms. A total of 37 patients with HH and 16 participants in the control group were included in the study. At baseline (20 °C), body core temperature (measured in the inner canthus) was significantly higher in the HH patients compared to the controls (p = 0.019 and p = 0.003 in right and left inner canthi, respectively), without any significant differences in the other thermograms. When room temperature was increased, differences in core temperature disappeared, while differences appeared in axilla and palms of the hands with HH patients presenting significantly lower temperature at the three thermal stimulus stages. Patients with HH presented a lower thermoregulatory response when submitted to room temperature increase, which may reflect a vasomotor sympathetic over-function in AVAs.

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury.

Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. Enhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p= 0.009) and HC (-59%, p= 0.021). In contrast, no group differences were found (p= 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r= 0.561, p= 0.024; body regions: r= 0.564, p= 0.023). These results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective.

PurposeHere , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.MethodsStep 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis.ResultsThere were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate.ConclusionNeuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.

Evaluation of Neuromuscular Functions in Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis is the most prevalent autoimmune thyroid disease with an increasing incidence. Although the exact causes and pathogenesis of Hashimoto’s thyroiditis are not yet fully understood, the literature indicates complex interactions of immunologic, genetic, environmental, and epigenetic factors. It generally leads to hypothyroidism which can cause neuromuscular problems including neuropathy and myopathy. Data on neuromuscular functions of Hashimoto’s thyroiditis patients are relatively underreported and not up to date.The current observational study aimed to evaluate neuromuscular functions and sympathetic skin responses (SSR) in patients with Hashimoto’s thyroiditis and compare them with healthy participants. In total, 50 patients (25 females, 25 males; mean age, 31.6±4.9 years; range: 25-40 years) including 33 euthyroid, 10 with subclinical hypothyroidism, and 7 with hypothyroidism were included. The control group consisted of 50 healthy individuals (25 females, 25 males; mean age: 31.5±5.1 years; range, 25-40 years). Nerve conduction studies, repetitive nerve stimulation, SSRs and F wave recordings were performed in all participants. There were significant differences in the mean SSR latency and amplitude both in the upper extremities (p&amp;lt;0.001 and p=0.013, respectively) and in the lower extremities (p=0.008 and p=0.002, respectively) in the comparison groups. There was a significant difference in comparison groups regarding needle electroneuromyography (EMG) tests (p=0.012) and 14% of the patients showed myogenic EMG findings. In addition, a significant correlation was found between EMG findings and anti-TPO levels in the Hashimoto’s thyroiditis patients (r=0.453; p=0.001). No significant differences were found in the nerve conduction studies, routine EMG tests, repetitive nerve stimulations or F wave recordings between patients and control groups. Hashimoto’s thyroiditis, can cause negative influences on the proper functioning of neuromuscular systems. SSR, and electrophysiological tests may be beneficial for early detection and investigation of neuromuscular abnormalities in these patients.

Cardiomyopathy correlates to nerve damage in p.A117Slate‐onset transthyretin amyloid polyneuropathy

ObjectiveLate‐onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is often associated with heart involvement. Recent advances in cardiac imaging allow the detection of cardiac amyloidosis. This study aimed to explore cardiomyopathy by cardiac imaging and its clinical correlates with polyneuropathy in late‐onset ATTRv‐PN.MethodsPolyneuropathy was assessed by intraepidermal nerve fiber (IENF) density, nerve conduction study (NCS), autonomic function tests, quantitative sensory testing, and clinical questionnaires. Cardiomyopathy was evaluated by echocardiography, 99mTc‐pyrophosphate (PYP) single‐photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum Pro‐B‐type natriuretic peptide. Healthy controls and patients with Brugada syndrome were enrolled for comparison of CMR.ResultsFifty late‐onset ATTRv‐PN patients (38 men, 46 with p. A117S mutation), aged 63.7 ± 5.5 years, of polyneuropathy disability stage 1–4 were enrolled. All patients presented polyneuropathy in NCS, and 74.5% of patients had reduced IENF density in distal legs. All patients showed significant radiotracer uptake in the heart on 99mTc‐PYP SPECT imaging, and 87.8% of patients had abnormally increased left ventricular (LV) septum thickness on echocardiography. CMR showed longer myocardial native T1, larger extracellular volume, greater LV mass index, and higher LV mass to end‐diastolic volume ratio in ATTRv‐PN patients than healthy controls and patients with Brugada syndrome. These CMR parameters were associated with skin denervation, absent sympathetic skin responses, elevated thermal thresholds, worsened NCS profiles, and functional deficits of polyneuropathy.InterpretationLate‐onset ATTRv‐PN coexisted with cardiomyopathy regardless of the clinical severity of polyneuropathy. The cardiac amyloid burden revealed by CMR was correlated with pathophysiology and clinical disability of nerve degeneration.

