Erik Stålberg

Quantitative analysis of individual motor unit potentials: a proposition for standardized terminology and criteria for measurement

The physiology of the motor unit potential (MUP) is reviewed. The aim is to identify the electrophysiological events in the motor unit that generate the individual parts of the MUP. This is based on insight gained from new experimental techniques, such as single-fiber electromyography (EMG), scanning EMG, and simulation studies of the MUP. A terminology for the different parts of the MUP is also suggested, and nine parameters used to describe different features of the MUP are delineated: duration, spike duration, amplitude, area, spike area, phases, turns, satellites, and variability. Technical aspects, such as electrode type, filtering, and sampling rate of the computers, are discussed as well. In Appendix A, different manual and computer-aided methods for quantitative MUP analysis are described. Despite minor systematic differences between the methods, MUP durations measured by different methods correlate highly with each other (Appendix B). The manual and computer-aided methods have comparable variability between repeated measurements.

Automatic analysis of the emg interference pattern

A method is described for the automatic analysis of EMG interference patterns obtained at optional non-controlled force levels. It is a modification of Willisons method of measuring turns and amplitude of the signal. In the method, the mean amplitude is plotted against turns obtained during 300 msec for each of 20 recording sites. Different voluntary strengths are used and a scatter of points is obtained. Confidence limits enclosing these points are constructed for healthy subjects for 4 different muscles with concentric and monopolar electrodes. The normal values differ with age, muscle, sex and electrode. The method is tested on patients with myopathic or neurogenic EMG and a high diagnostic yield is obtained. The method is objective, reproducible, fast and needs relatively small computer facilities.

Effects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluation.

Four monkeys were exposed to a total of 8 g each of manganese as oxide by repetitive subcutaneous injections during 5 months, after which they were left for 1 week to 6 months before they were sacrificed. All animals developed hyperactive behaviour after about 2 months. About 5 months after the start of the exposure the animals became hypoactive with an unsteady gait, and subsequently an action tremor appeared in some of the animals. The animals lost power in both upper and lower limbs and the movements of the hands and feet were very clumsy. The serum content of manganese rose 10–40 times during the exposure time and the content in brain was generally increased more than 10 times, with the highest content found in globus pallidus and putamen. The observed neurochemical effects were also largest in globus pallidus and putamen. In these regions there was a considerable depletion of dopamine and 3,4-dihydroxyphenylacetic acid, while the homovanillic acid content remained almost unchanged. A severe neuronal cell loss was observed in globus pallidus but not in other regions. This is in accordance with results from the most recent neuropathological study of a human suffering from chronic manganese poisoning [Yamada et al. (1986) Acta Neuropathol 70: 273–278] where globus pallidus was devoid of neuronal cells while the content of pigmented cells in substantia nigra was normal. Our data suggest a reduction in number of dopaminergic nerve terminals, as the activity of the dopamine synthesizing enzyme DOPA-decarboxylase was also lowered. In addition to the effects on the dopaminergic system, a reduced content of 5-hydroxyindole acetic acid was observed in the putamen and globus pallidus. Moreover neurotensin, a neuropeptide with functional connection to the dopaminergic system, was found to be reduced in the putamen. It was remarkable that all the neurochemical effects seen in the putamen were more or less absent from the caudate nucleus. These observations are discussed in relation to what has been found in Parkinsonian and MPTP-lesioned brains.

Comparison of quantitative techniques in anal sphincter electromyography.

Data comparing results and utility of different quantitative electromyographic (EMG) techniques are limited. In the present study, we analyzed the EMG signal from the external anal sphincter (EAS) muscle using three techniques of motor unit potential (MUP) analysis, and a technique of interference pattern (IP) analysis. We examined 56 patients with damage to the cauda equina or conus medullaris, and 64 control subjects. Using manual‐MUP and multi‐MUP analysis about 20 MUPs, using a single‐MUP technique about 10 MUPs, and using turn/amplitude (T/A) analysis about 20 IP samples were obtained. The sensitivities of these techniques in distinguishing neuropathic from control muscles were calculated. The single‐MUP technique detected 63%, manual‐MUP 57%, and multi‐MUP analysis 62% of neuropathic muscles, and MUP parameters obtained by each of these differed significantly from the other. The sensitivity of T/A analysis of IP was 29%. Our results confirm the need for separate MUP normative data for each of the MUP analysis techniques, and favor them over the IP analysis technique. The normative data presented for the EAS muscle should improve and promote quantitative EMG in patients.

