Revised Amyotrophic Lateral Sclerosis Functional Rating Scale Research Articles

Structural MRI correlates of amyotrophic lateral sclerosis progression

PurposeAmyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain...

Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis.

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.

Six-Minute Walk Test as a Measure of Walking Capacity in Ambulatory Individuals With Amyotrophic Lateral Sclerosis

ObjectiveTo determine the validity of the 6-minute walk test (6MWT) as an outcome measure to evaluate walking capacity in ambulatory patients with amyotrophic lateral sclerosis (ALS). DesignObservational study. SettingMultidisciplinary ALS clinic at an academic medical center. ParticipantsPatients with ALS (N=186) who ambulate without (stage I) or with (stage II) an assistive device. InterventionsNot applicable. Main Outcome MeasureWalking distance obtained from the 6MWT. ResultsParticipants performed the 6MWT, 25-foot walk test (25FWT), Timed Up and Go (TUG) test, lower extremity maximum voluntary isometric contraction (MVIC), ALS Functional Rating Scale-Revised (ALSFRS-R), and forced vital capacity (FVC). Walking capacity was reduced to 66% predicted of healthy subjects (75.2%±22% in stage I; 42.6%±22% in stage II). The 6MWT correlated with all other outcome measures in ambulatory patients with ALS (25FWT: r=−.74, P≤.0001; TUG test: r=−.80, P≤.0001; MVIC: r=.64, P≤.0001; percent predicted FVC: r=.25, P≤.0007; ALSFRS-R: r=.52, P≤.0001; ALSFRS-R gross motor subscore: r=.71, P≤.0001). When ambulatory patients with ALS were stratified by stage of ambulation, the 6MWT was associated with all other outcome measures in stage I (25FWT: r=−.56, P≤.0001; TUG test: r=−.66, P≤.0001; MVIC: r=.51, P≤.0001; percent predicted FVC: r=.40, P≤.02; ALSFRS-R: r=.52, P≤.0001; ALSFRS-R gross motor subscore: r=.61, P≤.0001). In stage II, the 6MWT correlated with the 25FWT (r=−.83, P≤.0001), TUG test (r=−.77, P≤.0001), MVIC (r=.47, P≤.0001), and ALSFRS gross motor subscore (r=.61, P≤.0001), but not with percent predicted FVC (r=.09, P≤.513) or ALSFRS-R (r=.21, P≤.141). ConclusionsThe 6MWT is a valid measure of walking capacity of ambulatory patients with ALS that is associated with measures of lower extremity muscle strength and function in both stages of ambulation. The discordance between the 6MWT with the ALSFRS-R and percent predicted FVC in stage II ambulatory patients with ALS indicates that the 6MWT is an independent measure of ambulatory function in both stages of ambulation. The 6MWT may provide a quantitative, simple, and inexpensive outcome measure of walking capacity for early stage clinical trials in ambulatory patients with ALS.

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis

ABSTRACTIntroduction: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid.Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients.Expert opinion: The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant. The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

Cumulative Distribution of Amyotrophic Lateral Sclerosis Functional Rating Scale– Revised (ALSFRS-R) Scores in a Phase 3 Study of Edaravone (MCI-186) for the Treatment of Amyotrophic Lateral Sclerosis (ALS): A Posthoc Assessment (P5.110)

Cumulative Distribution of Amyotrophic Lateral Sclerosis Functional Rating Scale– Revised (ALSFRS-R) Scores in a Phase 3 Study of Edaravone (MCI-186) for the Treatment of Amyotrophic Lateral Sclerosis (ALS): A Posthoc Assessment (P5.110)

Edaravone (MCI-186) for the Treatment of Amyotrophic Lateral Sclerosis (ALS): A Posthoc Analysis of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) by Domain and Individual Items (P3.130)

Edaravone (MCI-186) for the Treatment of Amyotrophic Lateral Sclerosis (ALS): A Posthoc Analysis of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) by Domain and Individual Items (P3.130)

Quantitative Labial, Tongue Speech and Swallowing Rate Measurements at Diagnosis Correlate with ALS Functional Rating Scale – Revised (ALSFRS-R) Bulbar Subscore and Bulbar Subscore Item Scores – Effect of Nuedexta on Speech and Swallowing (P3.132)

Quantitative Labial, Tongue Speech and Swallowing Rate Measurements at Diagnosis Correlate with ALS Functional Rating Scale – Revised (ALSFRS-R) Bulbar Subscore and Bulbar Subscore Item Scores – Effect of Nuedexta on Speech and Swallowing (P3.132)

Predicting functional decline and survival in amyotrophic lateral sclerosis.