A Temporospatial Study of Sympathetic Skin Response and Electroencephalogram in Oral Mucosa Thermal Perception.

ObjectiveTo investigate the temporospatial changes in sympathetic skin response (SSR) and electroencephalogram (EEG) under thermal stimuli and to draw a topographic map of SSR threshold temperature of the oral mucosa.Materials and MethodsA total of 40 healthy volunteers (24 men, 16 women, mean age of 23 ± 3) were enrolled. Thermal stimuli were applied to the 35 partitions of oral mucosa starting from 36°C at the gradience of 1°C and the lowest temperature evoked SSR was defined as SSR threshold temperature. SSR and EEG signals at 45, 48, 51, and 54°C were then recorded synchronously.ResultsThe SSR threshold temperature increased from the anterior areas to the posterior areas. No significant difference between bilateral corresponding areas or between genders was observed. The SSR amplitude value increased from 45 to 54°C in the same area, while the highest value was recorded on the tip of the tongue and decreased backwardly from the anterior area. There were significant differences in latency of SSR between the tip of the tongue and the molar areas of the oral cavity (p < 0.05). Reduction in the alpha frequency band was observed after thermal stimuli, and there were statistical differences between baseline and thermal stimuli in all four degrees of temperatures (p < 0.05).ConclusionThe result of the experiment revealed that the autonomic and central nervous system (CNS) played important roles in thermal perception of oral mucosa and could be helpful for better understanding of pathological mechanism of burning mouth syndrome (BMS).

Relationships of autonomic dysfunction with disease severity and neuropathic pain features in fibromyalgia: is it really a sympathetically maintained neuropathic pain?

BackgroundThe pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP.MethodsTwenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire.ResultsFM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although non-significant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities.ConclusionsANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.

Pain-autonomic interaction is a reliable measure of pain habituation in healthy subjects.

BackgroundHabituation is a response decrement resulting from repeated stimuli. Reduced habituation to noxious stimuli is considered to be a proxy for central sensitization in subjects with chronic pain. Despite numerous investigations of pain habituation in relation to central sensitization, there is no consensus on the most sensitive and reliable readout, as well as analysis approach. Therefore, this study compared the usability and reliability of different readouts and habituation analysis approaches to measure pain habituation in response to repetitive heat simulation.MethodsThree blocks of 20 contact heat stimuli were applied on the volar forearm of 20 healthy subjects on two separate visits. Habituation was assessed by three different readouts: pain ratings, contact heat evoked potentials (CHEPs) and heat‐induced sympathetic skin responses (SSRs). In addition, two different habituation analysis approaches were used: between the three stimulation blocks (between‐block) and within the first stimulation block (within‐block).ResultsSignificant between‐block habituation for SSRs (p < 0.001), but not for pain ratings (p = 1.000) and CHEPs (p = 0.078) was found. There was significant within‐block habituation for pain ratings (p = 0.012) and SSRs (p < 0.001), but not for CHEPs (p = 0.246). Only the between‐block habituation of heat‐induced SSR was reliable between the two visits (first to second block: intraclass correlation coefficient [ICC] = 0.58, p = 0.030; first to third block: ICC = 0.64, p = 0.015).ConclusionHeat‐induced SSR as a measure of pain‐autonomic interaction revealed the strongest pain habituation and showed the highest test–retest reliability.

Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study.

Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.

