Dementia classification using a graph neural network on imaging of effective brain connectivity.

Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common forms of neurodegenerative diseases. The literature suggests that effective brain connectivity (EBC) has the potential to track differences between AD, PD and healthy controls (HC). However, how to effectively use EBC estimations for the research of disease diagnosis remains an open problem. To deal with complex brain networks, graph neural network (GNN) has been increasingly popular in very recent years and the effectiveness of combining EBC and GNN techniques has been unexplored in the field of dementia diagnosis. In this study, a novel directed structure learning GNN (DSL-GNN) was developed and performed on the imaging of EBC estimations and power spectrum density (PSD) features. In comparison to the previous studies on GNN, our proposed approach enhanced the functionality for processing directional information, which builds the basis for more efficiently performing GNN on EBC. Another contribution of this study is the creation of a new framework for applying univariate and multivariate features simultaneously in a classification task. The proposed framework and DSL-GNN are validated in four discrimination tasks and our approach exhibited the best performance, against the existing methods, with the highest accuracy of 94.0% (AD vs. HC), 94.2% (PD vs. HC), 97.4% (AD vs. PD) and 93.0% (AD vs. PD vs. HC). In a word, this research provides a robust analytical framework to deal with complex brain networks containing causal directional information and implies promising potential in the diagnosis of two of the most common neurodegenerative conditions.

Spatial-temporal graph convolutional network for Alzheimer classification based on brain functional connectivity imaging of electroencephalogram.

Functional connectivity of the human brain, representing statistical dependence of information flow between cortical regions, significantly contributes to the study of the intrinsic brain network and its functional mechanism. To fully explore its potential in the early diagnosis of Alzheimer's disease (AD) using electroencephalogram (EEG) recordings, this article introduces a novel dynamical spatial-temporal graph convolutional neural network (ST-GCN) for better classification performance. Different from existing studies that are based on either topological brain function characteristics or temporal features of EEG, the proposed ST-GCN considers both the adjacency matrix of functional connectivity from multiple EEG channels and corresponding dynamics of signal EEG channel simultaneously. Different from the traditional graph convolutional neural networks, the proposed ST-GCN makes full use of the constrained spatial topology of functional connectivity and the discriminative dynamic temporal information represented by the 1D convolution. We conducted extensive experiments on the clinical EEG data set of AD patients and Healthy Controls. The results demonstrate that the proposed method achieves better classification performance (92.3%) than the state-of-the-art methods. This approach can not only help diagnose AD but also better understand the effect of normal ageing on brain network characteristics before we can accurately diagnose the condition based on resting-state EEG.

EEG Recordings as Biomarkers of Pain Perception: Where Do We Stand and Where to Go?

INTRODUCTION: The universality and complexity of pain, which is highly prevalent, yield its significance to both patients and researchers. Developing a non-invasive tool that can objectively measure pain is of the utmost importance for clinical and research purposes. Traditionally electroencephalography (EEG) has been mostly used in epilepsy; however, over the recent years EEG has become an important non-invasive clinical tool that has helped increase our understanding of brain network complexities and for the identification of areas of dysfunction. This review aimed to investigate the role of EEG recordings as potential biomarkers of pain perception. METHODS: A systematic search of the PubMed database led to the identification of 938 papers, of which 919 were excluded as a result of not meeting the eligibility criteria, and one article was identified through screening of the reference lists of the 19 eligible studies. Ultimately, 20 papers were included in this systematic review. RESULTS: Changes of the cortical activation have potential, though the described changes are not always consistent. The most consistent finding is the increase in the delta and gamma power activity. Only a limited number of studies have looked into brain networks encoding pain perception. CONCLUSION: Although no robust EEG biomarkers of pain perception have been identified yet, EEG has potential and future research should be attempted. Designing strong research protocols, controlling for potential risk of biases, as well as investigating brain networks rather than isolated cortical changes will be crucial in this attempt.

Brain functional and effective connectivity based on electroencephalography recordings: A review.

