Prolonged compound muscle action potential duration in critical illness myopathy

Critical illness myopathy (CIM) is a frequent cause of generalized weakness in the intensive care unit. Prolonged compound muscle action potential (CMAP) durations have been described in this patient population, and this study presents further data on CMAP duration in normal controls and patients with CIM. The findings highlight the importance of testing multiple nerve muscle combinations in weak, critically ill patients. Recognition of this pattern, which has not been widely described, can facilitate the diagnosis of CIM. Muscle Nerve, 2009     

Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle

Abstract. The pathogenesis of myopathies occurring in critically ill patients (critical illness myopathy, CIM) is poorly understood. Both local and systemic responses to sepsis and other severe insults to the body are presumed to be involved but the precise mechanisms by which muscle function is impaired are far from clear. To elucidate such mechanisms we investigated the effects of blood serum fractions (5 kDa to 100 kDa molecular weight cut-off, MWCO) from patients with CIM and from control persons on membrane and contractile functions in intact mammalian single skeletal muscle fibres and chemically skinned fibre bundles. In intact fibres, resting membrane potentials were less negative when exposed to CIM serum fractions compared with control serum fractions. Half-width and maximum rise time of action potentials (AP) were smaller in CIM serum low MWCO fractions vs. control serum. Peak amplitudes of fast inward sodium currents (I_Na) were increased by low MWCO-CIM fractions compared with control sera fractions. Additionally, voltage dependent inactivation of I_Na was shifted towards more positive potentials by high MWCO fractions of CIM sera. In skinned fibres, pCa-force relations were similar in CIM and control serum fractions but peak force of Ca²⁺ induced force transients was decreased by low MWCO-CIM vs. control serum fractions. Our results (i) provide the first evidence that serum from CIM patients affects membrane excitability and the excitation-contraction coupling process at the level of the sarcoplasmic reticulum Ca²⁺ release of mammalian muscle fibres and (ii) also show that even control serum fractions per se alter the response to important physiological membrane and contractility parameters compared with physiological saline.     

Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness MYOPATHIES

Introduction: In severe acute quadriplegic myopathy in intensive care unit (ICU) patients, muscle fibers are electrically inexcitable; in critical illness polyneuropathy, the excitability remains normal. Conventional electrodiagnostic methods do not provide the means to adequately differentiate between them. In this study we aimed to further optimize the methodology for the study of critically ill ICU patients and to create a reference database in healthy controls. Methods: Different electrophysiologic protocols were tested to find sufficiently robust and reproducible techniques for clinical diagnostic applications. Results: Many parameters show large test–retest variability within the same healthy subject. Reference values have been collected and described as a basis for studies of weakness in critical illness. Conclusions: Using the ratio of neCMAP/dmCMAP (response from nerve and direct muscle stimulation), refractory period, and stimulus–response curves may optimize the electrodiagnostic differentiation of patients with critical illness myopathy from those with critical illness polyneuropathy. Muscle Nerve 53 : 555–563, 2016     

Reversible electrophysiological abnormalities in hypokalemic paralysis: Case report of two cases

Compound muscle action potential (CMAP) amplitude declines during a paralytic attack in patients with hypokalemic periodic paralysis (HPP). However, serial motor nerve conduction studies in hypokalemic paralysis have not been commonly reported. We report two cases with hypokalemic paralysis, who had severely reduced CMAPs in all motor nerves at presentation during the episode of quadriparesis. However, the amplitude of CMAPs increased and reached normal levels, as the serum potassium concentration and motor power returned to normal state.     

Muscle fiber conduction velocity in the diagnosis of familial hypokalemic periodic paralysis—invasive versus surface determination

Muscle fiber conduction velocity (MFCV) in the brachial biceps muscle was determined in a large family of patients with hypokalemic periodic paralysis (HOPP) by both a surface and an invasive method. Other surface EMG parameters and the muscle force were also determined. Both the surface and the invasive method showed a significantly lower mean MFCV in the proven gene carriers but only the invasive method showed a lower MFCV in all proven carriers. It can be concluded that MFCV determination is a reliable method to detect the membrane defect in HOPP carriers and that the invasive method is not only easy to perform, but also more sensitive. The muscle force and the integrated EMG at maximal voluntary contraction were lower in the carrier group. A positive correlation between the surface MFCV and the neuromuscular efficiency (the quotient of force and integrated EMG) was found in the controls but not in the HOPP carriers. Since type II fibers have a higher neuromuscular efficiency, this suggests a preferential involvement of type II fibers in HOPP. © 1994 John Wiley & Sons, Inc.     