Serum sclerostin and sympathetic skin response: relationship with myeloma bone disease

BackgroundMyeloma bone disease (MBD) is a common complication that significantly contributes to morbidity and mortality in multiple myeloma (MM). Serum sclerostin level and sympathetic activity can affect MBD. The purpose of this study is evaluation of serum sclerostin level and sympathetic activity (using sympathetic skin response “SSR”) in MM patients, and studying the relationship between both of them as well as their relationship with MBD. 35 smoldering myeloma patients (group I) and 35 newly diagnosed MM (group II) and 35 controls (group III) were included in the study. All the participants were subjected to complete history taking, and clinical examination. Assessment of serum sclerostin level, SSR, MM stages [by the international staging system (ISS)], MBD grading (according to the Durie–Salmon staging system) were done for all patients within 7 days from the diagnosis.ResultsUndetectable and decreased SSR amplitude are significantly more detected in group I and II (compared with group III). Autonomic manifestations, and loss of SSR is significantly more detected in group II than group I. Autonomic manifestations were absent in group III. SSR amplitude of median and tibial nerves is significantly decreased in group II than group I and III. MBD was detected in all patients of group II. Serum sclerostin and LDH were significantly increased in group II than group I. Group I and II had significantly higher levels of sclerostin when compared with group III. Group II had significantly higher levels of sclerostin and lower levels of ALP in comparison with group I. Serum sclerostin level was correlated positively with LDH and negatively with ALP and SSR amplitude. MBD was significantly affected by ISS stage III, LDH level, SSR affection and serum sclerostin level ≥ 0.40 ng/ml. SSR response affection was the most significant risk factor for advanced MBD followed by increased sclerostin level.ConclusionsSerum sclerostin level was significantly increased and sympathetic activity was significantly decreased in MBD. Loss of the SSR response was the most significant risk factor for advanced MBD followed by increased sclerostin level.RecommendationsPotentially validating the use of bone-turnover markers in larger studies, in addition to electrophysiological examination of SSR to stratify patients who are at high-risk for progressive MBD, as the use of newer agents with anabolic effects such as anti-sclerostin antibodies have shown potential in repair of MBD. These newer agents could potentially change the treatment landscape in patients with MBD.

The effect of oral contraceptive use on sympatic nerve activity in patients with polycystic ovary syndrome

Objective High sympathetic nerve activity, is thought to be a cardiovascular risk factor, has been shown to correlate with circulating high testosterone levels. However its role on the pathophysiology of the polycystic ovarian syndrome has not been clearly established. The aim of our study is to compare the sympathetic nerve activity between polycystic ovarian syndrome and control group and to determine whether the use of oral contraceptives for contraception has any effect on this activity. Materials and methods Our study has designed as a prospective, case–control study including patients diagnosed with polycystic ovarian syndrome. Antropometric measurements were calculated, hormone levels were measured and sympathetic skin response and heart rate variability measurements were performed in the laboratory to assess sympathetic activity before starting oral contraceptive pill therapy and at the end of 1 month follow up. Results In the baseline condition LH/FSH ratio, LH, DHEAS, and total testosterone levels were significantly higher in women with PCOS. After 1 month of treatment, reductions in Ferriman–Gallwey score, ovarian volumes, number of follicles, LH/FSH ratio, LH, and androgen hormone levels were statistically significant. The mean values of sympathetic skin response amplitude and R–R analysis-Valsalva test were higher in PCOS group as compared to the control group. However, these differences were not statistically significant. Similarly, no statistically significant difference in SSR latency and R–R analysis-standup test were demonstrated between PCOS and control groups. Conclusion In conclusion, our study supports the increased sympatovagal activity in patients with polycystic ovarian syndrome.

A Systematic Review and Meta-Analysis of the Prevalence of Small Fibre Impairment in Patients with Fibromyalgia.

Converging evidence shows that patients with fibromyalgia syndrome have signs of small fibre impairment, possibly leading to pain and autonomic symptoms, with a frequency that has not yet been systematically evaluated. To fill this gap, our review aims to define the frequency of somatic and autonomic small fibre damage in patients with fibromyalgia syndrome, as assessed by objective small fibre-related testing. We found 360 articles on somatic and autonomic small fibre assessment in patients with fibromyalgia. Out of the 88 articles assessed for eligibility, 20 were included in the meta-analysis, involving 903 patients with fibromyalgia. The estimated prevalence of somatic small fibre impairment, as assessed with skin biopsy, corneal confocal microscopy, and microneurography, was 49% (95% confidence interval (CI): 39–60%, I2 = 89%), whereas the estimated prevalence of autonomic small fibre impairment, as assessed with heart rate variability, sympathetic skin response, skin conductance, and tilt testing, was 45% (95% CI: 25–65%, I2 = 91%). Our study shows that a considerable proportion of patients with fibromyalgia have somatic and autonomic small fibre impairment, as assessed by extensive small fibre-related testing. Nevertheless, the heterogeneity and inconsistencies across studies challenge the exact role of small fibre impairment in fibromyalgia symptoms.

