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.

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia.

Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy.

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).

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.

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.

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.

Imbalance of cortical facilitatory and inhibitory circuits underlies hyperexcitability in ALS.

Objective: To determine the relative contribution of inhibitory and facilitatory circuits in the development of cortical hyperexcitability in amyotrophic lateral sclerosis (ALS).

Methods: In this cross-sectional study, cortical excitability was assessed in 27 patients with ALS, and results compared to 25 healthy controls. In addition, a novel neurophysiologic measure of cortical function, short-interval intracortical facilitation (SICF), was assessed reflecting activity of the facilitatory circuits.

Reproducibility of motor unit number index and multiple point stimulation motor unit number estimation in controls.

Introduction: Reproducibility of the multiple point stimulation motor unit number estimation (MPS-MUNE) technique was compared with the recently developed motor unit number index (MUNIX) technique.

Methods: MPS-MUNE and MUNIX were performed on 15 healthy subjects at 3 different time-points by the same examiner. Reproducibility was analyzed using intraclass correlation coefficient (ICC) and coefficient of variation (CV).

Primary lateral sclerosis and the amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

Aim: To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum of diseases.

Methods: Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n = 27) and ALS-FTD (n = 12). Clinical features, Addenbrooke's Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented.

Physiological Processes Underlying Short Interval Intracortical Facilitation in the Human Motor Cortex.

Short interval intracortical facilitation (SICF) may be elicited by a paired pulse transcranial magnetic stimulation (TMS) paradigm, whereby a suprathreshold first stimulus (S1) precedes a perithreshold second stimulus (S2). Other facilitatory circuits can be probed by TMS such as intracranial facilitation, however the cortical contributions to these circuits may lie partially outside of M1. SICF as such represents a unique analog to M1 inhibitory circuits such as short interveal intracortical circuits.

Cortical function and corticomotoneuronal adaptation in monomelic amyotrophy.

Objective: To evaluate corticomotoneuronal integrity in monomelic amyotrophy using threshold tracking transcranial magnetic stimulation (TT-TMS).

Methods: Cortical excitability studies were prospectively performed in 8 monomelic amyotrophy patients and compared to 21 early-onset amyotrophic lateral sclerosis (ALS) patients and 40 healthy controls. Motor evoked potentials responses were recorded over abductor pollicis brevis.

The evolution of motor cortical dysfunction in amyotrophic lateral sclerosis.

Objective: The present study aimed to investigate alterations in cortical function in amyotrophic lateral sclerosis (ALS) related to disease progression.

Methods: In total, clinical assessments were evaluated in 189 ALS patients, combined with assessment of cortical function utilising threshold tracking transcranial magnetic stimulation. Results were compared with disease stage.

Physiological processes influencing motor-evoked potential duration with voluntary contraction.

Voluntary contraction leads to facilitation of motor-evoked potentials (MEPs) producing greater amplitude, shorter onset latency, and prolonged duration of the electromyography potential. Whereas hyperexcitability of spinal motoneurons and changes in descending corticospinal volleys have been proposed as putative mechanisms for changes in MEP amplitude and onset latency, a contribution of propriospinal interneurons, exerting modulatory effects on α-motoneurons, has been proposed as a potential explanation for prolongation of MEP duration. The aim of the present study is to gain further insight into the physiological processes underlying changes in MEP duration.

Pathophysiological and diagnostic implications of cortical dysfunction in ALS.

Cortical dysfunction - specifically, the development of hyperexcitability - seems to be an early and intrinsic feature of sporadic and familial amyotrophic lateral sclerosis (ALS) phenotypes, preceding the onset of lower motor neuron dysfunction and correlating with ensuing lower motor neuron dysfunction and degeneration. In fact, cortical dysfunction could provide a pathogenic basis for ALS, with corticomotor neuronal hyperexcitability mediating motor neuron degeneration via a trans-synaptic, glutamate-mediated, excitotoxic mechanism. The recent identification of C9orf72 repeat expansion as an important genetic risk factor for both ALS and frontotemporal dementia has underscored the importance of cortical function in ALS pathogenesis, and has helped to confirm that the disease forms part of a spectrum of central neurodegenerative processes.

Diagnostic criteria in amyotrophic lateral sclerosis: A multicenter prospective study.

Objective: To assess the sensitivity and specificity of the Awaji and revised El Escorial diagnostic criteria (rEEC) in amyotrophic lateral sclerosis (ALS).

Methods: We conducted a large prospective multicenter study, recruiting 416 patients (253 male, 163 female) between January 1, 2012, and August 31, 2015, to compare the diagnostic accuracy of Awaji and rEEC in accordance with standards of reporting of diagnostic accuracy criteria.

Results: The sensitivity of the Awaji criteria (57%, 50.

Postural tremor and chronic inflammatory demyelinating polyneuropathy.

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) typically presents with a combination of sensory and motor impairments. Tremor is recognized as a common and debilitating feature in CIDP, although the underlying mechanisms are unclear.

Methods: Clinical tremor severity and disability scores were collected prospectively in 25 CIDP patients and compared with 22 neuromuscular controls.

Motor cortical function determines prognosis in sporadic ALS.

Objective: To study the relationship between cortical function and survival in amyotrophic lateral sclerosis (ALS).

Methods: A total of 216 referrals were screened, and participants with familial ALS or an inexcitable cortex were excluded. Clinical measures and phenotyping from 169 patients with sporadic ALS were combined with an assessment of cortical function using threshold tracking transcranial magnetic stimulation with indices including short interval intracortical inhibition (SICI).

Riluzole exerts transient modulating effects on cortical and axonal hyperexcitability in ALS.

Riluzole is an established therapy for amyotrophic lateral sclerosis (ALS), although its effects are modest, prolonging survival by three months on average. While the neuroprotective effects of riluzole appear to be mediated by inhibition of glutaminergic transmission and antagonization of Na channel function, the duration of these effects remains to be elucidated. Consequently, the present study combined assessment of cortical and peripheral function to determine the longitudinal effects of riluzole in ALS patients.

Awaji criteria improves the diagnostic sensitivity in amyotrophic lateral sclerosis: A systematic review using individual patient data.

Objective: To determine the utility of the Awaji criteria in diagnosing amyotrophic lateral sclerosis (ALS) and to propose a novel modification so as to enhance sensitivity based on results of individual patient data (IPD).

Methods: Individual patient data were available from 8 studies comparing the diagnostic accuracy of Awaji and revised El Escorial (rEEC) criteria. The sensitivity of a novel updated Awaji criteria, incorporating a "probable-laboratory supported" category, was also tested.