| 11. |
- Nandedkar, Sanjeev D., et al.
(författare)
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Motor unit number index : Guidelines for recording signals and their analysis
- 2018
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Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 58:3, s. 374-380
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study proposes guidelines for motor unit number index (MUNIX) recording and analysis. Methods: MUNIX was measured in control participants and in patients with amyotrophic lateral sclerosis. Changes in MUNIX values due to E1 electrode position, number of surface electromyography interference pattern (SIP) epochs, SIP epoch duration, force of contraction, and outlier data points were investigated. Results: MUNIX depends on optimized compound muscle action potential (CMAP) amplitude. Individual muscles showed variations when the number of epochs was low or when the SIP duration was short. Longer SIP duration allowed better recognition of artifacts. MUNIX results were affected by SIP values at all force levels but was more affected when SIP area was low. Discussion: We recommend changing the E1 electrode position to maximize CMAP amplitude. Twenty or more SIP signals of 500-ms duration should be recorded by using force levels ranging from slight to maximum. Traces should be reviewed to identify and exclude signals with tremor or solitary spikes.
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| 12. |
- Neuwirth, Christoph, et al.
(författare)
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Implementing Motor Unit Number Index (MUNIX) in a large clinical trial : Real world experience from 27 centres
- 2018
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Ingår i: Clinical Neurophysiology. - : Elsevier. - 1388-2457 .- 1872-8952. ; 129:8, s. 1756-1762
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters.METHODS: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated.RESULTS: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential.CONCLUSION: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed.SIGNIFICANCE: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process.
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| 13. |
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| 14. |
- Neuwirth, Christoph, et al.
(författare)
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Motor Unit Number Index (MUNIX) : A novel neurophysiological marker for neuromuscular disorders; test-retest reliability in healthy volunteers
- 2011
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 122:9, s. 1867-1872
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the intra-rater and inter-rater test-retest reliability of the Motor Unit Number Index (MUNIX) in healthy subjects in a multicentre setting. Methods: Six study centres applied the MUNIX technique in 66 healthy subjects. Five to six muscles (biceps brachii, BB; abductor digiti minimi, ADM; abductor pollicis brevis, APB; tibialis anterior, TA; extensor digitorum brevis, EDB and abductor hallucis, AH) were measured in each volunteer four times by two independent examiners. Results: The method was easy to perform and well tolerated. The intraclass correlation coefficient (ICC) varied between centres and muscles. Intra-rater reliability was greatest for the AH (ICC 0.83) and EDB (ICC 0.81). Inter-rater reliability was greatest for the AH (ICC 0.69) and ADM muscles (ICC 0.69). The most critical muscle was the APB muscle (ICC 0.52, total variability). This was mostly due to variability in the compound muscle action potential (CMAP) measurements. MUNIX values of the APB, ADM and TA fell into the same range as in other motor unit number estimation (MUNE) studies. Conclusion: MUNIX measurements in multiple muscles show good inter- and intra-rater reliability in healthy subjects. CMAP amplitude must be controlled to optimize reliability. Significance: Results suggest that MUNIX could serve as a reliable marker for motor neuron loss in diseases like amyotrophic lateral sclerosis. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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| 15. |
- Neuwirth, Christoph, et al.
(författare)
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Motor Unit Number Index (MUNIX) : A novel neurophysiological technique to follow disease progression in amyotrophic lateral sclerosis
- 2010
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Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 42:3, s. 379-384
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Tidskriftsartikel (refereegranskat)abstract
- Motor unit number estimation techniques in amyotrophic lateral sclerosis (ALS) patients are technically challenging and time-consuming. The Motor Unit Number Index (MUNIX) is a novel technique based on surface-EMG recordings and requires only 3-5 minutes per muscle. The objective was to explore the feasibility of longitudinal MUNIX measurements in ALS patients. In seven patients enrolled in a clinical trial, eight muscles were studied every 2 months for up to 15 months in addition to the revised ALS-functional rating scale, slow vital capacity, and compound muscle action potentials. The method was well tolerated and easy to perform. Initial MUNIX measures were significantly reduced compared to controls (487 +/- 194 vs. 1459 113; P < 0.001). Relative drop from baseline paralleled the clinical course and was greater than the drop of other markers of disease progression. MUNIX measurements in multiple muscles are suitable for serial neurophysiologic investigations in ALS. Further longitudinal data are needed for reliability validation.
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| 16. |
- Neuwirth, Christoph, et al.
