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

A single-sensor approach to quantify gait in patients with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is characterised by progressive lower-limb spasticity and weakness resulting in ambulation difficulties. During clinical practice, walking is observed and/or assessed by timed 10-metre walk tests; time, feasibility, and methodological reliability are barriers to detailed characterisation of patients’ walking abilities when instrumenting this test. Wearable sensors have the potential to overcome such drawbacks once a validated approach is available for patients with HSP. Therefore, while limiting patients’ and assessors’ burdens, this study aims to validate the adoption of a single lower-back wearable inertial sensor approach for step detection in HSP patients; this is the first essential algorithmic step in quantifying most gait temporal metrics. After filtering the 3D acceleration signal based on its smoothness and enhancing the step-related peaks, initial contacts (ICs) were identified as positive zero-crossings of the processed signal. The proposed approach was validated on thirteen individuals with HSP while they performed three 10-metre tests and wore pressure insoles used as a gold standard. Overall, the single-sensor approach detected 794 ICs (87% correctly identified) with high accuracy (median absolute errors (mae): 0.05 s) and excellent reliability (ICC = 1.00). Although about 12% of the ICs were missed and the use of walking aids introduced extra ICs, a minor impact was observed on the step time quantifications (mae 0.03 s (5.1%), ICC = 0.89); the use of walking aids caused no significant differences in the average step time quantifications. Therefore, the proposed single-sensor approach provides a reliable methodology for step identification in HSP, augmenting the gait information that can be accurately and objectively extracted from patients with HSP during their clinical assessment

Rapid identification of human muscle disease with fibre optic Raman spectroscopy

The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71–77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74–89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders

Rapid identification of human muscle disease with fibre optic Raman spectroscopy

The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 29 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71-80%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 78 – 89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders

Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy

There are growing numbers of adults with Duchenne Muscular Dystrophy living well into their fourth decade. These patients have complex medical needs that to date have not been addressed in the International standards of care. We sought to create a consensus based standard of care through a series of multi-disciplinary workshops with specialists from a wide range of clinical areas: Neurology, Cardiology, Respiratory Medicine, Gastroenterology, Endocrinology, Palliative Care Medicine, Rehabilitation, Renal, Anaesthetics and Clinical Psychology. Detailed reports of evidence reviewed and the consensus building process were produced following each workshop and condensed into this final document which was approved by all members of the Adult North Star Network including service users. The aim of this document is to provide a framework to improve clinical services and multi-disciplinary care for adults living with Duchenne Muscular Dystrophy

Adult North Star Network (ANSN): Consensus Document for Therapists Working with Adults with Duchenne Muscular Dystrophy (DMD) - Therapy Guidelines

BACKGROUND The survival of people with Duchenne Muscular Dystrophy (DMD) significantly increased due to improvements in standards of care (SOC) [1]. Consequently, DMD has evolved from a paediatric disease to a severe, chronic, multisystem, adult condition. The published international standards of care advocate specialist multidisciplinary health monitoring through proactive, anticipatory approaches to slow down the effects of the disease and allow advanced, informed decision-making [1–3]. Therapy starts as soon as the diagnosis is made and plays a vital role in symptom management in individuals to improve function, participation and effective quality of life. Therapy interventions for management, differ depending on the setting in which the care is being provided, specifically in terms of the expertise within the teams and resources available within these settings. People with DMD find that when they transition to adult services there is a dearth of expertise and limited access to therapy services. The survey conducted in the UK highlighted substantial differences between the care received by adults and children with the condition [2]. A large proportion of adults with DMD reported increased difficulties with access to professional physiotherapy, particularly at transition from childhood to adulthood. Additionally, having their functional abilities assessed regularly or receiving professional physiotherapy in general were both significantly more difficult to achieve within adult services in the UK. Furthermore, some of the major problems expressed by adults with DMD were mobility and transportation as well as, getting involved in leisure activities and work [3]. Therefore, while pediatric services are predominantly family-centred, after transition the paradigm of patient care changes towards individual-centred with focus on different therapy goals. Those become more tailored to the individuals’ needs, balancing quality of life and management options.This document is aimed at providing guidelines for physiotherapy, occupational therapy and speech and language considerations. The ‘Adult North Star Network’ (ANSN) was founded in 2015 to advance care of adults with DMD living in the UK and to develop a prospective natural history database. There are currently 28 adult centres within the network, caring for at least 700 DMD patients. Transition age is varied depending on services and is generally between the ages of 16 to 18. There is a wide range of severity affecting people with DMD transitioned to adult services, those who are steroid naive will have been permanent wheelchair users for many years and have profound muscle weakness. On the other hand, steroid treated patients will most commonly have good upper limb function, and some maybe ambulant at the time of transition. Additionally the specific type of genetic mutation, compliance to therapy and environmental factors may play a role in disease progression and presentation at transition. The aim of these guidelines is to support therapists working with adults with DMD with little or no experience to assist their clinical practice. Whilst the recommendations can be adopted by other health care systems in the world, we appreciate it will depend on resource availability

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Value of systematic genetic screening of patients with amyotrophic lateral sclerosis

Objective The clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care. Methods We performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases. Results 21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074). Conclusions Routine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients

Characteristics of 698 patients with dissociative seizures: A UK multicenter study

Objective We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. Methods We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. Results In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed. Significance Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment