Amyotrophic lateral sclerosis diagnostic index

ObjectiveThe aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).MethodsA prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Patients were randomly assigned to a training (75%) and a test (25%) cohort. The ALSDI was developed in the training cohort and its diagnostic utility was subsequently assessed in the test cohort.ResultsA total of 407 patients were recruited, with 305 patients subsequently diagnosed with ALS and 102 with a non-ALS mimicking disorder. The ALSDI reliably differentiated ALS from neuromuscular disorders in the training cohort (area under the curve 0.92, 95% confidence interval 0.89–0.95), with ALSDI ≥4 exhibiting 81.6% sensitivity, 89.6% specificity, and 83.5% diagnostic accuracy. The ALSDI diagnostic utility was confirmed in the test cohort (area under the curve 0.90, 95% confidence interval 0.84–0.97), with ALSDI ≥4 exhibiting 83.3% sensitivity, 84% specificity, and 83.5% diagnostic accuracy. In addition, the diagnostic utility of the ALSDI was confirmed in patients who were Awaji negative at recruitment and in those exhibiting a predominantly lower motor neuron phenotype.ConclusionThe ALSDI reliably differentiates ALS from mimicking disorders at an early stage in the disease process.Classification of evidenceThis study provides Class I evidence that for patients with suspected ALS, the ALSDI distinguished ALS from neuromuscular mimicking disorders.

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Non-invasive measurement of fasciculation frequency demonstrates diagnostic accuracy in amyotrophic lateral sclerosis

Brain Communications ◽

10.1093/braincomms/fcaa141 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Arina Tamborska ◽

James Bashford ◽

Aidan Wickham ◽

Raquel Iniesta ◽

Urooba Masood ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Confidence Interval ◽

Biceps Brachii ◽

Delayed Diagnosis ◽

Area Under The Curve ◽

Motor Neuropathy ◽

Healthy Individuals ◽

Non Invasive ◽

Lateral Sclerosis ◽

Invasive Measurement

Abstract Delayed diagnosis of amyotrophic lateral sclerosis prevents early entry into clinical trials at a time when neuroprotective therapies would be most effective. Fasciculations are an early hallmark of amyotrophic lateral sclerosis, preceding muscle weakness and atrophy. To assess the potential diagnostic utility of fasciculations measured by high-density surface electromyography, we carried out 30-min biceps brachii recordings in 39 patients with amyotrophic lateral sclerosis, 7 patients with benign fasciculation syndrome, 1 patient with multifocal motor neuropathy and 17 healthy individuals. We employed the surface potential quantification engine to compute fasciculation frequency, fasciculation amplitude and inter-fasciculation interval. Inter-group comparison was assessed by Welch’s analysis of variance. Logistic regression, receiver operating characteristic curves and decision trees discerned the diagnostic performance of these measures. Fasciculation frequency, median fasciculation amplitude and proportion of inter-fasciculation intervals <100 ms showed significant differences between the groups. In the best-fit regression model, increasing fasciculation frequency and median fasciculation amplitude were independently associated with the diagnosis of amyotrophic lateral sclerosis. Fasciculation frequency was the single best measure predictive of the disease, with an area under the curve of 0.89 (95% confidence interval 0.81–0.98). The cut-off of more than 14 fasciculation potentials per minute achieved 80% sensitivity (95% confidence interval 63–90%) and 96% specificity (95% confidence interval 78–100%). In conclusion, non-invasive measurement of fasciculation frequency at a single time-point reliably distinguished amyotrophic lateral sclerosis from its mimicking conditions and healthy individuals, warranting further research into its diagnostic applications.

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Critical Review of Complementary and Alternative Medicine Use in Amyotrophic Lateral Sclerosis: Prevalence and Users’ Profile, Decision-Making, Information Seeking, and Disclosure in the Face of a Lack of Efficacy

Neurodegenerative Diseases ◽

10.1159/000492946 ◽

2018 ◽

Vol 18 (4) ◽

pp. 225-232 ◽

Cited By ~ 2

Author(s):

Jon Adams ◽

Michael Lee ◽

Wenbo Peng

Keyword(s):

Decision Making ◽

Amyotrophic Lateral Sclerosis ◽

Alternative Medicine ◽

Complementary And Alternative Medicine ◽

Information Seeking ◽

Disease Process ◽

Cam Use ◽

Als Patients ◽

Lateral Sclerosis ◽

Complementary And Alternative

Background: Despite a lack of evidence of clinical efficacy for complementary and alternative medicine (CAM) use in amyotrophic lateral sclerosis (ALS), these medicines remain popular around the world. Objective: To examine the prevalence and cost of CAM use in ALS and CAM users’ profile, decision-making, information seeking, and disclosure among ALS patients. Methods: A comprehensive literature search was conducted of MEDLINE, CINAHL/SCOPUS, and AMED databases from their inception to April 2018. This review followed PRISMA guidelines and employed a quality scoring system to assess the included papers. Results: Seven papers met the inclusion criteria and were thematically analysed. ALS patients utilized a range of CAM therapies and/or products, with acupuncture and vitamins being the most frequently reported. CAM modalities were often employed concurrently with conventional medications throughout the disease process. Although some ALS patients reported positive experience regarding CAM use, many were reluctant to disclose their CAM use to their clinicians. Research focusing on CAM use in ALS remains ad hoc and restricted to only a few countries. The rigour and quality of this research field to date has been varied, predominantly drawing upon regional/localized data and failing to report CAM users’ characteristics. Conclusion: A proportion of ALS patients report utilizing CAM concurrently with conventional treatments. Such use, set amidst a dearth of evidence for the efficacy of CAM in ALS, poses potential direct and indirect risks to patient care, and medical providers should be mindful of and enquire about CAM use when treating ALS patients.

