Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome.

Background: The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM.

Ageing contributes to phenotype transition in a mouse model of periodic paralysis.

Background: Periodic paralysis (PP) is a rare genetic disorder in which ion channel mutation causes episodic paralysis in association with hyper- or hypokalaemia. An unexplained but consistent feature of PP is that a phenotype transition occurs around the age of 40, in which the severity of potassium-induced muscle weakness declines but onset of fixed, progressive weakness is reported. This phenotype transition coincides with the age at which muscle mass and optimal motor function start to decline in healthy individuals.

The long exercise test as a functional marker of periodic paralysis.

Aims: The aim of this study was to evaluate the sensitivity of the long exercise test (LET) in the diagnosis of periodic paralysis (PP) and assess correlations with clinical phenotypes and genotypes.

Methods: From an unselected cohort of 335 patients who had an LET we analyzed 67 patients with genetic confirmation of PP and/or a positive LET.

Results: 32/45 patients with genetically confirmed PP had a significant decrement after exercise (sensitivity of 71%).

The role of potassium in muscle membrane dysfunction in end-stage renal disease.

Objective: Uremic myopathy is a condition seen in end-stage renal disease (ESRD), characterized by muscle weakness and muscle fatigue, in which the pathophysiology is uncertain. The aim of this study was to assess the role of abnormal serum constituents in ESRD patients by relating them to the excitability properties of the tibialis anterior muscle, at rest and during electrically induced muscle activation, by recording muscle velocity recovery cycles (MVRC) and frequency ramp responses.

Methods: Eighteen ESRD patients undergoing hemodialysis were evaluated by blood sample, MVRC, and frequency ramp (before and near the end of dialysis treatment), quantitative electromyography, and nerve conduction studies.

Alpha coma EEG pattern in patients with severe COVID-19 related encephalopathy.

Objective: Encephalopathy is a major neurological complication of severe Coronavirus Disease 2019 (COVID-19), but has not been fully defined yet. Further, it remains unclear whether neurological manifestations are primarily due to neurotropism of the virus, or indirect effects, like cerebral hypoxia.

Methods: We analysed the electroencephalograms (EEGs) of 19 consecutive patients with laboratory-confirmed COVID-19, performed at peak disease severity as part of their clinical management.

Muscle Velocity Recovery Cycles to Examine Muscle Membrane Properties.

Although conventional nerve conduction studies (NCS) and electromyography (EMG) are suitable for the diagnosis of neuromuscular disorders, they provide limited information about muscle fiber membrane properties and underlying disease mechanisms. Muscle velocity recovery cycles (MVRCs) illustrate how the velocity of a muscle action potential depends on the time after a preceding action potential. MVRCs are closely related to changes in membrane potential that follow an action potential, thereby providing information about muscle fiber membrane properties.

In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis.

Objective: Hypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca1.1, and Na1.4 which result in an aberrant gating pore current.

Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation.

The sarcolemmal voltage gated sodium channel Na1.4 conducts the key depolarizing current that drives the upstroke of the skeletal muscle action potential. It contains four voltage-sensing domains (VSDs) that regulate the opening of the pore domain and ensuing permeation of sodium ions.

In vivo assessment of muscle membrane properties in the sodium channel myotonias.

Introduction: The gain-of-function mutations that underlie sodium channel myotonia (SCM) and paramyotonia congenital (PMC) produce differing clinical phenotypes. We used muscle velocity recovery cycles (MVRCs) to investigate membrane properties.

Methods: MVRCs and responses to trains of stimuli were compared in patients with SCM (n = 9), PMC (n = 8), and normal controls (n = 26).

Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia.

Objective: To explore potential spreading to peripheral nerves of the mitochondrial dysfunction in chronic progressive external ophthalmoplegia (CPEO) by assessing axonal excitability.

Methods: CPEO patients (n=13) with large size deletion of mitochondrial DNA and matching healthy controls (n=22) were included in a case-control study. Muscle strength was quantified using MRC sum-score and used to define two groups of patients: CPEO-weak and CPEO-normal (normal strength).

Medullary infarction causing coexistent SUNCT and trigeminal neuralgia.

Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or with autonomic symptoms (SUNA) are grouped together within the trigeminal autonomic cephalalgias (TACs). However, the SUNCT and SUNA phenotype and management overlap with those of trigeminal neuralgia (TN). Additionally, a broad variety of cerebral pathologies are reportedly able to trigger either TN- or SUNCT-like pain, and emerging structural neuroimaging findings suggest the possible role of neurovascular conflict with the trigeminal nerve in SUNCT, further supporting aetiological and pathophysiological overlaps among SUNCT, SUNA and TN.

