Dissecting the mechanisms underlying short-interval intracortical inhibition using exercise.

Recently, 2 physiologically distinct phases of short-interval intracortical inhibition (SICI) have been identified, a larger phase at interstimulus interval (ISI) 3 ms and a smaller phase at ISI 1 ms. While the former is mediated by synaptic processes, the mechanisms underlying the first phase of SICI remain a matter of debate. Separately, it is known that fatiguing hand exercise reduces SICI, a measure of cortical excitability.

Utilizing natural activity to dissect the pathophysiology of acute oxaliplatin-induced neuropathy.

Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na(+)/K(+) pump function.

Adaptation of motor function after spinal cord injury: novel insights into spinal shock.

The mechanisms underlying spinal shock have not been clearly defined. At present, clinical assessment remains the mainstay to describe progression through spinal shock following traumatic spinal cord injury. However, nerve excitability studies in combination with conventional nerve conduction and clinical assessments have the potential to investigate spinal shock at the level of the peripheral axon.

How common are behavioural changes in amyotrophic lateral sclerosis?

Our objectives were to assess the frequency of behavioural changes in patients with amyotrophic lateral sclerosis (ALS) and to compare the clinical profile of ALS patients with those with behavioural variant frontotemporal dementia (bvFTD). Ninety-two patients with ALS and their carers participated in a postal survey. ALS patients completed self-report measures of motor function and mood.

Corticomotoneuronal function and hyperexcitability in acquired neuromyotonia.

Acquired neuromyotonia encompasses a group of inflammatory disorders characterized by symptoms reflecting peripheral nerve hyperexcitability, which may be clinically confused in the early stages with amyotrophic lateral sclerosis. Despite a clear peripheral nerve focus, it remains unclear whether the ectopic activity in acquired neuromyotonia receives a central contribution. To clarify whether cortical hyperexcitability contributes to development of clinical features of acquired neuromyotonia, the present study investigated whether threshold tracking transcranial magnetic stimulation could detect cortical hyperexcitability in acquired neuromyotonia, and whether this technique could differentiate acquired neuromyotonia from amyotrophic lateral sclerosis.

Acute, reversible axonal energy failure during stroke-like episodes in MELAS.

The pathophysiology of stroke-like episodes in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) remains unresolved. Possible mechanisms include mitochondrial angiopathy, cytopathy, or both, collectively resulting in cellular energy depletion. To clarify disease mechanisms, axonal excitability properties were investigated in a 10-year-old child with MELAS.

Regional differences in ulnar nerve excitability may predispose to the development of entrapment neuropathy.

Objective: To assess whether there are differences in nerve excitability properties between proximal and distal stimulation sites in the ulnar nerve in healthy controls, which may provide information on whether alteration in ion channel function predisposes to the development of ulnar neuropathy at the elbow.

Methods: Nerve excitability studies were undertaken in 11 healthy controls. Studies were undertaken with stimulation of the ulnar nerve at the elbow and wrist.

Corticospinal tract dysfunction and development of amyotrophic lateral sclerosis following electrical injury.

The causal relationship between electrical injury and development of amyotrophic lateral sclerosis (ALS) remains controversial. We describe the case of a 25-year-old man who developed ALS after a severe electrical injury. Cerebral magnetic resonance imaging (MRI) demonstrated hyperintensities involving the corticospinal tract.

The 10-metre gait speed as a functional biomarker in amyotrophic lateral sclerosis.

There remains a critical need to develop biomarkers of disease progression in amyotrophic lateral sclerosis (ALS). Mobility is a key determinant of disease status and quality of life. The present study assessed the utility of 10-metre gait speed as a functional biomarker of disability in ALS.

Riluzole, neuroprotection and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease of the human motor system. Aetiological mechanisms implicated in the development of ALS have been linked to the glutamatergic neurotransmitter system, with destruction of motor neurons triggered through excessive activation of glutamate receptors at the synaptic cleft. This 'excitotoxicity' theory of ALS gave rise to the development of therapeutic approaches and ultimately clinical trials involving riluzole, initially thought to act solely as an inhibitor of glutamate release.

Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers.

Objective: Diffusion tensor imaging (DTI) recently identified structural abnormalities of corticomotoneurons in asymptomatic copper/zinc superoxide-dismutase-1 (SOD-1) gene mutation carriers. The potential existence of longstanding corticomotoneuronal dysfunction would clearly have consequences for the medical management of asymptomatic SOD-1 mutation carriers. To clarify this unexpected finding, DTI techniques were combined with threshold tracking transcranial magnetic stimulation (TMS) to assess the anatomical and functional integrity of corticomotoneurons in asymptomatic SOD-1 mutation carriers.

Changes in human sensory axonal excitability induced by focal nerve compression.

The aim of the present study was to establish the changes in nerve excitability and symptom generation associated with the application of focal nerve compression (FNC). FNC was applied at the wrist by means of a custom-designed electrode in 10 healthy subjects, and was maintained for 24 min. Symptoms of paraesthesiae and signs of numbness were recorded every 30 s.

