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INTRODUCTION/AIMS: In adult spinal muscular atrophy (SMA), the motor unit number index (MUNIX) has been shown to be an useful electrophysiological biomarker. This study evaluated the feasibility and the clinical relevance of using the MUNIX technique for patients with pediatric SMA (Ped-SMA) and correlated MUNIX results with clinical scores. METHODS: Fourteen patients with type II Ped-SMA (11 females; median age 11 y [interquartile range (IQR), 4.8-17 y]) and 14 controls (nine females; median age 10.75 y [IQR, 6.5-13.4 y]) were enrolled and matched by sex, age, height, weight, and body mass index. Clinical examination included manual muscle testing, dynamometry (grasp and pinch), and motor function measure (MFM). The MUNIX technique was evaluated in the abductor digiti minimi (ADM) and abductor pollicis brevis (APB) on two sides when possible. RESULTS: In the patients with Ped-SMA, the MUNIX and compound muscle action potential (CMAP) amplitudes were significantly decreased and the motor size unit index (MUSIX) was significantly increased in the ADM and APB when compared to controls. The intraclass correlation coefficient was good for the intrarater variability of the CMAP amplitude, MUNIX, and MUSIX in the ADM (0.95, 0.83, and 0.89, respectively) and the APB (0.98, 0.96, and 0.94, respectively). The total CMAP amplitude correlated with the grasp and pinch scores (P < .05), and the MUNIX measurements correlated with the MFM scores. DISCUSSION: The MUNIX technique, which accurately estimated lower motor neuron loss and the number of remaining functional motor units, was shown to be a useful electrophysiological biomarker for disease progression and a potential biomarker for treatment response.
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Potenciais de Ação/fisiologia , Neurônios Motores/fisiologia , Recrutamento Neurofisiológico/fisiologia , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/fisiopatologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Atrofias Musculares Espinais da Infância/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
BACKGROUND: Previous research has described a neuroprotective effect of IGF-I, supporting neuronal survival, axon growth and proliferation of muscle cells. Therefore, the association between IGF-I concentration, muscle histology and electrophysiological markers in a cohort of patients with sarcopenia dares investigation. METHODS: Measurement of serum concentrations of IGF-I and binding partners, electromyographic measurements with the MUNIX (Motor Unit Number Index) method and muscle biopsies were performed in 31 patients with acute hip fracture older age 60 years. Molecular markers for denervation (neural cell adhesion molecule NCAM) and proliferation markers (Ki67) were assessed by immunofluorescence staining of muscle biopsy tissue. Skeletal muscle mass by bioelectrical impedance analysis and hand-grip strength were measured to assess sarcopenia status according to EWGSOP2 criteria. RESULTS: Thirty-one patients (20 women) with a mean age of 80.6 ± 7.4 years were included. Concentrations of IGF-I and its binding partners were significantly associated with sarcopenia (ß = - 0.360; p = 0.047) and MUNIX (ß = 0.512; p = 0.005). Further, expression of NCAM (ß = 0.380; p = 0.039) and Ki67 (ß = 0.424; p = 0.022) showed significant associations to IGF-I concentrations. CONCLUSIONS: The findings suggest a pathogenetic role of IGF-I in sarcopenia based on muscle denervation.
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Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Feminino , Força da Mão , Humanos , Fator de Crescimento Insulin-Like I , Músculo Esquelético/patologia , Regeneração , Sarcopenia/diagnósticoRESUMO
INTRODUCTION: We sought to evaluate the reproducibility of the motor unit number index (MUNIX) and MScanFit motor unit number estimation (MScan) when recording was performed over intrinsic hand muscles. METHODS: The compound muscle action potential (CMAP) amplitude, MUNIX, and MScan were measured from the abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digit minimi (ADM) muscles from 15 healthy volunteers on three different occasions. RESULTS: The reproducibility of CMAP amplitudes was excellent, with intraclass correlation coefficients (ICC) of 0.86 (APB), 0.90 (FDI), and 0.96 (ADM). Motor unit number index (ICCAPB 0.73, ICCFDI 0.85, ICCADM 0.85) and MScan (ICCAPB 0.86, ICCFDI 0.83, ICCADM 0.81) were highly reproducible across the three muscles. There were no significant correlations between MUNIX and MScan coefficients of variation (CV) and CMAP amplitude CVs. DISCUSSION: Reproducibility of MUNIX and MScan was not significantly different across the intrinsic hand muscles and was independent of CMAP amplitude variability.
