Muscle excitability testing.

Conventional electrophysiological methods, i.e. nerve conduction studies and electromyography are suitable methods for the diagnosis of neuromuscular disorders, however, they provide limited information about muscle fibre membrane properties and underlying disease mechanisms. Muscle excitability testing is a technique that provides in vivo information about muscle fibre membrane properties such as membrane potential and ion channel function. Since the 1960s, various methodologies have been suggested to examine muscle membrane properties but technical difficulties have limited its use. In 2009, an automated, fast and simple application, the so-called multi-fibre muscle velocity recovery cycles (MVRC) has accelerated the use of muscle excitability testing. Later, frequency ramp and repetitive stimulation protocols have been developed. Though this method has been used mainly in research for revealing disease mechanisms across a broad range of neuromuscular disorders, it may have additional diagnostic uses; value has been shown particularly in muscle channelopathies. This review will provide a description of the state-of-the art of methodological and clinical studies for muscle excitability testing.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Muscle velocity recovery cycles in myopathy.

OBJECTIVE: To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies. METHODS: 42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle. RESULTS: There were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy. CONCLUSIONS: The MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation. SIGNIFICANCE: MVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane.

Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Sensory and motor axonal excitability testing in early diabetic neuropathy.

OBJECTIVE: The aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing. METHODS: One hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ±â€¯0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). RESULTS: Motor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores. CONCLUSIONS: Changes in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. SIGNIFICANCE: Less pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.

Early detection of evolving critical illness myopathy with muscle velocity recovery cycles.

OBJECTIVE: To investigate the sensitivity of muscle velocity recovery cycles (MVRCs) for detecting altered membrane properties in critically ill patients, and to compare this to conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG). METHODS: Twenty-four patients with intensive care unit acquired weakness (ICUAW) and 34 healthy subjects were prospectively recruited. In addition to NCS (median, ulnar, peroneal, tibial and sural nerves) and qEMG (biceps brachii, vastus medialis and anterior tibial muscles), MVRCs with frequency ramp were recorded from anterior tibial muscle. RESULTS: MVRC and frequency ramp parameters showed abnormal muscle fiber membrane properties with up to 100% sensitivity and specificity. qEMG showed myopathy in 15 patients (63%) while polyneuropathy was seen in 3 (13%). Decreased compound muscle action potential (CMAP) amplitude (up to 58%) and absent F-waves (up to 75%) were frequent, but long duration CMAPs were only seen in one patient with severe myopathy. CONCLUSIONS: Altered muscle fiber membrane properties can be detected in patients with ICUAW not yet fulfilling diagnostic criteria for critical illness myopathy (CIM). MVRCs may therefore serve as a tool for early detection of evolving CIM. SIGNIFICANCE: CIM is often under-recognized by intensivists, and large-scale longitudinal studies are needed to determine its incidence and pathogenesis.

Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

MScanFit motor unit number estimation and muscle velocity recovery cycle recordings in diabetic polyneuropathy.

OBJECTIVE: Motor Unit Number Estimation (MUNE) methods may be valuable in tracking motor unit loss in diabetic polyneuropathy (DPN). Muscle Velocity Recovery Cycles (MVRCs) provide information about muscle membrane properties. This study aimed to examine the utility of the MScanFit MUNE in detecting motor unit loss and to test whether the MVRCs could improve understanding of DPN pathophysiology. METHODS: Seventy-nine type-2 diabetic patients were compared to 32 control subjects. All participants were examined with MScanFit MUNE and MVRCs in anterior tibial muscle. Lower limb nerve conduction studies (NCS) in peroneal, tibial and sural nerves were applied to diagnose large fiber neuropathy. RESULTS: NCS confirmed DPN for 47 patients (DPN + ), with 32 not showing DPN (DPN-). MScanFit showed significantly decreased MUNE values and increased motor unit sizes, when comparing DPN + patients with controls (MUNE = 71.3 ± 4.7 vs 122.7 ± 3.8), and also when comparing DPN- patients (MUNE = 103.2 ± 5.1) with controls. MVRCs did not differ between groups. CONCLUSIONS: MScanFit is more sensitive in showing motor unit loss than NCS in type-2 diabetic patients, whereas MVRCs do not provide additional information. SIGNIFICANCE: The MScanFit results suggest that motor changes are seen as early as sensory, and the role of axonal membrane properties in DPN pathophysiology should be revisited.