The case of a 48 year-old woman with bizarre and complex delusions.

Background: A 48 year-old woman presented with an 18 month history of bizarre and complex delusions on a background of social, behavioral and cognitive decline over several years. Her psychosis progressed despite receiving high doses of antipsychotics. The patient's father also had a psychotic episode in his 40s.

Fatigue in multiple sclerosis: mechanisms and management.

Multiple sclerosis [MS] is a chronic immune-mediated disorder of the central nervous system [CNS]. Fatigue may be a debilitating symptom in MS patients, adversely impacting on their quality of life. Clinically, fatigue may manifest as exhaustion, lack of energy, increased somnolence, or worsening of MS symptoms.

Neurophysiological methodologies: diagnosis of peripheral nerve disease and assessment of pharmacological agents.

Recent developments in the field of neurophysiology have led to the refinement of neurophysiological techniques, enabling clinical investigators to assess neuropathy patients with greater precision. In addition to conventional nerve conduction studies and electromyography, novel axonal excitability techniques and quantitative sensory testing may be used to improve diagnosis and to characterize and serially monitor peripheral nerve disorders. A significant expansion in the number of clinical trials being conducted for neurological indications has increased the impetus to further develop neurophysiological measures that reflect the responsiveness to drug therapies.

Cortical excitability in hereditary motor neuronopathy with pyramidal signs: comparison with ALS.

Background: Distal hereditary motor neuronopathy with pyramidal features (dHMNP) is a hereditary neurodegenerative disorder characterised by the presence of upper and lower motor neuron signs. The pathophysiological mechanisms underlying these clinical findings remain elusive. Given that cortical hyperexcitability appears to underlie neurodegeneration in amyotrophic lateral sclerosis (ALS), a disorder that may clinically resemble dHMNP, the present study applied novel cortical excitability studies to further investigate the pathophysiological mechanisms in dHMNP.

Oxaliplatin-induced lhermitte's phenomenon as a manifestation of severe generalized neurotoxicity.

Objectives: Lhermitte's phenomenon, characterized by 'electric-shock' sensations precipitated by neck flexion, may develop during oxaliplatin treatment. Limited cases have been described previously and the pathophysiology underlying Lhermitte's phenomenon in oxaliplatin-treated patients has not been established.

Methods: Patients who developed Lhermitte's phenomenon during oxaliplatin therapy were investigated by neurological examination, neurotoxicity grading and conventional nerve conduction studies (NCS).

FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis.

Objective: FUS gene mutations were recently identified in familial amyotrophic lateral sclerosis (ALS). The present studies sought to define the clinical, post-mortem and neurophysiological phenotypes in ALS families with FUS mutations and to determine the frequency of FUS mutations in familial and sporadic ALS.

Methods: FUS was screened for mutations in familial and sporadic ALS cases.

INSPIRATIonAL--INSPIRAtory muscle training in amyotrophic lateral sclerosis.

Respiratory impairment, due to respiratory muscle weakness, is a major cause of morbidity and mortality in patients with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Threshold loading may strengthen the inspiratory muscles and thereby improve patient prognosis. A phase II, double-blind, randomized-controlled trial was undertaken to determine whether a 12-week inspiratory muscle training programme attenuated the decline in respiratory function and inspiratory muscle strength in patients with ALS/MND.

Ischaemic sensitivity of axons in carpal tunnel syndrome.

Although carpal tunnel syndrome (CTS) is the most common human entrapment neuropathy characterized by paraesthesiae and numbness with nocturnal exacerbation, the mechanisms underlying the generation of these symptoms remain unclear. Consequently, the aim of the present study was to investigate the relationship between changes in axonal excitability and the development of neurological symptoms in response to an ischaemic insult in CTS patients. Sensory and motor excitability were measured in 10 CTS patients and compared with 10 healthy controls, with participants asked to report symptom generation and intensity during the development of limb ischaemia.

Spinal muscular atrophy: molecular mechanisms.

Spinal muscular atrophy (SMA) is a relatively common autosomal recessive neuromuscular disorder characterised by muscle weakness and atrophy due to degeneration of motor neurons of the spinal cord and cranial motor nuclei. The clinical phenotype incorporates a wide spectrum. No effective treatment is currently available and patients may experience severe physical disability which is often life limiting.

Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy.

Administration of oxaliplatin, a platinum-based chemotherapy used extensively in the treatment of colorectal cancer, is complicated by prominent dose-limiting neurotoxicity. Acute neurotoxicity develops following oxaliplatin infusion and resolves within days, while chronic neuropathy develops progressively with higher cumulative doses. To investigate the pathophysiology of oxaliplatin-induced neurotoxicity and neuropathy, clinical grading scales, nerve conduction studies and a total of 905 axonal excitability studies were undertaken in a cohort of 58 consecutive oxaliplatin-treated patients.