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Potenciais de Ação/fisiologia , Mãos , Neurônios Motores/fisiologia , Músculo Esquelético/fisiologia , Adulto , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Neurônios Motores/citologia , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Pathogenesis in a subgroup of sarcopenic patients seems to be based on a reduced number of motor neurons. This study aimed at investigating the overlap between sarcopenia and neurodegeneration, as reflected by a low number of motor neurons in patients with Parkinsonian syndromes (PS). METHODS: The motor unit number index (MUNIX) of the hypothenar muscle was used to assess the number and size (MUSIX) of motor units (MUs) in patients with idiopathic Parkinson disease (iPD, n = 53), patients with atypical Parkinsonian syndrome (aPS, n = 21), and a control group (n = 30). Mean age of participants was 70.3 years and 54.1% were female. Skeletal muscle mass by bioelectrical impedance analysis, hand-grip strength and gait speed were measured. Based on these assessments, sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: Sarcopenia criteria were met by 10 patients with PS (13.5%). The study group had significantly lower MUNIX values than the control group (109 [SD ±39.1] vs. 129 [SD ±45.1]; p = 0.020) even after adjustment for age and sex. Three of the 5 sarcopenic iPD patients (75%) had pathological low MUNIX values (<80). DISCUSSION/CONCLUSION: Sarcopenia is a frequent comorbidity in PS. The pathologically low MUNIX values found in 75% of our sarcopenic iPD patients provides further support for the existence of a neurodegenerative overlap syndrome with a reduced number of MUs potentially leading to sarcopenia. This finding warrants further evaluation.
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Neurônios Motores/patologia , Transtornos Parkinsonianos/fisiopatologia , Sarcopenia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Alemanha , Força da Mão , Humanos , Masculino , Músculo Esquelético , Degeneração Neural/fisiopatologia , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/complicações , Sarcopenia/complicações , Velocidade de CaminhadaRESUMO
PURPOSE: The objective of this study was to assess whether artificial gravity attenuates any long-duration head-down 60 bed rest (HDBR)-induced alterations in motor unit (MU) properties. METHODS: Twenty-four healthy participants (16 men; 8 women; 26-54 years) underwent 60-day HDBR with (n = 16) or without (n = 8) 30 min artificial gravity daily induced by whole-body centrifugation. Compound muscle action potential (CMAP), MU number (MUNIX) and MU size (MUSIX) were estimated using the method of Motor Unit Number Index in the Abductor digiti minimi and tibialis anterior muscles 5 days before (BDC-5), and during day 4 (HDT4) and 59 (HDT59) of HDBR. RESULTS: The CMAP, MUNIX, and MUSIX at baseline did not change significantly in either muscle, irrespective of the intervention (p > 0.05). Across groups, there were no significant differences in any variable during HDBR, compared to BDC-5. CONCLUSION: Sixty days of HDBR with or without artificial gravity does not induce alterations in motor unit number and size in the ADM or TA muscles in healthy individuals.
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Repouso em Cama/efeitos adversos , Fibras Musculares Esqueléticas/fisiologia , Simulação de Ausência de Peso/efeitos adversos , Adulto , Repouso em Cama/métodos , Feminino , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
INTRODUCTION: The objective of this study was to evaluate a recently developed motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), as a measure of disease progression in amyotrophic lateral sclerosis (ALS) compared with compound muscle action potential (CMAP) amplitude and 2 traditional MUNE methods. METHODS: ALS patients were evaluated clinically using the ALS Functional Rating Scale-Revised (ALSFRS-R). MScan, multiple-point stimulation MUNE (MPS), and motor unit number index (MUNIX) were performed in the abductor pollicis brevis (APB) muscle at baseline (27 patients), 4 months (23 patients), and 8 months (16 patients). RESULTS: Of the 5 measures, MScan registered the largest decline (8.7% per month), compared with MPS (3.4%), MUNIX (4.8%), CMAP amplitude (2.0%), and ALSFRS-R (1.9%). Only MScan and ALSFRS-R registered significant decrements over 4 and 8 months. DISCUSSION: MScan may be useful as a sensitive, objective tool for quantifying motor unit loss in ALS. Muscle Nerve 59:82-87, 2019.
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Potencial Evocado Motor/fisiologia , Doença dos Neurônios Motores/fisiopatologia , Neurônios Motores/fisiologia , Músculo Esquelético/fisiopatologia , Idoso , Progressão da Doença , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Routine quantitative electromyography is used for the assessment of the presence of lower motor neurone involvement and its consequences, including primary denervation and compensatory reinnervation of muscle fibres. However, it is not useful for the assessment of the motor unit number reserve. The need for a valid biomarker to evaluate lower motor neurone disease progression in such diseases as amyotrophic lateral sclerosis, and for use in clinical trials, has led to a number of studies of the methods that allow assessment of the number of motor units. In this review, motor unit number estimation (MUNE) methods with incremental stimulation and the recently developed motor unit number index (MUNIX) method, along with their technical and clinical aspects, are presented as methods which reflect motor unit loss in neurogenic processes. These electrodiagnostic tests may allow a valuable assessment of disease progression and the efficacy of new therapeutic methods in clinical trials in diseases with lower motor neurone degeneration.
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Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Potenciais de Ação , Eletromiografia , Humanos , Músculo EsqueléticoRESUMO
INTRODUCTION: Our objective was to determine the utility of motor unit number index (MUNIX) and neurophysiological index (NI) as surrogate biomarkers of disease progression in limbs without clinical signs of lower motor neuron (LMN) involvement from patients with slowly progressive amyotrophic lateral sclerosis (ALS). METHODS: Patients with slowly progressive ALS and at least 1 clinically unaffected limb were prospectively enrolled. Clinical signs of LMN loss and results from hand-held dynamometer (HHD), revised ALS Functional Rating Scale (ALSFRS-R), mean-MUNIX (from 3 different muscles), and NI were longitudinally recorded. RESULTS: Eighteen patients with 43 presymptomatic muscles were evaluated. Twenty-seven muscles remained clinically unaffected during study, with stable ALSFRS-R subscores and HHD measures. However, a significant decline in mean-MUNIX and NI was detected. DISCUSSION: Mean-MUNIX and NI were more sensitive than clinical measures at detecting LMN loss in presymptomatic limbs from patients with slowly progressive ALS. Therefore, these electrophysiological biomarkers should be included in early study phases as meaningful outcome measures. Muscle Nerve 58: 204-212, 2018.
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Esclerose Lateral Amiotrófica/patologia , Neurônios Motores/patologia , Fibras Musculares Esqueléticas/patologia , Potenciais de Ação , Idoso , Biomarcadores , Contagem de Células , Progressão da Doença , Eletrodiagnóstico , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Estudos Prospectivos , Resultado do TratamentoRESUMO
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. Muscle Nerve 58: 374-380, 2018.
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Potenciais de Ação/fisiologia , Eletromiografia/normas , Neurônios Motores/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adulto , Idoso , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
INTRODUCTION: We propose a motor unit number index (MUNIX) global sum score in amyotrophic lateral sclerosis (ALS) to estimate the loss of functional motor units. METHODS: MUNIX was assessed for 18 ALS patients and 17 healthy controls in 7 muscles: the abductor pollicis brevis (APB), abductor digiti minimi (ADM), tibialis anterior (TA), deltoid, trapezius, submental complex, and orbicularis oris. RESULTS: MUNIX was significantly lower in ALS patients than in healthy controls for the APB, ADM, TA, and trapezius muscles. The MUNIX sum score of 4 muscles (ADM + APB + trapezius + TA) was lower in ALS patients (P = 0.01) and was correlated with clinical scores. DISCUSSION: The global MUNIX sum score proposed in this study estimates the loss of lower motor neurons in several body regions, including the trapezius, and is correlated with clinical impairment in ALS patients. Muscle Nerve 56: 202-206, 2017.
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Esclerose Lateral Amiotrófica/patologia , Potencial Evocado Motor/fisiologia , Neurônios Motores/fisiologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Idoso , Eletromiografia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Reproducibility is an important aspect of any method intended to be a marker of disease progression. In this study we investigated approaches for improving motor unit number index (MUNIX) reproducibility. METHODS: We used the intraclass correlation coefficient (ICC) and the coefficient of variation (CV) to study reproducibility in healthy subjects. We tested reproducibility between test and retest of a single MUNIX from 3 different muscles (S-MUNIX) and also of the mean of a set of 3 measurements from these same muscles (M-MUNIX). RESULTS: M-MUNIX was more reproducible than S-MUNIX. The CV showed a greater improvement than the ICC in all 3 muscles. CONCLUSIONS: M-MUNIX may be a valuable approach for following motor unit loss, because it is more replicable than MUNIX. This may be especially relevant in amyotrophic lateral sclerosis patients, in whom MUNIX variability is higher than in healthy individuals. Muscle Nerve, 2016 Muscle Nerve 55: 635-638, 2017.
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Potenciais de Ação/fisiologia , Neurônios Motores/fisiologia , Músculo Esquelético/fisiologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Progressão da Doença , Eletromiografia/métodos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Recrutamento Neurofisiológico/fisiologia , Reprodutibilidade dos TestesRESUMO
A successful nerve transfer surgery can provide a wealth of benefits to a patient with cervical spinal cord injury. The process of surgical decision making ideally uses all pertinent information to produce the best functional outcome. Reliance on clinical examination and imaging studies alone can miss valuable information on the state of spinal cord health. In this regard, neurophysiological evaluation has the potential to effectively gauge the neurological status of even select pools of anterior horn cells and their axons to small nerve branches in question to determine the potential efficacy of their use in a transfer. If available preoperatively, knowledge gained from such an evaluation could significantly alter the reconstructive surgical plan and avoid poor results. The authors describe their institution's approach to the assessment of patients with cervical spinal cord injury who are being considered for nerve transfer surgery in both the acute and chronic setting and broadly review the neurophysiological techniques used.
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Medula Cervical/cirurgia , Transferência de Nervo , Traumatismos da Medula Espinal/cirurgia , Extremidade Superior/cirurgia , Animais , Medula Cervical/fisiopatologia , Humanos , Transferência de Nervo/métodos , Procedimentos Neurocirúrgicos/métodos , Medula Espinal/fisiopatologia , Medula Espinal/cirurgia , Extremidade Superior/fisiopatologiaRESUMO
INTRODUCTION: Motor unit number index (MUNIX) is a quick and feasible electrophysiological technique that estimates the number of motor neurons in limb muscles in healthy and amyotrophic lateral sclerosis (ALS) subjects. In this study we explored the feasibility, reliability, and differences of MUNIX in nasalis muscles in healthy subjects and ALS patients. METHODS: MUNIX of the nasalis muscle of 50 healthy and 20 ALS subjects with bulbar involvement was compared. Functional impairment was evaluated by the ALS Functional Rating Scale-Revised and its bulbar subscore. RESULTS: MUNIX was well tolerated and quickly performed. Bulbar ALS patients showed non-significant lower nasalis MUNIX values and a lower functional bulbar subscore. Intra- and interrater reliability showed high intraclass correlation coefficients (ICCs) in healthy subjects (0.87) and ALS patients (0.92). CONCLUSION: MUNIX of the nasalis muscle is a reproducible method, but it showed no significant difference between healthy and bulbar ALS subjects and seems not to be a useful marker of disease progression in ALS. Muscle Nerve 54: 733-737, 2016.