BackgroundBetter predictors of amyotrophic lateral sclerosis disease course could enable smaller and more targeted clinical trials. Partially to address this aim, the Prize for Life foundation collected de-identified records from amyotrophic lateral sclerosis sufferers who participated in clinical trials of investigational drugs and made them available to researchers in the PRO-ACT database.MethodsIn this study, time series data from PRO-ACT subjects were fitted to exponential models. Binary classes for decline in the total score of amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) (fast/slow progression) and survival (high/low death risk) were derived. Data was segregated into training and test sets via cross validation. Learning algorithms were applied to the demographic, clinical and laboratory parameters in the training set to predict ALSFRS-R decline and the derived fast/slow progression and high/low death risk categories. The performance of predictive models was assessed by cross-validation in the test set using Receiver Operator Curves and root mean squared errors.ResultsA model created using a boosting algorithm containing the decline in four parameters (weight, alkaline phosphatase, albumin and creatine kinase) post baseline, was able to predict functional decline class (fast or slow) with fair accuracy (AUC = 0.82). However similar approaches to build a predictive model for decline class by baseline subject characteristics were not successful. In contrast, baseline values of total bilirubin, gamma glutamyltransferase, urine specific gravity and ALSFRS-R item score—climbing stairs were sufficient to predict survival class.ConclusionsUsing combinations of small numbers of variables it was possible to predict classes of functional decline and survival across the 1–2 year timeframe available in PRO-ACT. These findings may have utility for design of future ALS clinical trials.

Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis.

A major hurdle in the development of effective treatments for amyotrophic lateral sclerosis (ALS) has been the lack of robust biomarkers for use as clinical trial endpoints. Neurochemical profiles obtained in vivo by high field proton magnetic resonance spectroscopy (1H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous 1H-MRS studies in ALS have produced conflicting findings regarding alterations in the levels of neurochemical markers such as glutamate (Glu) and myo-inositol (mIns). Furthermore, very few studies have investigated the neurochemical abnormalities associated with ALS early in its course. In this study, we measured neurochemical profiles using single-voxel 1H-MRS at 7T (T) and glutathione (GSH) levels using edited MRS at 3T in 19 subjects with ALS who had relatively high functional status [ALS Functional Rating Scale-Revised (ALSFRS-R) mean ± SD = 39.8 ± 5.6] and 17 healthy controls. We observed significantly lower total N-acetylaspartate over mIns (tNAA/mIns) ratio in the motor cortex and pons of subjects with ALS versus healthy controls. No group differences were detected in GSH at 3 and 7T. In subjects with ALS, the levels of tNAA, mIns, and Glu in the motor cortex were dependent on the extent of disease represented by El Escorial diagnostic subcategories. Specifically, combined probable/definite ALS had lower tNAA than possible ALS and controls (both p = 0.03), higher mIns than controls (p < 0.01), and lower Glu than possible ALS (p < 0.01). The effect of disease stage on MRS-measured metabolite levels may account for dissimilar findings among previous 1H-MRS studies in ALS.

The diagnostic utility of patient-report and speech-language pathologists’ ratings for detecting the early onset of bulbar symptoms due to ALS

Objective: This study aimed to determine the diagnostic utility of clinician speech ratings and patient self-report for detecting early bulbar changes associated with amyotrophic lateral sclerosis (ALS), compared to instrumentation-based speech measures.Methods: Thirty-six individuals with ALS and 17 healthy control participants were included. Patients’ awareness of early bulbar motor involvement was assessed using self-reported scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Clinicians’ detection of early bulbar motor involvement was assessed through perceptual speech ratings by two experienced speech-language pathologists. Participants with ALS were grouped as ‘bulbar pre-symptomatic’ or ‘bulbar symptomatic’ based on self-report and clinician ratings, and compared to healthy controls on six instrumentation-based speech measures. ROC analysis was used to compare the sensitivity and specificity of perceptual and instrumentation-based measures for detecting bulbar changes in pre-symptomatic individuals.Results: Early bulbar changes that were documented using instrumentation-based measures were undetected by both patients and clinicians. ROC analyses indicated that instrumentation-based measures outperformed clinicians’ scaled severity ratings, and that percent pause time was the best measure for differentiating healthy controls from bulbar pre-symptomatic individuals with ALS.Conclusions: Findings suggested that instrumentation-based measures of speech may be necessary for early detection of bulbar changes due to ALS.

