Time-varying model identification for time-frequency feature extraction from EEG data

A novel modelling scheme that can be used to estimate and track time-varying properties of nonstationary signals is investigated. This scheme is based on a class of time-varying AutoRegressive with an eXogenous input (ARX) models where the associated time-varying parameters are represented by multi-wavelet basis functions. The orthogonal least square (OLS) algorithm is then applied to refine the model parameter estimates of the time-varying ARX model. The main features of the multi-wavelet approach is that it enables smooth trends to be tracked but also to capture sharp changes in the time-varying process parameters. Simulation studies and applications to real EEG data show that the proposed algorithm can provide important transient information on the inherent dynamics of nonstationary processes

Safety, tolerability, and nocebo phenomena during transcranial magnetic stimulation: a systematic review and meta‐analysis of placebo‐controlled clinical trials

Background The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta‐analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. Methods After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. Results Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%‐3.2%) and 2.7% (95% CI 2.0%‐3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%‐22.6%) and 13.6% (95% CI 11.6%‐15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75‐3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta‐analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14‐7.40) and 2.93 times higher (95% CI 1.41‐6.07), respectively, in the active treatment groups compared to placebo. Conclusions TMS is a safe and well‐tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice

Chronic idiopathic axonal polyneuropathy: Prevalence of pain and impact on quality of life

BACKGROUND AND AIM: Chronic idiopathic axonal polyneuropathy (CIAP) is a term describing axonal neuropathies of insidious onset, with slow or no progression of the disease over at least 6 months and with no etiology being identified despite appropriate investigations. We aimed to establish the prevalence of pain in patients with CIAP and investigate the impact of pain on quality of life (QoL). METHODS: All consecutive patients with CIAP attending a specialist neuropathy clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analogue scale (VAS). Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF-36 questionnaire was used to measure participants' quality of life. RESULTS: Fifty-five patients with CIAP were recruited (63.6% male, mean age 73.4 ± 8.7 years). Based on the DN4 questionnaire, peripheral neuropathic pain was present in 33 patients (60.0%). After having adjusted for age, gender and disease severity pain showed significant negative correlations with the energy/fatigue domain of QoL (β = -0.259, p = 0.049), with the emotional well-being domain (β = -0.368, p = 0.007) and the general health perception domain (β = -0.356, p = 0.007). CONCLUSION: Pain is very prevalent in CIAP and is associated with poorer emotional well-being, worse general health perception, and increased fatigue

Stiff person syndrome and gluten sensitivity

Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention

Diagnostic criteria for primary autoimmune cerebellar ataxia—guidelines from an international task force on immune-mediated cerebellar ataxias

Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications

Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity

OBJECTIVES: Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefi t from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS. METHODS: We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years. RESULTS: Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confi rm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identifi ed no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%). CONCLUSIONS: The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms

Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to TG6

Background & Aims Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to TG6 increases the risk of neurologic defects in patients with a new diagnosis of celiac disease. Methods We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging (MRI) of the brain, MR spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction. Results Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from the MRI, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients–these patients had significant atrophy of subcortical brain regions compared to patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later. Conclusions In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurological deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurological manifestations amongst clinicians and reinforcement of adherence to a strict GFD by patients in order to avoid permanent neurological disability

A dementia classification framework using frequency and time-frequency features based on EEG signals.

Alzheimer's Disease (AD) accounts for 60-70% of all dementia cases, and clinical diagnosis at its early stage is extremely difficult. As several new drugs aiming to modify disease progression or alleviate symptoms are being developed, to assess their efficacy, novel robust biomarkers of brain function are urgently required. This study aims to explore a routine to gain such biomarkers using the quantitative analysis of Electroencephalography (QEEG). This paper proposes a supervised classification framework which uses EEG signals to classify healthy controls (HC) and AD participants. The framework consists of data augmentation, feature extraction, K-Nearest Neighbour (KNN) classification, quantitative evaluation and topographic visualisation. Considering the human brain either as a stationary or a dynamical system, both frequency-based and time-frequency-based features were tested in 40 participants. Results: a) The proposed method can achieve up to 99% classification accuracy on short (4s) eyes open EEG epochs, with the KNN algorithm that has best performance when compared to alternative machine learning approaches; b) The features extracted using the wavelet transform produced better classification performance in comparison to the features based on FFT; c) In the spatial domain, the temporal and parietal areas offer the best distinction between healthy controls and AD. The proposed framework can effectively classify HC and AD participants with high accuracy, meanwhile offering identification and localisation of significant QEEG features. These important findings and the proposed classification framework could be used for the development of a biomarker for the diagnosis and monitoring of disease progression in AD

Clinical characteristics and management of 50 patients with anti-GAD ataxia: gluten-free diet has a major impact

The objective of this study is to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. We performed a retrospective review of all patients with anti-GAD ataxia managed at the Sheffield Ataxia Centre over the last 25 years. We identified 50 patients (62% females) with anti-GAD ataxia. The prevalence was 2.5% amongst 2000 patients with progressive ataxia of various causes. Mean age at onset was 55 and mean duration 8 years. Gaze-evoked nystagmus was present in 26%, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in 100%. Nine patients (18%) had severe, 12 (24%) moderate and 29 (58%) mild ataxia. Ninety percent of patients had a history of additional autoimmune diseases. Family history of autoimmune diseases was seen in 52%. Baseline MR spectroscopy of the vermis was abnormal at presentation in 72%. Thirty-five patients (70%) had serological evidence of gluten sensitivity. All 35 went on gluten-free diet (GFD). Eighteen (51%) improved, 13 (37%) stabilised, 3 have started the GFD too recently to draw conclusions and one deteriorated. Mycophenolate was used in 16 patients, 7 (44%) improved, 2 stabilised, 6 have started the medication too recently to draw conclusions and one did not tolerate the drug. There is considerable overlap between anti-GAD ataxia and gluten ataxia. For those patients with both, strict GFD alone can be an effective treatment. Patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression