Muscle ultrasound aids diagnosis in amyotrophic lateral sclerosis.

Objective: There is a need for improved diagnostic tools in Amyotrophic Lateral Sclerosis (ALS). Our objective was to assess muscle ultrasound as a diagnostic tool in patients with ALS and determine a simplified screening protocol to aid implementation in clinical practice.

Methods: Ultrasound of bulbar and limb muscles was prospectively performed on all patients referred to a single centre with suspected ALS.

Physiological Biomarkers of Upper Motor Neuron Dysfunction in ALS.

Upper motor neuron (UMN) dysfunction is an important feature of amyotrophic lateral sclerosis (ALS) for the diagnosis and understanding of pathogenesis. The identification of UMN signs forms the basis of ALS diagnosis, although may be difficult to discern, especially in the setting of severe muscle weakness. Transcranial magnetic stimulation (TMS) techniques have yielded objective physiological biomarkers of UMN dysfunction in ALS, enabling the interrogation of cortical and subcortical neuronal networks with diagnostic, pathophysiological, and prognostic implications.

Cortical inexcitability in ALS: correlating a clinical phenotype.

Background: Cortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic and clinical characteristics were contrasted with normal or hyperexcitable ALS cohorts to assess the impact of cortical inexcitability on ALS phenotype and survival.

Methods: Threshold-tracking transcranial magnetic stimulation (TMS) technique with measurement of mean short interval intracortical inhibition (SICI) differentiated ALS patients into three groups (1) inexcitable (no TMS response at maximal stimulator output in the setting of preserved lower motor neuron (LMN) function), (2) hyperexcitable (SICI≤5.5%) and (3) normal cortical excitability (SICI>5.

Novel approaches to assessing upper motor neuron dysfunction in motor neuron disease/amyotrophic lateral sclerosis: IFCN handbook chapter.

Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function.

Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.

Background And Purpose: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated.

Utility of split hand index with different motor unit number estimation techniques in ALS.

Objective: Utility of the split hand index (SI) in amyotrophic lateral sclerosis (ALS) has been reported when using the compound muscle action potential (CMAP) amplitude method (SI). A motor unit number index (MUNIX) based SI method (SI) was purported to exhibit higher sensitivity. The present study assessed the clinical utility of SI, derived by CMAP amplitude, MUNIX and MScan-MUNE (SI) methods, in ALS.

Dependence of cortical neuronal strength-duration properties on TMS pulse shape.

Objective: The aim of present study was to explore the effects of different combinations of transcranial magnetic stimulation (TMS) pulse width and pulse shape on cortical strength-duration time constant (SDTC) and rheobase measurements.

Methods: Resting motor thresholds (RMT) at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M-ratios of 0.2, 0.

Cortical inhibition and facilitation are mediated by distinct physiological processes.

A complex interaction of inhibitory and facilitatory interneuronal processes may underlie development of cortical excitability in the human motor cortex. To determine whether distinct interneuronal processes mediated cortical excitability, threshold tracking transcranial magnetic stimulation was utilised to assess cortical excitability, with figure-of-eight coil oriented in posterior-anterior (PA), anterior-posterior (AP) and latero-medial (LM) directions. Motor evoked potential (MEP) responses were recorded over the contralateral abductor pollicis brevis.

Cortical hyperexcitability and plasticity in Alzheimer's disease: developments in understanding and management.

Introduction: Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that provides important insights into Alzheimer's Disease (AD). A significant body of work utilizing TMS techniques has explored the pathophysiological relevance of cortical hyperexcitability and plasticity in AD and their modulation in novel therapies.

Areas Covered: This review examines the technique of TMS, the use of TMS to examine specific features of cortical excitability and the use of TMS techniques to modulate cortical function.

The split-elbow index: A biomarker of the split elbow sign in ALS.

Objective: The split elbow sign is a clinical feature of amyotrophic lateral sclerosis (ALS), characterised by preferential weakness of biceps brachii muscle compared to triceps. A novel neurophysiological index, termed the , was developed to quantify the split-elbow sign, and assess its utility in ALS.

Methods: Clinical and neurophysiological assessment was prospectively undertaken on 34 ALS patients and 32 ALS mimics.

Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes.

Split-hand index: A diagnostic and prognostic marker in amyotrophic lateral sclerosis across varying regions of onset.

Objective: The split-hand index (SI), a reliable diagnostic marker of amyotrophic lateral sclerosis (ALS), was prospectively assessed for differences across ALS subtypes and between the onset side of clinical symptoms or the dominant and contralateral sides. In addition, the prognostic utility of the SI was longitudinally assessed.

Methods: Two hundred and forty-five ALS patients underwent measurement of SI on both sides compared with 126 neuromuscular mimic disorders (NMD).

Association of Cortical Hyperexcitability and Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis.

Objective: To determine whether cortical hyperexcitability was more prominent in cognitively impaired patients with amyotrophic lateral sclerosis (ALS).

Methods: Threshold tracking transcranial magnetic stimulation (TMS) was used to assess cortical excitability and cognitive function was determined by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Cognitive impairment was defined by ECAS < 105.

Pathophysiological associations of transcallosal dysfunction in ALS.

Aim: Involvement of the corpus callosum has been identified as a feature of amyotrophic lateral sclerosis (ALS), particularly through neuropathological studies. The aim of the present study was to determine whether alteration in transcallosal function contributed to the development of ALS, disease progression and thereby functional disability.

Methods: Transcallosal function and motor cortex excitability were assessed in 17 ALS patients with results compared to healthy controls.

TDP-43 proteinopathies: a new wave of neurodegenerative diseases.

Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclusions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding () and unrelated genes (eg, ).

Cortical hyperexcitability evolves with disease progression in ALS.

Objective: Cortical hyperexcitability has been established as an early feature of amyotrophic lateral sclerosis (ALS). The evolution of cortical hyperexcitability with ALS progression remains to be fully elucidated. This study aims to investigate changes in cortical function in ALS with disease progression.

Interneuronal networks mediate cortical inhibition and facilitation.

Objective: Recruitment of interneuronal circuits generating later indirect (I) waves seem to be important in short-interval intracortical inhibition (SICI) and facilitation (SICF) development. This study assessed whether individual variations in intracortical inhibition and facilitation could be explained by variation in recruitment of interneuronal networks.

Methods: Cortical excitability was assessed using a figure of eight coil, with motor evoked responses recorded over the contralateral abductor pollicis brevis (APB) muscle.

Reproducibility of motor unit number index and MScanFit motor unit number estimation across intrinsic hand muscles.

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.

Motor neuron disease with malignancy: Clinical and pathophysiological insights.

Objective: While some regard an association between motor neuron disease (MND) and malignancy as co-incidental, others have argued that it could represent a distinct clinical entity. The present study undertook in depth phenotyping along with assessment of cortical function to further explore disease pathophysiology in MND with malignancy (MND-M) patients.

Methods: Clinical features along with assessment of peripheral and cortical function was undertaken in 13 MND-M and results were compared to sporadic and familial MND cohorts.

Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder of the motor neurons, characterized by focal onset of muscle weakness and incessant disease progression. While the presence of concomitant upper and lower motor neuron signs has been recognized as a pathognomonic feature of ALS, the pathogenic importance of upper motor neuron dysfunction has only been recently described. Specifically, transcranial magnetic stimulation (TMS) techniques have established cortical hyperexcitability as an important pathogenic mechanism in ALS, correlating with neurodegeneration and disease spread.

Amyotrophic lateral sclerosis diagnostic index: Toward a personalized diagnosis of ALS.

Objective: The aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).

Methods: A prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment.

Utility of threshold tracking transcranial magnetic stimulation in ALS.

Upper motor neuron [UMN] and lower motor neuron [LMN] dysfunction, in the absence of sensory features, is a pathognomonic feature of amyotrophic lateral sclerosis [ALS]. Although the precise mechanisms have yet to be elucidated, one leading hypothesis is that UMN precede LMN dysfunction, which is induced by anterograde glutamatergic excitotoxicity. Transcranial magnetic stimulation (TMS) is a neurophysiological tool that provides a non-invasive and painless assessment of cortical function.