Functional connectivity and effective connectivity of the human brain, representing statistical dependence and directed information flow between cortical regions, significantly contribute to the study of the intrinsic brain network and its functional mechanism. Many recent studies on electroencephalography (EEG) have been focusing on modeling and estimating brain connectivity due to increasing evidence that it can help better understand various brain neurological conditions. However, there is a lack of a comprehensive updated review on studies of EEG-based brain connectivity, particularly on visualization options and associated machine learning applications, aiming to translate those techniques into useful clinical tools. This article reviews EEG-based functional and effective connectivity studies undertaken over the last few years, in terms of estimation, visualization, and applications associated with machine learning classifiers. Methods are explored and discussed from various dimensions, such as either linear or nonlinear, parametric or nonparametric, time-based, and frequency-based or time-frequency-based. Then it is followed by a novel review of brain connectivity visualization methods, grouped by Heat Map, data statistics, and Head Map, aiming to explore the variation of connectivity across different brain regions. Finally, the current challenges of related research and a roadmap for future related research are presented.

A Revised Hilbert-Huang Transformation to Track Non-Stationary Association of Electroencephalography Signals.

The time-varying cross-spectrum method has been used to effectively study transient and dynamic brain functional connectivity between non-stationary electroencephalography (EEG) signals. Wavelet-based cross-spectrum is one of the most widely implemented methods, but it is limited by the spectral leakage caused by the finite length of the basic function that impacts the time and frequency resolutions. This paper proposes a new time-frequency brain functional connectivity analysis framework to track the non-stationary association of two EEG signals based on a Revised Hilbert-Huang Transform (RHHT). The framework can estimate the cross-spectrum of decomposed components of EEG, followed by a surrogate significance test. The results of two simulation examples demonstrate that, within a certain statistical confidence level, the proposed framework outperforms the wavelet-based method in terms of accuracy and time-frequency resolution. A case study on classifying epileptic patients and healthy controls using interictal seizure-free EEG data is also presented. The result suggests that the proposed method has the potential to better differentiate these two groups benefiting from the enhanced measure of dynamic time-frequency association.

The Role of Oxidative Stress in Peripheral Neuropathy.

Peripheral neuropathy (PN) is a common disease affecting about 5% of the general population after the age of 50. Causes of PN are numerous and include genetic, diabetes, alcohol, vitamin deficiencies, and gluten sensitivity among others. This systematic review aimed to study the association between oxidative stress and PN in an attempt to better understand PN pathogenesis. A computer-based, systematic search was conducted on the PubMed database, and ensuing data from included articles was analyzed and discussed in this review. Sixty-nine papers were eligible and were used for this review. Peripheral neuropathy is associated with an increase of reactive oxygen species and a decrease in endogenous antioxidants. Genetic predisposition to oxidative damage may be a factor. Antioxidant treatment is promising regarding treatment. Though further research is necessary to better understand the underlying mechanism, it is evident that oxidative stress is implicated in the pathogenesis of - or is at least systematically present in - PN.

Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A Systematic Review.

INTRODUCTION: Repetitive magnetic stimulation (rMS) is a safe and well-tolerated intervention. Transcranial magnetic stimulation (TMS) is used for the treatment of depression and for the treatment and prevention of migraine. Over the last few years, several reports and randomised controlled studies of the use of rMS for the treatment of pain have been published. The aim of this systematic review was to identify the available literature regarding the use of rMS in the treatment of peripheral neuropathic pain. METHODS: After a systematic Medline search we identified 12 papers eligible to be included in this review. RESULTS: The majority of the studies were on patients with phantom limb pain, followed by radiculopathy, plexopathy, post-traumatic pain and peripheral neuropathy. The treatment protocols vary significantly from study to study and, therefore, pooling the results together is currently difficult. However, rMS has a definite immediate effect in pain relief which, in the majority of studies, is maintained for a few weeks. CONCLUSION: rMS seems to be a promising intervention in the treatment of peripheral neuropathic pain. Further research is in the field is needed. Use of neuronavigation might increase the precision of stimulation and subsequently its effectiveness.