Effect of muscle-fiber velocity recovery function on motor unit action potential properties in voluntary contractions

Measurements of muscle-fiber conduction velocity during voluntary contractions have been used in the diagnosis of neuromuscular diseases. However, the velocity of propagation of action potentials depends on the interspike interval of activation due to the velocity recovery function (VRF) of muscle fibers. The comparison of muscle-fiber conduction velocity estimates between individuals may thus be influenced by differences in motor unit discharge rate. This study investigates action potential properties of motor units of the sternocleidomastoid muscle during voluntary modulation of discharge rate with the purpose of assessing the effect of the VRF on motor unit properties in voluntary contractions. Nineteen healthy men trained to control a target motor unit with feedback of surface multichannel electromyographic (EMG) signals. The subjects performed three 30-s contractions of cervical flexion/rotation modulating the discharge rate of the target motor unit from 6.6 +/- 1.6 pps to 28.0 +/- 6.4 pps. Action potential conduction velocity was correlated to instantaneous discharge rate (R = 0.38 +/- 0.21). Action potential conduction velocity, peak-to-peak amplitude, and duration varied between minimum and maximum discharge rate (P < 0.01; percent change 12.3 +/- 5.0, -11.8 +/- 9.9, and -12.9 +/- 7.3). Thus, the properties of surface motor unit action potentials vary with modulation of discharge rate. This has implications for the use of conduction velocity values measured during voluntary contractions to differentiate patient populations from healthy individuals and for the development of normative data.     

Muscle-fiber conduction velocity and electromyography as diagnostic tools in patients with suspected inflammatory myopathy: a prospective study

Combinations of different techniques can increase the diagnostic yield from neurophysiological examination of muscle. In 25 patients with suspected inflammatory myopathy, we prospectively performed needle electromyography (EMG) and measured muscle-fiber conduction velocity (MFCV) in a single muscle, using a technique with direct muscle-fiber stimulation and recording. Results of MFCV were compared with final diagnosis, EMG, and needle muscle biopsy. Diagnostic accuracy of combined MFCV and EMG studies was 72%, compared to 60% for EMG alone. This improvement was due to a gain in specificity. The MFCV did not prove useful in discriminating inflammatory myopathy from other myopathies. Furthermore, we found a correlation of 92% between variability of MFCV and myopathic changes in muscle biopsy. We conclude that the utility of electrodiagnostic examination can be increased if EMG examination is combined with MFCV studies.     

Estimation of voluntary elicited motor neuron discharge using a peripheral nerve collision technique at different contraction strengths

Objective

To estimate non-invasively the amount, recruitment pattern and discharge frequency of spinal motor neurons (MN) at contraction strength >20% of maximal voluntary contraction (MVC) of small hand muscles.

Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases

Current electrophysiologic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are highly specific but poorly sensitive. The required extensiveness and best practical way of performing nerve conduction studies to achieve optimal sensitivity remain unknown. We here initially retrospectively analyzed the motor nerve conduction study results of 20 consecutive patients with a clinical diagnosis of CIDP (four performed prior to, and 16 after, treatment initiation) to assess the sensitivity of six published sets of criteria (Nicolas et al., 2002; Thaisetthawatkul et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Magda et al., 2003; Hughes et al., 2001; Saperstein et al., 2001), as well as four combinations (Nicolas et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Hughes et al., 2001; Saperstein et al., 2001, each individually combined with Thaisetthawatkul et al., 2002). Sensitivity was highest for the combination of Nicolas et al. (2002) and Thaisetthawatkul et al. (2002) (100%). We then determined the sensitivity of this combined criteria, using five different, hypothetical, nerve conduction study protocols, applied retrospectively to the neurophysiologic data of our 20 patients (exclusive upper limb studies with proximal stimulations; exclusive lower limb studies; full forearm and foreleg studies without proximal stimulations; right-sided studies with proximal stimulations; and left-sided studies with proximal stimulations). The findings showed that exhaustive upper limb or, alternatively, four-limb forearm and foreleg testing would have proved considerably more sensitive than unilateral or lower limb studies to achieve an electrophysiologic diagnosis of CIDP.     

The electrophysiology of axonal neuropathies: More than just evidence of axonal loss

It is common belief that axonal neuropathies are characterized by simple axonal degeneration and loss and that the electrophysiological correlates are just reduced compound muscle action potential and sensory nerve action potential amplitudes with normal or slightly slow conduction velocity. However, axonal autoimmune neuropathies with involvement of the nodal region and axonal neuropathies due to energy restriction such as occurring in nerve ischemia, thiamine deficiency, critical illness, and mitochondrial disorders present conduction failure that can be either reversible with prompt recovery or progress to axonal degeneration with poor outcome. Moreover autoimmune axonal neuropathies due to nodal voltage gated sodium channels dysfunction/disruption may show slowing of conduction velocity, even in the demyelinating range, possibly due to prolongation of the depolarization time required to reach the threshold for action potential regeneration at subsequent nodes. These observations widen the spectrum of the electrophysiological features in some axonal neuropathies, should be taken into account to avoid misdiagnoses and for correct prognostication, and should stimulate the quest of timely targeted treatments that can eventually halt the progression from conduction failure to axonal degeneration.     

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.     

The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review

ObjectiveAmyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS.MethodsWe searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients.ResultsA wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials.ConclusionSurface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians.SignificanceSurface EMG techniques can enrich effective biomarker development in ALS.     

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

ObjectiveHypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca_v1.1, and Na_v1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Na_v1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo.MethodsMVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26).ResultsMuscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges.ConclusionsThe in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita.SignificanceMVRCs provide important in vivo data that complements expression studies of ion channel mutations.