Analysis of the electromyographic interference pattern.

The electromyographic interference pattern (EMG-IP) contains information about the number, firing rate, and recruitment characteristics of motor units, and information regarding the waveforms of the recruited motor units. Muscle and nerve diseases produce characteristic changes in the IP that can be distinguished by IP analysis. This analysis complements analysis of the motor unit potentials. The electromyographer usually assesses the IP signals subjectively by their appearance on the oscilloscope screen and by their sound on the audio monitor. Techniques have been developed to automate IP analysis with and without force monitoring. These techniques give objective information, quantitate the degree of abnormality, and permit electromyographers-in-training to compare their subjective analysis of the IP with more objective findings.

Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected correlation between the mutated gene and the associated phenotype. This provides a good rationale for examining patients with apparent distal myopathy for a neuromuscular transmission disorder and agrin mutations.

Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis

The aim of this prospective study was to assess whether extra discharges (EDs), sometimes following the compound muscle action potential, could be used as a neurophysiological indicator of overdose of acetylcholinesterase inhibitors (AChEIs) in patients with myasthenia gravis (MG). The characteristics and frequency of EDs were explored and the correlation of EDs with cholinergic side effects was also determined. Twenty‐two MG patients (14 women, 8 men; 61 ± 16 years of age) with daily AChEI treatment were examined. The mean disease duration was 10 years (range 2–62 years) and all patients had been treated with AChEI since MG onset. Both single and repetitive stimulation of the ulnar and accessory nerves were performed before and 60 min after oral pyridostigmine bromide (PB) administration and after additional edrophonium injection. Fatigue, side effects, and AChE activity in blood were assessed before and 60 min after PB intake. The daily dose of PB ranged from 150 to 900 mg/day. Fourteen patients (64%) experienced daily cholinergic adverse effects, and muscarinic side effects correlated with AChE activity. Eleven patients (50%) developed EDs after oral PB. Among the eight patients with daily nicotinic side effects, EDs were significantly (P < 0.05) more common. Additionally, older patients were more prone to develop cholinergic side effects and EDs. Thus, when EDs are found, patients should be asked about daily muscular symptoms, which may be related to AChEI treatment and not solely to MG. Muscle Nerve, 2007

Macro electromyography and motor unit number index in the tibialis anterior muscle : Differences and similarities in characterizing motor unit properties in prior polio

Our objective was to establish the usefulness of the noninvasive method of the motor unit number index (MUNIX) in a large muscle and to study how macro electromyography (EMG) and MUNIX complement each other in describing the motor units (MUs) in prior polio. MUNIX and macro EMG were performed in 48 tibialis anterior muscles in 33 prior polio patients. In addition, the reproducibility of MUNIX was investigated. It is shown that MUNIX can be used to characterize MUs with high reproducibility, even in a large muscle. As judged by MUNIX values, the patients had a 25% reduction of motor neurons, whereas the macro EMG indicated a loss of 60% of the neurons. Macro EMG showed more pronounced changes compared with control material than the MUNIX. One of the reasons for this finding may be the difference in MU populations studied with the two methods. Muscle Nerve, 2011

Polyneuropathy in type 1 and type 2 diabetes: comparison of nerve conduction studies, thermal perception thresholds and intraepidermal nerve fibre densities

To evaluate possible differences in distal polyneuropathy (PN) characteristics and degree of abnormalities for various small and large fibre parameters in diabetes type 1 (DM1) and type 2 (DM2).

Acetylcholinesterase inhibitors in MG: To be or not to be?

Myasthenia gravis (MG) is an autoimmune disorder usually caused by antibodies against either the acetylcholine receptor (AChR) or muscle‐specific tyrosine kinase (MuSK) at the neuromuscular junction. Neuromuscular transmission failure results in muscle fatigue and weakness that can be treated symptomatically with acetylcholinesterase inhibitors (AChEIs). Long‐term treatment with nonselective AChEIs may have considerable drawbacks; thus, this medication is ideally tapered when strength improves. Patients with AChR antibodies respond beneficially to treatment, whereas patients with MuSK antibodies generally do not. Recently, the selective AChEI EN101, which specifically targets the isoform of “read‐through” AChE (AChE‐R), has been developed and may be of importance for symptomatic relief in AChR‐antibody seropositive MG. This article is a review of the mechanisms, therapeutic effects, and drawbacks, with both old and new AChEIs in MG. Muscle Nerve, 2009