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Potenciais de Ação/fisiologia , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Neurônios Motores/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adulto , Idoso , Eletromiografia/métodos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The split-hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS). METHODS: We compared the split-hand index (SI) calculated from the compound muscle action potential (CMAP; SICMAP ) with that calculated from the motor unit number index (MUNIX; SIMUNIX ). We performed MUNIX on the abductor policis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles of 39 ALS patients and 40 age-matched, healthy controls. SI is derived by multiplying the CMAP (or MUNIX) recorded over the APB and FDI and dividing by the CMAP (or MUNIX) recorded over the ADM. RESULTS: Receiver-operating characteristic curve analysis revealed good diagnostic accuracy for both indices, but better performance of SIMUNIX than SICMAP . CONCLUSION: SIMUNIX and SICMAP were useful in differentiating ALS patients from healthy controls. SIMUNIX appears to be a better electrophysiological marker than SICMAP for the split-hand sign of ALS. Muscle Nerve 53: 885-888, 2016.
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Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/patologia , Potencial Evocado Motor/fisiologia , Mãos/fisiopatologia , Músculo Esquelético/fisiopatologia , Idoso , Estudos de Casos e Controles , Eletromiografia , Feminino , Mãos/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Curva ROCRESUMO
INTRODUCTION: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo-facial muscles have not been reported. METHODS: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.
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Músculos Faciais/fisiologia , Neurônios Motores/fisiologia , Contração Muscular/fisiologia , Potenciais de Ação/fisiologia , Adulto , Estimulação Elétrica , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto JovemRESUMO
This study investigated the effect of handedness on motor unit number index (MUNIX). Maximal hand strength, compound muscle action potential (CMAP) and voluntary surface electromyography (EMG) signals were measured bilaterally for the first dorsal interosseous (FDI) and thenar muscles in 24 right-handed and 2 left-handed healthy subjects. Mean (±standard error) grip and pinch forces in the dominant hand were 43.99 ± 2.36 kg and 9.36 ± 0.52 kg respectively, significantly larger than those in the non-dominant hand (grip: 41.37 ± 2.29 kg, p < .001; pinch: 8.79 ± 0.46 kg, p < .01). Examination of myoelectric parameters did not show a significant difference among the CMAP area, the MUNIX or motor unit size index (MUSIX) between the two sides in the FDI and thenar muscles. In addition, there was a lack of correlation between the strength and myoelectric parameters in regression analysis. However, strong correlations were observed between dominant and non-dominant hand muscles in both strength and myoelectric measures. Our results indicate that the population of motor units or spinal motor neurons as estimated from MUNIX may not be associated with handedness. Such findings help understand and interpret the MUNIX during its application for clinical or laboratory investigations.
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Eletromiografia/métodos , Lateralidade Funcional/fisiologia , Mãos/fisiologia , Músculo Esquelético/fisiologia , Adulto , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Análise de Regressão , Processamento de Sinais Assistido por Computador , Adulto JovemRESUMO
INTRODUCTION: Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. METHODS: MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. RESULTS: The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p < .05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p < .05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p < .05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p < .05). CONCLUSION: MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.
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Paralisia de Bell , Eletromiografia , Humanos , Paralisia de Bell/fisiopatologia , Paralisia de Bell/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Eletromiografia/métodos , Músculos Faciais/fisiopatologia , Adulto Jovem , Idoso , Biomarcadores , Neurônios Motores/fisiologia , Diagnóstico Precoce , Potenciais de Ação/fisiologiaRESUMO
This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.