(författare)
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Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis
- 2017
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Ingår i: Clinical Neurophysiology. - : ELSEVIER IRELAND LTD. - 1388-2457 .- 1872-8952. ; 128:3, s. 495-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles. Methods: Three centres measured MUNIX in 49 ALS patients every three months in six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis, abductor hallucis) on the less affected side. The decline of MUNIX in initially non-wasted, clinically strong muscles (manual muscle testing, MMT grade 5) was analysed before and after onset of weakness. Results: In 49 subjects, 151 clinically strong muscles developed weakness and were included for analysis. The average monthly relative loss of MUNIX was 5.0% before and 5.6% after onset of weakness. This rate of change was significantly higher compared to ALS functional rating scale (ALSFRS-R) and compound muscle action potential (CMAP) change over 12 months prior to the onset of muscle weakness (p = 0.024). Conclusion: MUNIX is an electrophysiological marker that detects lower motor neuron loss in ALS, before clinical weakness becomes apparent by manual muscle testing. Significance: This makes MUNIX a good biomarker candidate for disease progression and possibly pharmacodynamics responds.
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| 17. |
- Neuwirth, Christoph, et al.
(författare)
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Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX) : a 15-month longitudinal multicentre trial
- 2015
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11, s. 1172-1179
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Tidskriftsartikel (refereegranskat)abstract
- Background Motor Unit Number Index (MUNIX) is a novel neurophysiological measure that provides an index of the number of functional lower motor neurons in a given muscle. So far its performance across centres in patients with amyotrophic lateral sclerosis (ALS) has not been investigated. Objective To perform longitudinal MUNIX recordings in a set of muscles in a multicentre setting in order to evaluate its value as a marker of disease progression. Methods Three centres applied MUNIX in 51 ALS patients over 15 months. Six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor dig. brevis, abductor hallucis) were measured every 3 months on the less affected side. The decline between MUNIX and ALSFRS-R was compared. Results 31 participants reached month 12. For all participants, ALSFRS-R declined at a rate of 2.3%/month. Using the total score of all muscles, MUNIX declined significantly faster by 3.2%/month (p <= 0.02). MUNIX in individual muscles declined between 2.4% and 4.2%, which differed from ASLFRS-R decline starting from month 3 (p <= 0.05 to 0.002). Subgroups with bulbar, lower and upper limb onset showed different decline rates of ALSFRS-R between 1.9% and 2.8%/month, while MUNIX total scores showed similar decline rates over all subgroups. Mean intraclass correlation coefficient for MUNIX intra-rater reliability was 0.89 and for inter-rater reliability 0.80. Conclusion MUNIX is a reliable electrophysiological biomarker to track lower motor neuron loss in ALS.
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| 18. |
- Nordin, Angelica, et al.
(författare)
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Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation : a large multinational screening study
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 18:3-4, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele. In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
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| 19. |
- Stålberg, Erik, et al.
(författare)
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Standards for quantification of EMG and neurography
- 2019
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 130:9, s. 1688-1729
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Forskningsöversikt (refereegranskat)abstract
- This document is an update and extension of ICCN Standards published in 1999. It is the consensus of experts on the current status of EMG and Neurography methods. A panel of authors from different countries with different approach to routines in neurophysiological methods was chosen based on their particular interest and previous publications. Each member of the panel submitted a section on their particular area of interest and these submissions were circulated among the panel members for edits and comments. This process continued until a consensus was reached. The document covers EMG topics such as conventional EMG, Macro EMG, applications of surface EMG and electrical impedance myography. Single Fiber EMG is not included, since it is the topic in a separate IFCN document. A neurography section covers topics such as motor and sensory neurography, F wave recordings, H-reflex, short segment recordings, CMAP scan and motor unit number methods. Other sections cover repetitive nerve stimulation and Pediatric electrodiagnostic testing. Each method includes a description of methodologies, pitfalls, and the use of reference values. Clinical applications accompany some of these sections.
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| 20. |
- Tazelaar, Gijs H.P., et al.
(författare)
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Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis
- 2023
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 122, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors. To explore the contribution of somatic mutations and/or epigenetic changes to disease risk, we performed whole genome sequencing and methylation analyses using samples from multiple tissues on a cohort of 26 monozygotic twins discordant for ALS, followed by in-depth validation and replication experiments. The results of these analyses implicate several mechanisms in ALS pathophysiology, which include a role for de novo mutations, defects in DNA damage repair and accelerated aging.
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