Abstract Background Measurement of arterial CO2 (PaCO2) is the gold standard for diagnosis of sleep hypoventilation during polysomnography. However, arterial PaCO2 measurement is a labour-intensive and painful. Previous audit in our unit demonstrated ABGs are often delayed or omitted when requested. Continuous monitoring of transcutaneous carbon dioxide (TcCO2) is often used as a surrogate marker of PaCO2, however caution should be applied in interpreting TcCO2 due to the “sensor drift” phenomenon. Arterialized capillary blood gas (CBG) measurement has been described in various settings and is used in many respiratory units. Concordance with ABG and TcCO2, however, is poorly described in the literature. A retrospective review was performed to assess concordance of arterialized capillary CO2 level (PcCO2) with TcCO2 measured during routine polysomnography. Methods This is a retrospective audit of patients with provisional diagnosis of sleep-related hypoventilation syndrome who attended Sunshine Coast University Hospital Sleep Disorders Centre for overnight sleep studies. Continuous TcCO2 was monitored and arterialized PcCO2 measured at the outset and completion of study. CO2 results will be compared to assess concordance. Where an ABG was performed simultaneously with a CBG the concordance will be reported. Progress to Date Full results to follow. It is anticipated that 30-40 patients will be included. Few ABGs were performed. Anticipated outcome Initial evaluation suggests PcCO2 may be a viable alternative to ABG based on concordance with limited ABG data. PcCO2 may be superior to TcCO2 due to the common phenomenon of TcCO2 “drift”. A prospective study, utilising ABG, CBG and TcCO2 is needed.

OBJECTIVE:In amyotrophic lateral sclerosis (ALS), motor neurons become hyperexcitable and spontaneously discharge electrical impulses causing fasciculations. These can be detected by two noninvasive methods: high-density surface electromyography (HDSEMG) and muscle ultrasonography (MUS). We combined these methods simultaneously to explore the electromechanical properties of fasciculations, seeking a novel biomarker of disease. METHODS:Twelve ALS patients and thirteen healthy participants each provided up to 24 minutes of recordings from the right biceps brachii (BB) and gastrocnemius medialis (GM). Two automated algorithms (Surface Potential Quantification Engine and a Gaussian mixture model) were applied to HDSEMG and MUS data to identify correlated electromechanical fasciculation events. RESULTS:We identified 4,197 correlated electromechanical fasciculation events. HDSEMG reliably detected electromechanical events up to 30 mm below the skin surface with an inverse correlation between amplitude and depth in ALS muscles. Compared to Healthy-GM muscles (mean = 79.8 ms), electromechanical latency was prolonged in ALS-GM (mean = 108.8 ms; p = 0.0458) and ALS-BB (mean = 112.0 ms; p = 0.0128) muscles. Electromechanical latency did not correlate with disease duration, symptom burden, sum muscle power score or fasciculation frequency. CONCLUSIONS:Prolonged fasciculation electromechanical latency indicates impairment of the excitation-contraction coupling mechanism, warranting further exploration as a potential novel biomarker of disease in ALS. SIGNIFICANCE:This study points to an electromechanical defect within the muscles of ALS patients.

Objective: We collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials.Methods: We conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment.Results: Dating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways.Conclusions: Neurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden. Significance: Future trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures.(c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes.

It was with great interest that I read Baker & Williams’ persuasive account outlining the correct use of the term ‘fasciculation’.1 The plural ‘fasciculations’, they argue, has erroneously slipped into the medical vernacular since Denny-Brown and Pennybacker coined the singular term in 1938.2 Fasciculation, they emphasise, represents a ‘state of being’ and therefore is a binary entity; fasciculation is either present or it is not. On reading this fascinating etymological tour, I felt compelled to present a counter-argument. I propose that the oft-used plural form represents much more than mere solecism. There are alternative ‘…-ation’ words where the plural form is not only acceptable, …

Objectives: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. Methods: Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. Results: By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/- 0.2 SEM), specificity of 91.6% (+/- 0.1 SEM) and classification accuracy of 87.9% (+/- 0.1 SEM). An amplitude exclusion threshold (100 mu V) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). Conclusion: We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). Significance: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health. (C) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

Objective: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS. Methods: We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients. Results: A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials. Conclusion: Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians. Significance: Surface EMG techniques can enrich effective biomarker development in ALS. (C) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

OBJECTIVES:Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline. METHODS:Six ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection. RESULTS:Assessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2-13.1 minutes), processing times (10.7-49.5 seconds) and fasciculation frequencies (27.4-71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6-79.4 IQR). CONCLUSION:We hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings. SIGNIFICANCE:Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

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1. On page 2 (p1084), section 2.4, 1st para, line 3, the text currently reads: ''A bandpass filter (20-500 Hz) was applied without notch filtering."It should read: ''A bandpass filter (20-500 Hz) was applied with 50 Hz notch filtering."2. On page 6 (p1088), section 4 (Discussion), paras 4 (line 8) and 5 (line 1): the published references to Fig. 4 are wrong and in both instances should make reference to Fig. 3.