Autonomic Function Tests, Heart Rate Variability, and Electrophysiological Evaluation in Patients With a Primary Episodic Headache: An Observational Study.

Cranial autonomic symptoms are typically associated with the trigeminal autonomic cephalalgias and also present in substantial cases of migraine. Autonomic nervous system dysfunctions are also been reported in headache disorders and postulated to promote headache attacks. This study was aimed to evaluate the parasympathetic and sympathetic autonomic functions tests in patients with a episodic primary headache and to investigate, if any, electrophysiological abnormalities in the blink reflex test and sympathetic skin response test in these patients. In this cross-sectional study, a total of 100 patients, 50 patients each of migraine and tension-type headache attending the neurology OPD and fulfilling the diagnostic criteria of headache disorders were enrolled. Autonomic functions tests were performed in the Department of Physiology, whereas electrophysiological tests were powered by the Editorial Manager and ProduXion Manager from Aries Systems Corporation performed in the Department of Neurology. Significant association ( P < 0.05) was observed in "blood pressure response to sustained handgrip" (sympathetic activity) and "heart rate response to Valsalva maneuver" (parasympathetic activity) among patients with migraine. Although the mean sympathetic skin response latency of patients with migraine was within the normal range, it was significantly prolonged in comparison with the control group. "Blood pressure response to sustained handgrip" and "heart rate variability" were found to be significantly ( P < 0.05) different in patients with a tension-type headache. The blink reflex test was observed to be normal in all patients with a headache. Patients with migraine showed a significant dysautonomia in category three of the Ewing battery for autonomic functional disability. Autonomic functional abnormality, both sympathetic and parasympathetic, does exist in patients with a primary episodic headache.

Pilomotor seizures in autoimmune limbic encephalitis: description of two GAD65 antibodies- related cases and literature review

BackgroundIctal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies. MethodsWe selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP. ResultsOf 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy. Discussion and conclusionThe prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.

Autonomic dysfunction in amyotrophic lateral sclerosis: A neurophysiological and neurosonology study.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs, and thus ALS is considered a multisystem disorder. The aim of this study is to investigate autonomous nervous system involvement in ALS. We investigated 21 ALS patients and 28 age-matched controls. ALS patients were assessed for disease severity with the Revised-ALS Functional Rating Scale (ALSFSR) and for the presence of autonomic symptoms with the Composite Autonomic Symptom Score scale. Sympathetic nervous system was evaluated by sympathetic skin response (SSR) and parasympathetic nervous system by ultrasonography of vagus nerve (VN) at the level of the thyroid gland. SSR latencies were shorter and SSR amplitudes were higher in controls compared to ALS patients. The cross-sectional area (CSA) of the VN was significantly smaller in ALS patients (mean CSA right/left: 1.73±0.62 mm2 /1.47±0.53 mm2 ) compared to controls (mean CSA right/left: 2.91±0.79 mm2 /2.30±0.80 mm2 ), right: p <. 001, left: p <. 001. There was a significant negative correlation between disease duration and CSA of left-VN (r = -0.493, p = .023). This correlation was attenuated between disease duration and CSA of right-VN (r = -0.419, p = .059). ALSFSR-R was positively correlated to CSA of right-VN (p = .006, r = 0.590). CSA of VN did not correlate with bulbar involvement. This study confirms the presence of autonomic dysfunction in ALS patients and provides evidence of VN atrophy that correlates with disease severity and duration and is independent of bulbar involvement. Degeneration of dorsal nucleus neurons of the VN is hypothesized.

Autonomic dysfunction detected by skin sympathetic response in Lambert-Eaton myasthenic syndrome: a case report

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a type of paraneoplastic syndrome that may initially manifest itself with proximal weakness and gait abnormalities. Approximately up to 50% of LEMS patients have a primary autonomic dysfunction.Case presentationWe present here a case of a 75-year-old male with symmetric proximal muscle weakness, dry mouth and constipation. The cutaneous response to scratch and upright tilt-table testing were positive. A repetitive nerve stimulation test showed that there was a decremental response of compound muscle action potential (CMAP) amplitude at 3 Hz while an incremental response at 20 Hz. The presence of antibodies against voltage-gated calcium channels (VGCC) confirmed the diagnosis. Because of the prominent symptom of autonomic disorder, the patient further underwent the test of skin sympathetic response (SSR). Lower amplitude and longer response duration were found in palms, while it evoked no response in soles.ConclusionsIn this case, we present the detailed results of SSR test on a patient suffering LEMS with autonomic disorder. Since autonomic dysfunction has a significant impact on clinical management and SSR test is an effective detection method, we recommend that SSR test be performed on patients with LEMS regularly.

Comparative effects of tensioning and sliding neural mobilization on peripheral and autonomic nervous system function: A randomized controlled trial.

Background:Although different types of neural mobilization (NM) exercises induce different amounts of longitudinal nerve excursion and strain, the question whether the increased longitudinal stress and nerve excursion from sliding or tensioning intervention may subtly affect the neural functions has not been answered yet.Objective:To compare the effects of tensioning NM versus sliding NM of the median nerve on peripheral and autonomic nervous system function.Methods:In this randomized controlled trial, 90 participants were randomly assigned to tensioning NM, sliding NM, or sham NM. The neurophysiological outcome measures included peak-to-peak amplitude of the dermatomal somatosensory evoked potential (DSSEP) for dermatomes C6, C7, C8, and T1. Secondary outcome measures included amplitude and latency of skin sympathetic response. All outcome measures were assessed pretreatment, immediately after the two weeks of treatment and one week after the last session of the treatment.Results:A 2-way repeated measures ANOVA revealed significant differences between the three groups. The post hoc analysis indicated that tensioning NM significantly decreased the dermatomal amplitude for C6, C7, C8, and T1 (). Sympathetic skin responses in the gliding NM group showed lower amplitudes and prolonged latencies post-treatment when compared to tensioning NM group (). In contrast, no significant changes were observed in the DSSEPs and skin sympathetic responses for participants in the sham treatment group ().Conclusions:A tensioning NM on the median nerve had a possible adverse effect on the neurophysiology variables of the nerves involved in the neural mobilization. Thus, tensioning NM with the current parameters that place increased stress and strain on the peripheral nervous system should be avoided.

Sympathetic skin responses and electromyographic reaction times in chronic autoimmune thyroiditis: An overlooked electrodiagnostic study.

Objectives This study aims to evaluate peripheral nerve functions, sympathetic skin responses (SSRs), and electromyographic (EMG) reaction times in hypothyroid patients and to compare them to healthy individuals. Patients and methods Between January 2007 and September 2007, a total of 54 patients with Hashimoto’s thyroiditis including 35 euthyroid (3 males, 32 females; mean age: 45.2±10.2 years; range, 35 to 60 years) and 19 with subclinical hypothyroidism (2 males, 17 females; mean age: 43.2±12.6 years; range, 40 to 65 years) were included in the study. The control group consisted of 35 healthy individuals (5 males, 30 females; mean age: 39.1±9.3 years; range, 29 to 52 years). Nerve conduction studies (NCSs), SSRs of the hand and foot obtained by stimulation of the contralateral median nerve, and EMG reaction times of the extensor indicis proprius muscle were performed in all subjects. Results There was no significant difference in peripheral NCSs and SSRs between patients and the control group. However, reaction times were longer in the AIT patients compared to the healthy individuals suggesting alterations in cognitive function related to the primary disease process in AIT. Conclusion Electrodiagnosis of autonomic nervous system involvement and cognitive impairment can be challenging in AIT. However, EMG reaction times and SSRs are practical and useful tools that are often overlooked. On the other hand, SSRs may be combined with more quantitative tests, such as sudomotor axon reflex testing, to allow us to better determine the extent of involvement of the autonomic nervous system in AIT.