In vivo assessment of muscle membrane properties in myotonic dystrophy.

Introduction: Myotonia in myotonic dystrophy types 1 (DM1) and 2 (DM2) is generally attributed to reduced chloride-channel conductance. We used muscle velocity recovery cycles (MVRCs) to investigate muscle membrane properties in DM1 and DM2, using comparisons with myotonia congenita (MC).

Methods: MVRCs and responses to repetitive stimulation were compared between patients with DM1 (n = 18), DM2 (n = 5), MC (n = 18), and normal controls (n = 20).

Mutations in SCN4A: a rare but treatable cause of recurrent life-threatening laryngospasm.

Laryngospasm is a rare but potentially life-threatening occurrence in infants and usually has infective, allergic, metabolic, or anatomic causes. Underlying genetic conditions are rarely considered. Mutations in SCN4A encoding the voltage-gated sodium channel NaV1.

Chloride channels in myotonia congenita assessed by velocity recovery cycles.

Introduction: Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected.

Methods: MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls.

Episodic ataxia type 1 without episodic ataxia: the diagnostic utility of nerve excitability studies in individuals with KCNA1 mutations.

Episodic ataxia type 1 (EA1) is caused by mutations in the KCNA1 gene encoding the fast potassium channel Kv1.1 and is characterized clinically by brief episodes of ataxia and continuous and spontaneous motor unit activity. Atypical presentations, in which the predominant manifestation is related to the peripheral nervous system, may lead to the diagnosis being missed or delayed, with the potential risk of individuals receiving inappropriate or unnecessary investigations and treatment.

Membrane dysfunction in Andersen-Tawil syndrome assessed by velocity recovery cycles.

Introduction: Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs).

Muscle velocity recovery cycles: effects of repetitive stimulation on two muscles.

Introduction: We sought to characterize the excitability properties of tibialis anterior (TA) and brachioradialis (BR) muscles at rest and during electrically induced muscle activation in normal subjects.

Methods: Two centers recruited 10 subjects each. Multi-fiber velocity recovery cycles (VRCs) were recorded from TA (both centers) and BR (one center).

Validity of multi-fiber muscle velocity recovery cycles recorded at a single site using submaximal stimuli.

Objective: To examine the validity of multi-fiber muscle velocity recovery cycles (VRCs) recorded by direct muscle stimulation with submaximal stimuli.

Methods: VRCs were recorded from tibialis anterior muscle in normal volunteers with 1, 2 and 5 conditioning stimuli. Recordings were made with 6 different amplitudes of conditioning stimuli.

Hand-held nerve conduction device in carpal tunnel syndrome: a prospective study.

Introduction: We assessed the clinical impact of replacing standard neurophysiologic testing with a hand-held device (Mediracer) for diagnosis of carpal tunnel syndrome (CTS).

Methods: One hundred patients (200 hands) with suspected CTS were studied by blinded assessors [Hand-therapist (HT)1 and Consultant Neurophysiologist] using the Mediracer, followed by standard neurophysiologic testing. To simulate testing by personnel without neurological training, Mediracer recordings were analyzed separately by an assessor who had not seen the patients (HT2).

Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies.

Objective: To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological exercise test parameters.

Methods: We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.

Results: Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests.

Infantile onset myofibrillar myopathy due to recessive CRYAB mutations.

Mutations in the αB-crystallin (CRYAB) gene, encoding a small heat shock protein with chaperone function, are a rare cause of myofibrillar myopathy with autosomal-dominant inheritance, late-onset and moderate severity. We report a female infant presenting from 4 months with profound muscle stiffness, persistent creatine kinase elevation and electromyography characterized by spontaneous electrical activity and pseudomyotonic discharges. Muscle biopsy suggested a myofibrillar myopathy and genetic testing revealed homozygosity for the CRYAB mutation c.

Clinical neurophysiology of the episodic ataxias: insights into ion channel dysfunction in vivo.

Clinical neurophysiology has become an invaluable tool in the diagnosis of muscle channelopathies, but the situation is less clear cut with neuronal channelopathies. The genetic episodic ataxias are a group of disorders with heterogeneous phenotype and genotype, but share in common the feature of intermittent cerebellar dysfunction. Episodic ataxia (EA) types 1 and 2 are the most widely recognised of the autosomal dominant episodic ataxias and are caused by dysfunction of neuronal voltage-gated ion channels.