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Esclerose Lateral Amiotrófica , Biomarcadores , Eletromiografia , Doença dos Neurônios Motores , Neurônios Motores , Condução Nervosa , Humanos , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Neurônios Motores/fisiologia , Doença dos Neurônios Motores/fisiopatologia , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/diagnóstico , Eletromiografia/métodos , Condução Nervosa/fisiologiaRESUMO
Background: CNM-Au8® is a catalytically-active gold nanocrystal neuroprotective agent that enhances intracellular energy metabolism and reduces oxidative stress. The phase 2, randomised, double-blind, placebo-controlled trial and open label extension RESCUE-ALS trial evaluated the efficacy and safety of CNM-Au8 for treatment of amyotrophic lateral sclerosis (ALS). Methods: RESCUE-ALS and its long-term open label extension (OLE) were conducted at two multidisciplinary ALS clinics located in Sydney, Australia: (i) the Brain and Mind Centre and (ii) Westmead Hospital. The double-blind portion of RESCUE-ALS was conducted from January 16, 2020 (baseline visit, first-patient first-visit (FPFV)) through July 13, 2021 (double-blind period, last-patient last-visit (LPLV)). Participants (N = 45) were randomised 1:1 to receive 30 mg of CNM-Au8 or matching placebo daily over 36 weeks in addition to background standard of care, riluzole. The primary outcome was mean percent change in summed motor unit number index (MUNIX), a sensitive neurophysiological biomarker of lower motor neuron function. Change in total (or summated) MUNIX score and change in forced vital capacity (FVC) were secondary outcome measures. ALS disease progression events, ALS Functional Rating Scale (ALSFRS-R) change, change in quality of life (ALSSQOL-SF) were assessed as exploratory outcome measures. Long-term survival evaluated vital status of original active versus placebo randomisation for all participants through at least 12 months following last-patient last-visit (LPLV) of the double-blind period. RESCUE-ALS and the open label study are registered in clinicaltrials.gov with registration numbers NCT04098406 and NCT05299658, respectively. Findings: In the intention-to-treat (ITT) population, there was no significant difference in the summated MUNIX score percent change (LS mean difference: 7.7%, 95% CI: -11.9 to 27.3%, p = 0.43), total MUNIX score change (18.8, 95% CI: -56.4 to 94.0), or FVC change (LS mean difference: 3.6, 95% CI: -12.4 to 19.7) between the active and placebo treated groups at week 36. In contrast, survival analyses through 12-month LPLV demonstrated a 60% reduction in all-cause mortality with CNM-Au8 treatment [hazard ratio = 0.408 (95% Wald CI: 0.166 to 1.001, log-rank p = 0.0429). 36 participants entered the open label extension (OLE), and those initially randomised to CNM-Au8 exhibited a slower rate of disease progression, as measured by time to the occurrence of death, tracheostomy, initiation of non-invasive ventilatory support, or gastrostomy tube placement. CNM-Au8 was well-tolerated, and no safety signals were observed. Interpretation: CNM-Au8, in combination with riluzole, was well-tolerated in ALS with no identified safety signals. While the primary and secondary outcomes of this trial were not significant, the clinically meaningful exploratory results support further investigation of CNM-Au8 in ALS. Funding: The RESCUE-ALS was substantially funded by a grant from FightMND. Additional funding was provided by Clene Australia Pty Ltd.
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Objective: To compare the utility of MUNIX (motor unit number index) with needle EMG in characterizing motor unit (MU) properties in the biceps brachii (BB) muscle in subjects with remote polio. Methods: Thirty subjects suffering from remote polio were investigated with MUNIX and needle EMG, all with Macro EMG and 16 of these subjects with concentric needle EMG. Results: Both MUNIX and the needle EMG methods showed abnormal results. Fiber density (FD) was the most sensitive parameter for showing signs of reinnervation. At a group level, the methods showed neurogenic findings, but there was no correlation between the results of the MUNIX and needle EMG investigations. Conclusions: Both MUNIX and needle EMG are valuable methods for measuring neurogenic involvement in the BB muscle. However, there was a lack of correlation between the MUNIX and needle EMG findings. The cause for this missing correlation may be multifactorial as there are several differences between the methods. Significance: The reason for the lack of correlation between the MUNIX and needle EMG results is discussed. By combining the needle and surface recorded methods one can obtain more information on the denervation and reinnervation process compared to using just one of the methods alone.