Detecting peripheral motor nervous system involvement in chronic spinal cord injury using two novel methods: MScanFit MUNE and muscle velocity recovery cycles.

OBJECTIVE: To examine the peripheral nervous system (PNS) in spinal cord injured (SCI) patients using two novel methods: (1) MScanFit MUNE; a motor unit number estimation method detecting motor unit loss and (2) muscle velocity recovery cycles (MVRCs) measuring muscle membrane properties which has previously shown depolarization of the muscle membrane in denervated muscles. METHODS: Thirty chronic SCI patients (lesion above Th10) and twenty-five gender -and age matched healthy controls (HC) were examined. MScanFit was recorded from peroneal nerve to anterior tibial muscle (TA) and tibial nerve to abductor hallucis muscle after excluding localized mononeuropathies. MVRCs were recorded from TA. RESULTS: Nerve conduction studies showed mononeuropathy in 8 patients (27%) (sciatic (2), -or peroneal nerve (6)). SCI patients had in average reduced motor unit number compared with HC and prolonged muscle refractory period and reduced supernormality. SIGNIFICANCE: A high prevalence of nerve lesion and a diffuse affection of the PNS following SCI are highly relevant findings that should be accounted for when planning neurorehabilitation for persons living with SCI.

Diffusion tensor imaging MR Neurography detects polyneuropathy in type 2 diabetes.

AIM: To evaluate if diffusion-tensor-imaging MR-Neurography (DTI-MRN) can detect lesions of peripheral nerves due to polyneuropathy in patients with type 2 diabetes. METHODS: Ten patients with type 2 diabetes with polyneuropathy (DPN), 10 patients with type 2 diabetes without polyneuropathy (nDPN) as well as 20 healthy controls (HC) were included. DTI-MRN covered proximal (sciatic nerve) and distal regions (tibial nerve) of the lower extremity. Fractional-anisotropy (FA) and diffusivity (mean (MD), axial (AD) and radial (RD)) were calculated and compared to neuropathy severity. Conventional T2-relaxation-time and proton-spin-density data were obtained from a multi-echo SE sequence. Furthermore, we evaluated sensitivity and specificity of DTI-MRN from receiver operating characteristics (ROC). RESULTS: The proximal and distal FA was lowest in patients with DPN compared with nDPN and HC (p < 0.01). Likewise, proximal and distal RD was highest in patients with DPN (p < 0.01). MD and AD were also significantly different though less pronounced. ROC curve analyses of DTI separated nDPN and DPN with area-under-the-curve values ranging from 0.65 to 0.98. T2-relaxation-time and proton-spin-density could not differentiate between nDPN and DPN. CONCLUSION: DTI-MRN accurately detects DPN by lower nerve FA and higher RD. These alterations are likely to reflect both proximal and distal nerve fiber pathology in patients with type 2 diabetes.

Evidence-based recommendations for examination and diagnostic strategies of polyneuropathy electrodiagnosis.

The purpose of this report is to recommend evidence-based strategies for polyneuropathy (PNP) electrodiagnosis based on a large cohort of patients examined prospectively. Nerve conduction studies (NCS) of bilateral tibial, peroneal and sural nerves, the latter with both near-nerve-technique (NNT) and surface recordings, were done in 313 patients with clinically suspected PNP. Bilateral dorsal sural and medial plantar nerves, and unilateral median and ulnar nerves were further examined in a subgroup of patients. The final clinical diagnosis retrieved from the patients medical records 1-6 years after the neurophysiological investigation served as diagnostic reference standard. The clinical follow-up diagnosis confirmed PNP in 219 patients. The tibial nerve was the most sensitive nerve (75%), with prolonged tibial F-wave as the most sensitive parameter (72%). Sural NNT recordings were more sensitive (66%) than surface recordings (49%) (p < 0.05), however, dorsal sural (68%) and medial planter (70%) nerves had similar sensitivities as NNT. There was no side difference in the incidence of abnormality for any nerve. Based on these results, we recommend a strategy starting with tibial and sural NCS on one side for electrophysiological screening for distal symmetric PNP. If one of these is abnormal, we recommend examining the other lower and upper extremity nerves, including distal sensory nerves, particularly if NNT is not applicable. While one abnormal parameter is sufficient to interpret a nerve as abnormal, we recommend at least two abnormal nerves for PNP diagnosis, preferentially one being the sural nerve. We believe that the strategies recommended in this study may improve PNP electrodiagnosis.