In the original publication of the article, under the heading Discussion, 1st paragraph, the sentence that reads as, "Nonetheless, our observed improvements of over 50% for OS and over 30% for DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies" should read as "Nonetheless, our observed improvements of over 50% for OS and DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies." Under the heading Discussion, 3rd paragraph, the sentence that reads as "We cannot discount the possibility …such as education, income and access to care [1, 7]" should read as "We cannot discount the possibility…such as education, income and access to care, which ultimately have on survival outcomes [1, 7]."

Background: The Exercise for Health (EfH) trials were randomized, controlled trials designed to evaluate an 8-month pragmatic, exercise intervention, commencing 6 weeks post-surgery for women with newly diagnosed breast cancer residing in urban- or rural/regional areas. Outcomes for these exploratory analyses were overall survival (OS), breast cancer-specific survival (BCS) and disease-free survival (DFS). Methods: Consenting urban-residing women (EfH 1, n=194) and rural/regional-residing women (EfH 2, n=143) were randomized to exercise or usual care. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for OS, BCS and DFS (exercise group, n=207, 65% urban women; usual care group, n=130, 46% urban women), with and without adjustment for prognostic factors including trial (urban/rural), age, body mass index, disease stage and presence of comorbidities. Further exploratory subgroup analyses were also conducted to assess whether effect on OS, BCS and DFS differed according to prognostic variables. Results: After a median follow-up of 8.3 years (IQR: 8.0-8.7 years) there were 11 (5.3%) deaths in the exercise group compared with 15 (11.5%) deaths in the usual care group (Table 1). HRs for the exercise group were: OS: 0.45, 95% CI=0.20-0.96; p=0.04; BCS: 0.61, 95% CI=0.25-1.46, p=0.26; and DFS: 0.66, 95% CI=0.38-1.17; p=0.16 (adjusted analyses yielded similar results). With the exception of BCS for those with a body mass index >30, all HRs for subgroup analyses favored exercise, with effect on OS for women of younger age ( Citation Format: Hayes SC, Steele M, Spence R, Gordon L, Battistutta D, Bashford J, Pyke C, Saunders C, Eakin E. Can exercise influence survival following breast cancer? Evidence from randomised, controlled trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-01.

Background: The rate of multidrug-resistant organisms (MDRO) colonisation in dialysis populations has increased over time. This study aimed to assess the effect of contact precautions and isolation on quality of life and mood for haemodialysis (HD) patients colonised with MDRO. Methods: Patients undergoing facility HD completed the Kidney Disease Quality of Life (KDQOL–SFTM), Beck Depression Inventory (BDI) and Personal Wellbeing-Index Adult (PWI-A). Patients colonised with MDRO were case-matched by age and gender with patients not colonised. Results: A total of 16 MDRO-colonised patients were matched with 16 controls. Groups were well matched for demographics and co-morbidities, other than a trend for older dialysis vintage in the MDRO group [7.2 years (interquartile range 4.6–10.0) compared to 3.2 (1.4–7.6) years, p=0.05]. Comparing MDRO-positive with negative patients, physical (30.5±10.7 vs. 34.6±7.3; p=0.2) and mental (46.5±11.2 vs. 48.5±12.5; p = 0.6) composite scores were not different between groups. The MDRO group reported poorer sleep quality (p=0.01) and sleep patterns (p=0.05), and lower social function (p=0.02). BDI scores were similar (MDRO-positive 10(3.5–21.0) vs. MDRO-negative 12(6.5–16.0), p=0.6). PWI-A scores were also similar in both groups; however, MDRO patients reported lower scores for “feeling safe”, p=0.03. Conclusion: While overall scores of quality of life and depression were similar between groups, the MDRO group reported poorer outcomes in sleep and social function. A larger cohort and qualitative interviews may give more detail of the impact of contact precautions and isolation on HD patients. The necessity for contact precautions for different MDRO needs consideration.