Pain as a determinant of health-related quality of life in patients with carpal tunnel syndrome; a case-controlled study.

Introduction: Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes. It causes both positive and negative symptoms in the hands. These symptoms, especially pain, can be debilitating, which can in turn have a negative effect on patients' quality of life (QoL). The aim of this cross-sectional case-controlled study was two-fold; to compare the QoL of patients with CTS and subjects without CTS and to determine the effect of pain on QoL in patients with CTS.Methods: All patients underwent nerve conduction studies (NCS) and were classified into mild, moderate, severe. QoL was assessed via the SF-36 questionnaire.Results: Fifty-one patients and 45 age- and gender-matched controls were recruited. Prevalence of pain (determined as scoring 4 or above on a visual analog scale) in CTS was 39.2%. CTS patient health-related QOL scores were significantly reduced (p < 0.001) across all of the SF-36 domains, compared to the healthy control group scores. After adjusting for gender presence of pain was still significantly negatively correlated with scores for physical functioning (beta -0.283, p = 0.036).Conclusions: Patients with CTS have a significantly worse QoL compared to subjects without CTS. In addition, the presence of pain is a significant determinant of physical functioning in patients who have been diagnosed with CTS.

Tibial motor and sural electrophysiological relationship in subjects without and patients with mild axonal peripheral neuropathy.

The distal motor fibers of the tibial and sural nerves are predominantly derived from the S1 root. We aimed to describe the electrophysiological relationship of these two nerves. Clinical, radiological and neurophysiological data of patients with mild, length-dependent, peripheral neuropathy (PN) and subjects without PN were retrospectively collected and analyzed. Eighty-eight individuals without PN and 24 patients with mild axonal PN who had no evidence of lumbosacral radiculopathy were included for analysis. Significant positive correlations were observed for the tibial CMAP and the sural SNAP for both controls and patients. Multivariate linear regression analyses showed that the predicted tibial CMAP can be calculated using the following equations: for male subjects without PN, tibial CMAP = 20.7 - 0.21 × age; for female subjects without PN, tibial CMAP = 23.3 - 0.21 × age and for patients with mild PN, tibial CMAP = 2.7 + sural SNAP. This study demonstrates the high correlation between the tibial CMAP and the sural SNAP in subjects without PN and patients with mild axonal peripheral neuropathy, and provides mathematical equations for the calculation of the predicted tibial CMAP for such individuals.

Small fiber neuropathy in coeliac disease and gluten sensitivity.

Objectives: The commonest types of peripheral neuropathy in the context of Coeliac Disease (CD) and gluten sensitivity (GS) are length-dependent symmetrical sensorimotor neuropathies and sensory ganglionopathies. In patients with such neuropathy, (gluten neuropathy), peripheral neuropathic pain is prevalent suggesting involvement of small fibers. The purpose of this report was to describe the clinical characteristics of patients with CD or GS and pure small fiber neuropathy (SFN). Methods: We reviewed the records of all patients that had been referred to the Gluten-Related Neurological Disorders clinic who had clinical and neurophysiological evidence of SFN. All patients had serological evidence of gluten sensitivity (GS) prior to commencing GFD. All patients were offered a duodenum biopsy. Patients with comorbidities that could cause SFN were excluded. Results: We identified 13 patients (9 males) with SFN and gluten sensitivity. Of 11 patients who underwent duodenal biopsy 10 had evidence of enteropathy (CD). Mean age at onset of pain was 53.5 ± 11.4 years (range 34-72) and mean age of CD/GS diagnosis was 50.8 ± 10.4 years (range 34-68). In 8 patients (61.5%) pain was the presenting feature. Neurophysiological assessment suggested a length-dependent small fiber neuropathy in 11 patients, whereas in 2, a non-length dependent pattern was identifying suggesting that the predominant pathology lies in the dorsal root ganglia. Conclusion: SFN can be a presenting feature of CD and GS and, therefore, screening for CD and GS should be included in the diagnostic workup of patients with idiopathic SFN.