Fixed dynamometry is more sensitive than vital capacity or ALS rating scale.

Improved outcome measures are essential to efficiently screen the growing number of potential amyotrophic lateral sclerosis (ALS) therapies. This longitudinal study of 100 (70 male) participants with ALS compared Accurate Test of Limb Isometric Strength (ATLIS), using a fixed, wireless load cell, with ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC). Participants enrolled at 5 U.S. sites. Data were analyzed from 66 participants with complete ATLIS, ALSFRS-R, and VC data over at least 3 visits. Change in ATLIS was less variable both within- and among-person than change in ALSFRS-R or VC. Additionally, participants who had normal ALSFRS-R arm and leg function averaged 12 to 32% below expected strength values measured by ATLIS. ATLIS was more sensitive to change than ALSFRS-R or VC and could decrease sample size requirements by approximately one-third. The ability of ATLIS to detect prefunctional change has potential value in early trials. Muscle Nerve 56: 710-715, 2017.

Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS.

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3months, and 19 patients at 0, 3 and 6months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p<0.05), and peroneal nerve (p<0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p<0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R=0.75, p<0.001) and peroneal nerves (R=0.52, p=0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R=0.48, p=0.002) and peroneal nerve (R=0.39, p=0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R=0.38, p=0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R=0.44, p=0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.

Urinary p75ECD: A prognostic, disease progression, and pharmacodynamic biomarker in ALS.

Objective:To evaluate urinary neurotrophin receptor p75 extracellular domain (p75ECD) levels as disease progression and prognostic biomarkers in amyotrophic lateral sclerosis (ALS).Methods:The population in this study comprised 45 healthy controls and 54 people with ALS, 31 of whom were sampled longitudinally. Urinary p75ECD was measured using an enzyme-linked immunoassay and validation included intra-assay and inter-assay coefficients of variation, effect of circadian rhythm, and stability over time at room temperature, 4°C, and repeated freeze-thaw cycles. Longitudinal changes in urinary p75ECD were examined by mixed model analysis, and the prognostic value of baseline p75ECD was explored by survival analysis.Results:Confirming our previous findings, p75ECD was higher in patients with ALS (5.6 ± 2.2 ng/mg creatinine) compared to controls (3.6 ± 1.4 ng/mg creatinine, p < 0.0001). Assay reproducibility was high, with p75ECD showing stability across repeated freeze-thaw cycles, at room temperature and 4°C for 2 days, and no diurnal variation. Urinary p75ECD correlated with the revised ALS Functional Rating Scale at first evaluation (r = −0.44, p = 0.008) and across all study visits (r = −0.36, p < 0.0001). p75ECD also increased as disease progressed at an average rate of 0.19 ng/mg creatinine per month (p < 0.0001). In multivariate prognostic analysis, bulbar onset (hazard ratio [HR] 3.0, p = 0.0035), rate of disease progression from onset to baseline (HR 4.4, p < 0.0001), and baseline p75ECD (HR 1.3, p = 0.0004) were predictors of survival.Conclusions:The assay for urinary p75ECD is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75ECD provides prognostic information and is currently the only biological fluid–based biomarker of disease progression.

Evaluating the levels of CSF and serum factors in ALS.

ObjectivesThe aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis.MethodsSerum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS‐r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model.ResultsA total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP‐1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP‐1 levels were associated with worse disease severity and faster progression, and the IFN‐γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN‐γ in the CSF had shorter overall survival.ConclusionsWe demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.

Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis

Objective: To assess safety and define efficacy measures of hepatocyte growth factor (HGF) DNA plasmid, VM202, administered by intramuscular injections in patients with amyotrophic lateral sclerosis (ALS).Methods: Eighteen participants were treated with VM202 administered in divided doses by injections alternating between the upper and lower limbs on d 0, 7, 14, and 21. Subjects were followed for nine months to evaluate possible adverse events. Functional outcome was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) as well as by serially measuring muscle strength, muscle circumference, and forced vital capacity.Results: Seventeen of 18 participants completed the study. All participants tolerated 64 mg of VM202 well with no serious adverse events (SAE) related to the drug. Twelve participants reported 26 mild or moderate injection site reactions. Three participants experienced five SAEs unrelated to VM202. One subject died from respiratory insufficiency secondary to ALS progression.Conclusions: Multiple intramuscular injection of VM202 into the limbs appears safe in ALS subjects. Future trials with retreatment after three months will determine whether VM202 treatment alters the long-term course of ALS.

Vitamin D in amyotrophic lateral sclerosis

Vitamin D supplementation has been proposed as a potential treatment to delay amyotrophic lateral sclerosis (ALS) progression. The aims of this study were to compare retrospectively vitamin D blood levels in ALS patients with those in healthy subjects; to correlate vitamin D blood levels with clinical functions in patients; and to evaluate whether administration of vitamin D could modify the clinical progression of the disease. Vitamin D blood levels were evaluated in 57ALS patients and in 57 healthy subjects. In the ALS patients the following clinical variables were evaluated every 3 months: Medical Research Council scale (MRC) score; revised ALS functional rating scale (ALSFRS-R) score; forced vital capacity (FVC). Twentyfour patients were treated with high doses of cholecalciferol. No significant differences were found between the vitamin D blood levels in the ALS patients (18.8 ± 12.2) and the healthy subjects (20.7 ± 10.1). The vitamin D levels in the ALS patientsdid not correlate with recorded clinical parameters. No clinical differences in terms of ALSFRS-R, MRC or FVC were found between the treated and the untreated patients over time. In ALS, as in other chronic neurological diseases, levels of vitamin D in blood appeared reduced, but no difference was found between the levels in ALS patients and in healthy subjects. Oral vitamin D supplementation in ALS patients was not associated with better prognosis in comparison with untreated ALS patients. Further prospective controlled studies are needed to clarify the effect of vitamin D on the progression of ALS disease.

Correlation between Forced Vital Capacity and Slow Vital Capacity for the assessment of respiratory involvement in Amyotrophic Lateral Sclerosis: a prospective study

Introduction: Slow vital capacity (SVC) and forced vital capacity (FVC) are the most frequent used tests evaluating respiratory function in amyotrophic lateral sclerosis (ALS). No previous study has determined their interchangeability.Objective: To evaluate SVC-FVC correlation in ALS.Methods: Consecutive definite/probable ALS and primary lateral sclerosis (PLS) patients (2000-2014) in whom respiratory tests were performed at baseline/4-6months later were included. All were evaluated with revised ALS functional rating scale, the ALSFRS respiratory (R-subscore) and bulbar subscores, SVC, FVC, maximal inspiratory (MIP) and expiratory (MEP) pressures. SVC-FVC correlation was analysed by Pearson product-moment correlation test. Paired t-test compared baseline/follow-up values. Multilinear regression analysis modelled the relationship between tested variables.Results: We included 592 ALS (332 men, mean onset age 62.6 ± 11.8 years, mean disease duration 15.4 ± 15 months) and 19 PLS (11 men, median age 54 years, median disease duration 5.5 years) patients. SVC and FVC predicted values decreased 2.15%/month and 2.08%/month, respectively. FVC and SVC were strongly correlated. Both were strongly correlated with MIP and MEP and moderately correlated with R-subscore for the all population and spinal-onset patients, but weakly correlated for bulbar-onset patients.Conclusions: FVC and SVC were strongly correlated and declined similarly. This correlation was preserved in bulbar-onset ALS and in spastic PLS patients.