Background: Amyloidosis and multiple myeloma result in extracellular deposition of insoluble fibrillary protein in the body. Untreated median survival had been previously documented at 12 months, or 5 months with cardiac involvement. Chemotherapy and peripheral blood stem cell transplantation (PBSCT) have been shown to dramatically improve survival, with haematologic remission. Regression of cardiac changes has previously been shown, as assessed by echocardiography (TTE). TTE and cardiac magnetic resonance imaging (cMRI) in cardiac amyloidosis survivors with regression are compared Results: Previously, 15 amyloid patients were identified with regression of cardiac features on TTE. Currently, five patients survive, with a patient lost to follow-up. One patient could not participate. Four patients were analysed. Mean age was 49 years. Average survival from PBSCT was 137 months. Mean time to regression on TTE was 22 months. Significant reduction in the septal and posterior wall thicknesses, left atrial area and diastolic dysfunction were shown, compared to pre-PBSCT measurements on TTE. TTE and MRI wall thickness and ejection fractions (EF) were not significantly different, after PBSCT. The classical apical sparing pattern on strain imaging was seen in 50% of TTE post PBSCT. All patients had diffuse, patchy gadolinium enhancement on MRI after PBSCT Conclusions: Treatment of cardiac amyloidosis with chemotherapy and PBSCT may result in regression of abnormalities on TTE and in prolonged survival. TTE and MRI measurements appear similar. Gadolinium imaging suggests that infiltration persists despite regression. Nonetheless, significant cardiac improvement with prolonged survival are seen.

Adverse changes in nutrition-related outcomes including quality of life (QoL) occur after PBSC transplantation. This randomised controlled trial aims to evaluate the impact of nutrition and exercise counselling provided at hospital discharge on nutritional status, body composition and QoL post transplantation. Usual care (UC) (n=19) received no intervention after discharge; extended care (EC) (n=18) received fortnightly telephone counselling from a dietitian and exercise physiologist up to 100 days post transplantation. Nutritional status (patient-generated subjective global assessment, and diet history), QoL (EORTC QLQ-C30 version 3) and body composition (air displacement plethysmography) were assessed at pre-admission, discharge and 100 days post transplantation. Intervention groups were compared using two-sample t-tests of changes in the outcomes; results were adjusted using analysis of covariance. EC exhibited clinically important but not statistically significant increases in protein intake (14.7 g; confidence interval (CI) 95% −6.5, 35.9, P=0.165), cognitive functioning (7.2; CI 95% −7.9, 22.2, P=0.337) and social functioning (16.5; CI 95% −7.3, 40.3, P=0.165) compared with UC. Relative to pre-admission, EC experienced less weight loss than UC (−3.3 kg; CI 95% −6.7, 0.2, P=0.062). Physical activity was not significantly different between the groups. Ongoing nutrition and exercise counselling may prevent further weight loss and improve dietary intake and certain QoL components in autologous PBSC transplantation patients following hospitalisation.

Progressive multifocal leucoencephalopathy (PML) is an opportunistic infection caused by JC virus (JCV) in immunodeficient individuals. The pathological hallmark is irreversible white matter demyelination. The diagnosis is supported by the clinical presentation (subacute motor deficits, ataxia and cortical visual symptoms), characteristic findings on magnetic resonance imaging (MRI) of the brain (bilateral, asymmetric, well-demarcated, T2 hyperintense white matter lesions with no oedema) and JCV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). We obtained retrospective data for all JCV PCR test results performed on CSF samples between March 2002 and November 2011 from HIV-seropositive patients at Chelsea & Westminster Hospital NHS Trust. In total, 564 CSF samples from HIV-positive patients were tested for JCV during 117 months, of which seven (1.24%) were positive. Contemporaneous MRI imaging of the brain was performed in 360 of 564 patients (63.8%) (Table 1). The gold standard for diagnosis of PML is brain biopsy. However, this is often unsafe, unethical or unnecessary. The combination of an appropriate clinical presentation and typical findings on brain MRI is often sufficient to make the diagnosis, for which highly active antiretroviral therapy (HAART) is the evidence-based treatment1. The utility of JCV PCR testing in the CSF of HIV-seropositive individuals is under question (sensitivity for MRI-proven PML = 24–89.5% 2, 3). Unsurprisingly, the use of HAART has been shown to reduce the sensitivity of this test (57.5% vs. 89.5% in patients not on HAART 3). JCV was infrequently detected in the CSF of HIV-positive individuals over a 9-year period. Although JCV was more frequently found in the CSF of patients with MRI findings suggestive of PML, the detection rate was still <5%, suggesting a very high false negative rate for this test. CSF JCV testing should not be performed routinely when MRI of the brain is normal or suggestive of a noninfectious pathology. Even when PML is suspected on MRI of the brain, JCV CSF is unlikely to be positive. We conclude that many of these tests are unnecessary, offering a potential to significantly reduce costs without compromising patient care.