Anxiety and depression in patients with suspected carpal tunnel syndrome - A case controlled study.

PURPOSE: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy causing significant, and often disabling, pain. We aimed to establish the prevalence of anxiety and depressive symptoms in patients who were referred with suspected CTS and identify potential determinants. METHODS: All patients underwent nerve conduction studies (NCS) and were classified into mild, moderate, severe, and no CTS groups. Volunteers, without symptoms or signs of CTS, formed the control group. Anxiety and depressive symptoms were assessed via the Hospital Anxiety and Depression Scale. RESULTS: Ninety-one patients and 41 controls were recruited. Following NCS the patients were classified as follows: mild CTS (n = 20), moderate CTS (n = 21), severe CTS (n = 11), and no CTS (n = 31). CTS patients had significantly higher depression scores compared to controls but not anxiety scores. Patients experiencing pain and itchiness had significantly higher anxiety scores compared to those who did not. Patients who reported symptoms suggestive of CTS but did not meet the electrodiagnostic criteria for a diagnosis had significantly higher anxiety and depression scores compared to CTS patients and controls. CONCLUSIONS: Patients suffering with CTS may be at an increased risk of depression. Experiencing pain in CTS may further increase the likelihood of experiencing mental health difficulties. Poor mental health can give rise to functional symptoms, similar to those seen in CTS, demonstrating the need for electrophysiological testing before considering surgical intervention.

Tremor after long term lithium treatment; is it cortical myoclonus?

INTRODUCTION: Tremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult. METHODS: We identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum. RESULTS: Seven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42-77) after lengthy exposure to lithium (range 7-40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse. CONCLUSIONS: A synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.

Electrophysiological determinants of the clinical severity of axonal peripheral neuropathy.

INTRODUCTION: Electrophysiological diagnosis of axonal peripheral neuropathy (PN) is based on the attenuated amplitudes of nerve conduction studies (NCS), or a reduced sural/radial amplitude ratio (SRAR). We aimed to identify the electrophysiological determinants of the clinical severity of PN. METHODS: Patients with chronic axonal PN underwent detailed NCS. The clinical severity of PN was determined based upon the overall neuropathy limitations scale (ONLS). RESULTS: Ninety-five patients (71.6% males, mean age 71.9 ± 9.0 years) were recruited. Significant correlations were observed between the radial sensory nerve action potential (SNAP) and the ONLS total score (Spearman's rho -0.382, p < 0.001); and between the tibial compound muscle action potential and the ONLS leg score (Spearman's rho -0.283, p = 0.005). No correlations between the SRAR and the ONLS scores were found. DISCUSSION: The radial SNAP is the strongest electrophysiological determinant of PN severity and might be useful for monitoring disease progression or response to treatment. Muscle Nerve 59:491-493, 2019.

Increased Oxidative Stress as a Risk Factor in Chronic Idiopathic Axonal Polyneuropathy.

Chronic idiopathic axonal polyneuropathy (CIAP) is a disorder with insidious onset and slow progression, where no etiology is identified despite appropriate investigations. We aimed to investigate the role of oxidative stress as a risk factor for the pathogenesis of CIAP. Sera of patients with CIAP were tested for protein carbonyl (PC) and 8-hydroxydeoxyguanosine (8H). As a control group, we recruited patients with gluten neuropathy. Twenty-one patients with CIAP and 21 controls were recruited. The two groups did not differ significantly regarding demographics or clinical characteristics (i.e., neuropathy type or disease severity). After adjusting for gender, having CIAP was positively correlated with both the 8H titer (standardized beta coefficient 0.349, p = 0.013) and the PC titer (standardized beta coefficient 0.469, p = 0.001). Oxidative stress appears to be increased in CIAP and might have a role in the pathogenesis of the disease.

Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet.

BACKGROUND AND AIM: Peripheral neuropathy is a common extraintestinal manifestation of gluten sensitivity (gluten neuropathy). We aimed to establish the prevalence of neuropathic pain in patients with otherwise idiopathic PN and gluten sensitivity (positive antigliadin, endomysial, and/or transglutaminase antibodies, with or without enteropathy) and to describe any contributory factors. METHODS: All consecutive patients with gluten neuropathy (GN) attending a specialist gluten/neurology clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analog scale. Overall Neuropathy Limitations Scale was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants' general mental health status. RESULTS: In total, 60 patients (76.7% males, mean age 69.9 ± 10.1 years) with GN were recruited. Neuropathic pain was present in 33 patients (55.0%). Comparison between groups of painful and not painful GN did not show significant differences regarding age, gender, neuropathy severity and neuropathy type. Patients with painless GN were more likely to be on a strict gluten-free diet (55.6 versus 21.2%, p = 0.006). Patients with painful GN presented with significantly worse MHI-5 score (75.9 ± 13.8 versus 87.4 ± 8.1, p < 0.001). Multivariate analysis showed that, after adjusting for age, gender and MHI-5, strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7% (95% CI 47.2-97.6%, p = 0.006). CONCLUSION: Neuropathic pain is very prevalent in GN and is associated with poorer mental health status. Strict gluten-free diet might be protective as it is associated with a significant reduction of the odds of peripheral neuropathic pain associated to GN.

Quality of Life in Patients with Gluten Neuropathy: A Case-Controlled Study.

BACKGROUND: Gluten neuropathy (GN) is defined as an otherwise idiopathic peripheral neuropathy in the presence of serological evidence of gluten sensitivity (positive native gliadin antibodies and/or transglutaminase or endomysium antibodies). We aimed to compare the quality of life (QoL) of GN patients with that of control subjects and to investigate the effects of a gluten-free diet (GFD) on the QoL. METHODS: All consecutive patients with GN attending a specialist neuropathy clinic were invited to participate. The Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of the neuropathy. The 36-Item Short Form Survey (SF-36) questionnaire was used to measure participants’ QoL. A strict GFD was defined as effectively being able to eliminate all circulating gluten sensitivity-related antibodies. RESULTS: Fifty-three patients with GN and 53 age- and gender-matched controls were recruited. Compared to controls, GN patients showed significantly worse scores in the physical functioning, role limitations due to physical health, energy/fatigue, and general health subdomains of the SF-36. After adjusting for age, gender, and disease severity, being on a strict GFD correlated with better SF-36 scores in the pain domain of the SF-36 (beta 0.317, p = 0.019) and in the overall health change domain of the SF-36 (beta 0.306, p = 0.017). CONCLUSION: In GN patients, physical dysfunctioning is the major determinant of poor QoL compared to controls. Routine checking of the elimination of gluten sensitivity-related antibodies that results from a strict GFD should be encouraged, as such elimination ameliorates the overall pain and health scores, indicating a better QoL.

Anti-MAG associated cerebellar ataxia and response to rituximab.

BACKGROUND: Myelin-associated glycoprotein (MAG) is a glycoprotein specific to Schwann cells. Schwann cells produce myelin for nerve cells in the peripheral nervous system. MAG also plays a role in the central nervous system (CNS) by maintaining myelin integrity and inhibiting axonal regeneration from cerebellar neurons. There is a well-established link between distal demyelinating neuropathy and anti-MAG antibodies in patients with monoclonal gammopathy of unknown significance. We describe a series of five patients with anti-MAG antibodies with evidence of cerebellar rather than just sensory ataxia and our experience of treatment with rituximab. METHODS: Cerebellar ataxia was clinically suspected and confirmed using magnetic resonance spectroscopy (MRS) of the cerebellum. All patients underwent detailed nerve conduction studies. RESULTS: Four patients were males. The ages ranged from 64 to 82 years. All patients were anti-MAG positive and also had IgM monoclonal gammopathy. Four patients had neuropathy, whilst one had no evidence of neuropathy. All patients were treated with rituximab and showed improvement in the MRS parameters of the cerebellum. CONCLUSION: Anti-MAG antibodies might be involved in the pathogenesis of idiopathic sporadic ataxias, even in the absence of peripheral neuropathy. Rituximab seems to be a promising therapeutic intervention for those cases.

Transglutaminase 6 antibodies in gluten neuropathy.

BACKGROUND: TG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies). METHODS: This was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy. RESULTS: Twenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy. CONCLUSIONS: We found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.

Cerebellar ataxia with sensory ganglionopathy; does autoimmunity have a role to play?

BACKGROUND AND PURPOSE: Cerebellar ataxia with sensory ganglionopathy (SG) is a disabling combination of neurological dysfunction usually seen as part of some hereditary ataxias. However, patients may present with this combination without a genetic cause. METHODS: We reviewed records of all patients that have been referred to the Sheffield Ataxia Centre who had neurophysiological and imaging data suggestive of SG and cerebellar ataxia respectively. We excluded patients with Friedreich's ataxia, a common cause of this combination. All patients were screened for genetic causes and underwent extensive investigations. RESULTS: We identified 40 patients (45% males, mean age at symptom onset 53.7 ± 14.7 years) with combined cerebellar ataxia and SG. The majority of patients (40%) were initially diagnosed with cerebellar dysfunction and 30% were initially diagnosed with SG. For 30% the two diagnoses were made at the same time. The mean latency between the two diagnoses was 6.5 ± 8.9 years (range 0-44). The commonest initial manifestation was unsteadiness (77.5%) followed by patchy sensory loss (17.5%) and peripheral neuropathic pain (5%).Nineteen patients (47.5%) had gluten sensitivity, of whom 3 patients (7.5%) had biopsy proven coeliac disease. Other abnormal immunological tests were present in another 15 patients. Six patients had malignancy, which was diagnosed within 5 years of the neurological symptoms. Only 3 patients (7.5%) were classified as having a truly idiopathic combination of cerebellar ataxia with SG. CONCLUSION: Our case series highlights that amongst patients with the unusual combination of cerebellar ataxia and SG, immune pathogenesis plays a significant role.

Rapid neurophysiological screening for sensory ganglionopathy: A novel approach.

Background and Aim: Pure sensory neuropathies involving the dorsal root ganglia are commonly referred to as sensory ganglionopathies (SG). Causes of SG can be inherited (as seen in Friedreich's ataxia) or acquired (e.g. immune-mediated or paraneoplastic). Diagnostic criteria for confirming SG have been published and consist of a combination of clinical and neurophysiological parameters. The aim of our study was to develop a neurophysiological method for rapid screening for diagnosis of SG. Methods: For each subject we obtained the sensory nerve action potentials (SNAPs) of five nerves (median, ulnar, radial, sural and superficial peroneal) bilaterally. In the presence of an entrapment neuropathy we obtained the SNAP of the medial antebrachial cutaneous nerves bilaterally. We estimated the number of pairs of nerves showing a SNAP asymmetry of >50% (difference of SNAPs/ lower SNAP). Results: Sixty-eight subjects, 34 patients with SG and 34 age and sex-matched controls, participated in the study. Among all subjects using a receiver operating characteristic (ROC) curve analysis, the area under the curve was 0.984 (95% CI, 0.960-1.000; SE, 0.012; p < .001). In order to detect SG, presence of SNAP asymmetry of >50% in 2 pairs of nerves, not explained by an entrapment neuropathy, shows a sensitivity of 97.1%, a specificity of 94.1%, a positive predictive value of 94.3% and a negative predictive value of 97.0. Conclusion: The number of pairs of nerves showing a SNAP asymmetry of >50% may be used as a novel rapid screening tool of patients with SG.