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Appearance, phenomenology and diagnostic utility of the split hand in amyotrophic lateral sclerosis

Neurodegenerative Disease Management ◽

10.2217/nmt.11.60 ◽

2011 ◽

Vol 1 (6) ◽

pp. 457-462 ◽

Cited By ~ 10

Author(s):

Parvathi Menon ◽

Matthew C Kiernan ◽

Steve Vucic

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Diagnostic Utility ◽

Lateral Sclerosis

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CSF chitinase proteins in amyotrophic lateral sclerosis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-320442 ◽

2019 ◽

Vol 90 (11) ◽

pp. 1215-1220 ◽

Cited By ~ 14

Author(s):

Alexander G Thompson ◽

Elizabeth Gray ◽

Alexander Bampton ◽

Dominika Raciborska ◽

Kevin Talbot ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Area Under The Curve ◽

Neuronal Loss ◽

Progression Rate ◽

Healthy Controls ◽

Reactive Protein ◽

Classifier Performance ◽

Disease Progression Rate ◽

Csf Levels ◽

Lateral Sclerosis

ObjectiveTo evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels of the chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) and Chitinase-3-like protein 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS).MethodsCSF levels of CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) and C-reactive protein were measured by ELISA in a longitudinal cohort of patients with ALS (n=82), primary lateral sclerosis (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25) and asymptomatic carriers of ALS-causing genetic mutations (AGC; n=5).ResultsCSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p<0.001) and ALS-mimics (CHIT1, p<0.001; CHI3L1, p=0.017; CHI3L2, p<0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p<0.001). Chitinase levels were similar in AGCs and healthy controls. Chitinase proteins distinguished ALS from healthy controls (area under the curve (AUC): CHIT1 0.92; CHI3L1 0.80; CHI3L2 0.90), mimics (AUC: CHIT1 0.84; CHI3L1 0.73; CHI3L2 0.88) and, to a lesser extent, PLS (AUC: CHIT 0.73; CHI3L1 0.51; CHI3L2 0.82) but did not outperform pNFH. CHIT1 and CHI3L2 correlated with disease progression rate (Pearson’s r=0.49, p<0.001; r=0.42, p<0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (r=−0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.ConclusionsCSF chitinase proteins may have limited value as independent diagnostic and stratification biomarkers in ALS, but offer a window into non-autonomous mechanisms of motor neuronal loss in ALS, specifically in assessing response to therapies targeting neuroinflammatory pathways.

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O54: Diagnostic utility of cortical hyperexcitability in amyotrophic lateral sclerosis

Clinical Neurophysiology ◽

10.1016/s1388-2457(14)50157-5 ◽

2014 ◽

Vol 125 ◽

pp. S44

Author(s):

N. Geevasinga ◽

P. Menon ◽

C. Yiannikas ◽

M. Kiernan ◽

S. Vucic

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Diagnostic Utility ◽

Cortical Hyperexcitability ◽

Lateral Sclerosis

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Teaching an Old Dog New Tricks: Serum Troponin T as a Biomarker in Amyotrophic Lateral Sclerosis

10.1101/2021.02.15.21251783 ◽

2021 ◽

Author(s):

Sergio Castro-Gomez ◽

Barbara Radermacher ◽

Pawel Tacik ◽

Sandra R. Mirandola ◽

Michael T. Heneka ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Troponin I ◽

Troponin T ◽

Case Reports ◽

Neuromuscular Disorders ◽

University Hospital ◽

Biological Origin ◽

Muscle Involvement ◽

Als Patients ◽

Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Diagnosis, management and therapeutic trials are hampered by a lack of informative biomarkers. Troponins (Tn) are components of skeletal and cardiac muscles. Acute elevation of cardiac isoforms of troponin I (cTnI) and T (cTnT) in serum indicates myocardial injury. Case reports suggested that serum levels of cTnT, but not cTnI are chronically elevated in ALS and other neuromuscular disorders.Using standard clinical laboratory methodologies we studied serum troponin levels in a multicentric cross-sectional cohort of 75 ALS patients and sixty controls (DESCRIBE-ALS cohort) and in a real-world cohort of 179 consecutive patients from our ALS clinic at the University Hospital Bonn.We found that serum cTnT, is elevated in >60% of ALS patients while cTnI is always normal. Serum cTnT levels increase over time and correlate with disease severity as measured with the revised ALS FRS score. There was no correlation with the phosphorylated neurofilament heavy chain (pNfH) levels in the cerebrospinal fluid. We propose that cTnT elevations in ALS are of non-cardiac origin and may serve as a proxy of lower motor neuron or skeletal muscle involvement. They potentially help to stratify patients according to lower motoneuron involvement. Further research will determine the biological origin of the cTnT elevation and its validity as a diagnostic and/or prognostic marker. Our finding also serves as a reminder to interpret cTnT with caution elevations in patients with neuromuscular diseases.

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Automatic amyotrophic lateral sclerosis detection using tunable Q-factor wavelet transform

IAES International Journal of Artificial Intelligence (IJ-AI) ◽

10.11591/ijai.v9.i4.pp744-756 ◽

2020 ◽

Vol 9 (4) ◽

pp. 744

Author(s):

Abdelouahad Achmamad ◽

Abdelali Belkhou ◽

Atman Jbari

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Wavelet Transform ◽

Nearest Neighbor ◽

Neuromuscular Disorders ◽

Computation Time ◽

Support Vector ◽

Q Factor ◽

K Nearest Neighbor ◽

Emg Signal ◽

Lateral Sclerosis

Early diagnosis of amyotrophic lateral sclerosis (ALS) based on electromyography (EMG) is crucial. The processing of a non-stationary EMG signal requires powerful multi-resolution methods. Our study analyzes and classifies the EMG signals. In the present work, we introduce a novel flexible method for classification of EMG signals using tunable Q-factor wavelet transform (TQWT). Different sub-bands generated by the TQWT technique were served to extract useful information related to energy and then the calculated features were selected using a filter selection (FS) method. The effectiveness of the feature selection step resulted not only in the improvement of classification performance but also in reducing the computation time of the classification algorithm. The selected feature subsets were used as inputs to multiple classifier algorithms, namely, k-nearest neighbor (k-NN), least squares support vector machine (LS-SVM) and random forest (RF) for automated diagnosis. The experimental results show better classification measures with k-NN classifier compared with LS-SVM and RF. The robustness of the classification task was tested using a ten-fold cross-validation method. The outcomes of our proposed approach can be exploited to aid clinicians in neuromuscular disorders detection.

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Altered Metabolic Profiles of the Plasma of Patients with Amyotrophic Lateral Sclerosis

Biomedicines ◽

10.3390/biomedicines9121944 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1944

Author(s):

Kuo-Hsuan Chang ◽

Chia-Ni Lin ◽

Chiung-Mei Chen ◽

Rong-Kuo Lyu ◽

Chun-Che Chu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Area Under The Curve ◽

Support Vector ◽

Therapeutic Effects ◽

Targeted Metabolomics ◽

Svm Algorithm ◽

Als Patients ◽

Normal Controls ◽

Lateral Sclerosis

Currently, there is no objective biomarker to indicate disease progression and monitor therapeutic effects for amyotrophic lateral sclerosis (ALS). This study aimed to identify plasma biomarkers for ALS using a targeted metabolomics approach. Plasma levels of 185 metabolites in 36 ALS patients and 36 age- and sex-matched normal controls (NCs) were quantified using an assay combining liquid chromatography with tandem mass spectrometry and direct flow injection. Identified candidates were correlated with the scores of the revised ALS Functional Rating Scale (ALSFRS-r). Support vector machine (SVM) learning applied to selected metabolites was used to differentiate ALS and NC subjects. Forty-four metabolites differed significantly between ALS and NC subjects. Significant correlations with ALSFRS-r score were seen in 23 metabolites. Six of them showing potential to distinguish ALS from NC—asymmetric dimethylarginine (area under the curve (AUC): 0.829), creatinine (AUC: 0.803), methionine (AUC: 0.767), PC-acyl-alkyl C34:2 (AUC: 0.808), C34:2 (AUC: 0.763), and PC-acyl-acyl C42:2 (AUC: 0.751)—were selected for machine learning. The SVM algorithm using selected metabolites achieved good performance, with an AUC of 0.945. In conclusion, our findings indicate that a panel of metabolites were correlated with disease severity of ALS, which could be potential biomarkers for monitoring ALS progression and therapeutic effects.

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Weakness of the Neck Muscles

10.1093/med/9780190661304.003.0010 ◽

2018 ◽

Author(s):

Aziz Shaibani

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Movement Disorders ◽

Cervical Dystonia ◽

Neuromuscular Disorders ◽

The Elderly ◽

Central Control ◽

Lateral Bending ◽

Flexion Extension ◽

Differential Involvement ◽

Lateral Sclerosis

The neck is furnished by tens of muscles for flexion, extension, lateral bending, and rotation. It carries a 10-pound head for at least two-thirds of every day. These muscles are under delicate central control, and they are subject to different central and peripheral malfunctions. Differential involvement of the neck flexors’ Vs extensors helps with the diagnosis of various neuromuscular disorders. Weakness of the cervical extensors leads to head drop, a troubling condition that is caused by many neuromuscular disorders. Movement disorders such as cervical dystonia and Parkinson disease lead to head drop, causing confusion with neuromuscular causes such as myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS). Head protrusion of the elderly (camptocormia) is a different entity.

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