The measurement and estimation of total energy expenditure in Japanese patients with ALS: a doubly labelled water method study

Appropriate nutritional therapy has not been established for patients with amyotrophic lateral sclerosis (ALS). Our objective was to measure the total energy expenditure (TEE) and determine an equation to estimate the energy requirements for Japanese patients with ALS. Twenty-six Japanese patients with ALS participated in the study. The TEE was measured using the doubly labelled water (DLW) method for a 14-day period. Using a range of clinical parameters and multiple regression analyses, we determined an adequate equation to calculate TEE. Results showed that the median value of total energy intake (TEI) was 1581 (interquartile 1278–1782) kcal/d. TEE and TEE/body weight were 1628 kcal/d (1352–1865) and 31.3 kcal/kg (29.2–34.4), respectively. The ratio of TEE/estimated TEE by the Harris-Benedict equation was 1.14 (1.09–1.26). The difference between TEI and TEE was –63 kcal (–221 – 122), and 15 patients (57.7%) showed a negative balance. From regression analyses, we determined an equation to estimate TEE using the resting metabolic rate estimated by the Harris-Benedict equation (RMR-HB) and scores of the revised ALS Functional Rating Scale (ALSFRS-R): TEE = (1.67 × RMR-HB) + (11.8 × ALSFRS-R) – 680 (p < 0.0001). In conclusion, energy expenditure of Japanese patients with ALS was higher than expected, and we proposed a preliminary equation to estimate TEE for future nutritional intervention.

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Background We are interested in how to optimise care for people with motor neurone disease (MND) who are on non-invasive ventilation (NIV) and whether technology can contribute. We have previously developed a respiratory question set for telemonitoring to complement the monitoring of continuous overnight oximetry and patient ventilator interactions (PVI). Objectives We wished to examine whether proactive management was feasible, determine the work generated for the clinical team and the impact on the maintenance of ventilation. Methods Ten ventilated patients (male=6; mean age=61yrs; median illness duration=14 months; median NIV usage=11 months) were recruited and followed for 6 months. Participants used a telemonitoring device (Careportal®) to complete the respiratory questions; nocturnal pulse oximetry and PVI were also assessed weekly. Although monitored, patients were told to contact their general practitioner (GP) for emergencies. Revised ALS functional rating scale (ALSFRS-R) and Hospital Anxiety and Depression Scale (HADS) were completed three-monthly. Non-parametric tests were used to identify changes in oxygen saturation levels (SpO2), PVI, ALSFRS-R, and HADS over the trial period. Results In total, 118 telemonitoring question alerts led to 40 interventions in 8 patients (equipment provision=16, treatment adjustment=15, direct reviews=8, referral=1), these were needed despite 5 having had recent routine outpatient review. Twenty-four interventions were triggered by the answers to the respiratory questions, 8 were requested by patients through Careportal®, 5 had pressure adjustments to correct suboptimal nocturnal oximetry and 3 were follow-up interventions. Three patients made unscheduled GP contacts and one of them was hospitalised with pneumonia, despite being on antibiotics. Amongst PVI data, minute ventilation (MV) was maintained; baseline mean=6.32 l/min (SD=1.81) and endpoint mean=7.2 l/min (SD=2.64). Inspiratory positive airway pressure (IPAP) [7 patients had alterations] and NIV usage time changed significantly; baseline IPAP cmH2O mean=16.97 (SD=4.2) and end point mean=20.53 (SD=5.46;p=.004); baseline NIV usage mean=8.55hrs (SD=3.32) and endpoint mean=11.45hrs (SD=3.55;p=.006). ALSFRS-R scores deteriorated: baseline mean =22.9 (SD=10.9) and end point mean =18.8 (SD=10.19;p=.008). HADS scores for anxiety did not change from baseline (mean=4.5; SD=3.37) to end point (mean=3.9; SD=3.07) or for depression from baseline (mean=6.3; SD=3.47) to endpoint (mean=8.3; SD=4.85). Discussion and conclusions We found weekly telemonitoring to be feasible. Optimisation of SpO2 levels was enabled and ventilation was maintained. The bespoke questions triggered 60% of the interventions, highlighting the importance of symptom review in addition to physiological or PVI measurements. Maintained HADS suggest no adverse effect of telemonitoring, this and whether it is perceived as useful is being explored through qualitative work. This approach may replace some traditional reviews, linking the patient effectively to the care team. Further study should be conducted to examine its impact on the holistic management of this patient group including health economics and outcomes.

Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS.