Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate.

Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins.

Validation of the Swedish version of the disease-specific Myasthenia Gravis Questionnaire.

The aim of this study was to translate and validate the disease-specific patient-derived Myasthenia Gravis (MG) Questionnaire to enable use among Swedish MG patients. The original Italian version of the MG Questionnaire (MGQ) was translated into Swedish and transculturally adapted. The validity and reliability was tested on 48 Swedish MG patients. We correlated MGQ scores with disease severity and with the Swedish version of the Short-Form 36-item general health survey (SF-36). Reproducibility was assessed on 18 clinically stable MG patients. A significant correlation regarding the MGQ scores was seen when correlated with physical scores of the SF-36 and the overall clinical status. Internal consistency and reproducibility was excellent. We conclude that the evaluation capacities of the Swedish MGQ are equivalent to those of the original Italian version of the MGQ. The questionnaire was successfully validated as an outcome measure also for Swedish MG patients, which is important for international multicentre clinical trials.

Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes.

OBJECTIVE: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes. METHODS: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative and single-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens with histological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear gene POLG1 was sequenced. RESULTS: Five AChR-Ab seropositive [AChR(+)] and 5 seronegative [AChR(-)] patients were MuSK-Ab seropositive [MuSK(+)]. Five of 7 neurophysiologically examined MuSK(+) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(-)/AChR(+) patients (23%) (P=0.012). SFEMG was abnormal in all examined MuSK(+) patients. All 7 biopsied MuSK(+) and 32 MuSK(-) patients (89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(+) and 13 of 20 MuSK(-) patients analyzed had multiple mtDNA deletions but no POLG1 mutations. CONCLUSIONS: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(+) and AChR(+) patients. Proximal myopathy was over-represented in MuSK(+) patients; however, both MuSK(+) and MuSK(-) patients had mild myopathy with frequent mitochondrial abnormalities. SIGNIFICANCE: The weakness in MuSK(+) patients is most likely due to disturbed neuromuscular transmission. The frequently encountered mitochondrial dysfunction in MG warrants further study.

Correlation between regional myasthenic weakness and mental aspects of quality of life.

Here we report how the different types of regional muscle involvement, i.e. bulbar, ocular or generalized, in patients with myasthenia gravis (MG) influence the mental aspects of quality of life. Clinical examination according to Osserman was performed in 48 MG patients (45 women, three men; mean age 54, SD 12 years). Each patient was at the time for clinical evaluation asked to fill out the disease-specific Myasthenia Gravis Questionnaire (MGQ) and the Short-Form 36-item questionnaire for health survey (SF-36) as patient-oriented tools. We related the regional domains (generalized domain, bulbar domain and ocular domain) of the MGQ and the clinical findings, respectively, with mental quality of life as assessed by SF-36. Bulbar and generalized involvement results in impairment of mental aspects of quality of life, whereas ocular involvement does not.

Some observations on fibrillations and positive sharp waves.

Electromyographic recordings of fibrillation potentials (FPs) and positive sharp waves (PSWs) demonstrate transformation of FP to PSW and vice versa, atypical firing patterns, changes in waveform shape and amplitude, and time-locked potentials. The etiology of the waveform characteristics of FP and PSW is discussed based on abnormal propagation in a small section of muscle fiber that is "damaged" by the needle. The results of simple computer simulations are described.

Predictive value of single-fiber electromyography in the extensor digitorum communis muscle of patients with ocular myasthenia gravis: a retrospective study.

PURPOSE: To determine if the jitter in the extensor digitorum communis (EDC) muscle in patients with purely ocular myasthenia gravis (OMG) predicts the subsequent development of generalized myasthenic weakness-Methods: Included in this retrospective study were patients who initially had purely ocular manifestations and had been followed for at least 2 years after onset of myasthenic symptoms. The group consisted of 50 patients with purely ocular weakness, 26 of whom later generalized. All underwent single-fiber electromyography (SFEMG) studies in the EDC muscle at the initial examination RESULTS: : Statistical analysis did not demonstrate that the amount of jitter in the EDC muscle predicted the development of generalized myasthenia gravis (GMG). Also, there was no threshold jitter value that predicted generalized weakness. CONCLUSIONS: : SFEMG measurement of jitter in the EDC muscle demonstrates abnormal neuromuscular transmission in many patients with OMG but is not useful in predicting generalization in these patients.

Motor unit size estimation of enlarged motor units with surface electromyography.

Surface EMG is hardly used to estimate motor unit (MU) characteristics, while its non-invasiveness is less stressful for patients and allows multi-electrode recordings to investigate different sites of the muscle and MU. The present study compares motor unit potentials (MUPs) obtained with surface EMG and macro EMG during voluntary contraction of the biceps brachii muscle of patients with enlarged MUs caused by prior poliomyelitis. Averaged surface MUPs were obtained by means of needle EMG (SMUP1) and surface EMG (SMUP2) triggering. The MUPs area and peak amplitudes correlated well when comparing the macro MUP and SMUP1 of the same MUs. When MU populations of different patients were compared, the SMUP1s and SMUP2s were equally sensitive to pathology as macro MUPs. In this, the late non-propagating positive wave (only present in unipolar recordings) is more robust than the triphasic propagating wave. Therefore, surface EMG can be used for detecting enlarged MUs.

Motor unit size estimation: confrontation of surface EMG with macro EMG.

Surface EMG (SEMG) is little used for diagnostic purposes in clinical neurophysiology, mainly because it provides little direct information on individual motor units (MUs). One of the techniques to estimate the MU size is intra-muscular Macro EMG. The present study compares SEMG with Macro EMG. Fifty-eight channel SEMG was recorded simultaneously with Macro EMG. Individual MUPs were obtained by single fiber triggered averaging. All recordings were made from the biceps brachii of healthy subjects during voluntary contraction at low force. High positive correlations were found between all Macro and Surface motor unit potential (MUP) parameters: area, peak-to-peak amplitude, negative peak amplitude and positive peak amplitude. The MUPs recorded with SEMG were dependent on the distance between the MU and the skin surface. Normalizing the SEMG parameters for MU location did not improve the correlation coefficient between the parameters of both techniques. The two measurement techniques had almost the same relative range in MUP parameters in any individual subject compared to the others, especially after normalizing the surface MUP parameters for MU location. MUPs recorded with this type of SEMG provide useful information about the MU size.

AAEM minimonograph #25: single-fiber electromyography.

Single-fiber electromyography (SFEMG) is a selective recording technique in which a needle electrode with a small recording surface in the side is used to identify action potentials from individual muscle fibers. The SFEMG parameters of greatest clinical use are fiber density (FD) and neuromuscular jitter. FD reflects the local organization of muscle fibers within the motor unit; jitter reflects the safety factor of neuromuscular transmission at individual neuromuscular junctions. SFEMG can be of great value in demonstrating or excluding abnormalities in mild or questionable disease of nerve, muscle, or the neuromuscular junction. The neuromuscular jitter may be measured during nerve stimulation, which is particularly useful in uncooperative patients or when it is desirable to control the firing rate precisely, or during voluntary muscle activation, which is less subject to technical artifact. The SFEMG findings may not be specific to a particular disease, but they frequently increase understanding of the disease process by demonstrating abnormal neuromuscular transmission or rearrangement of muscle fibers within the motor unit, which complements information from more conventional EMG examinations.

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.

Multiple innervation of muscle fibers in myasthenia gravis.

Single fiber EMG recordings from patients with myasthenia gravis obtained during axonal microstimulation revealed an occasional bimodal distribution of response latencies. This phenomenon could be dependent on stimulus strength, however, in a way different from that in the axon reflex. It is suggested to be due to dual neuromuscular junctions (NMJs) supplied by two different motor neurons. Some cases of bimodal jitter were not dependent on stimulus strength and are assumed to be due to dual innervation by the same neuron. The phenomenon could only be demonstrated at abnormal NMJs with partial impulse blocking. It is suggested to reflect multiple reinnervation of muscle fibers that had undergone functional or structural denervation in the course of the immune attack against the original NMJ. This study suggests that the coexisting NMJs from the same or different motor neurons may be functional at the same time.

Assessment of variability in the shape of the motor unit action potential, the "jiggle," at consecutive discharges.

A method for quantifying shape variability, the jiggle, or motor unit potentials (MUPs) recorded with conventional EMG electrodes is presented. Amplitude variability at each point of time of the MUP was analyzed. Two new parameters are proposed: the normalized value of the consecutive amplitude differences (CAD), and the cross-correlational coefficient of the consecutive discharges (CCC). Simulations showed that increased jitter of the constituent single fiber potentials increases the jiggle as expressed by an increase in CAD and decrease in CCC values. Even when the jitter value of each component was fixed, increased temporal dispersion increased the jiggle whereas an increased number of fibers decreased the jiggle. This new method has been applied in normal subjects, patients with chronic neurogenic diseases and patients with ALS. Jiggle was significantly increased in the ALS group, in agreement with visual observations. We believe that this method for quantifying jiggle will increase the information obtainable from routine EMG investigations.

On the shape of the normal turns--amplitude cloud.

Factors that affect the shape of the so-called "normal cloud" of the turns and amplitude measurements of the electromyographic interference pattern are investigated. As the force of voluntary contraction increases from low to moderate levels, the number of turns in the signal increase faster than does the mean amplitude change between turns. This results in a cloud that is concave downward. At higher force levels, the pattern is reversed. The overall shape of the cloud thus depends on the maximum effort at which recordings are made, which is determined by the procedure of muscle activation.

Automatic analysis of heart rate variation: II. Findings in patients attending an EMG laboratory.

An automatic method was used to measure the heart rate variation with breathing in patients with different neuromuscular conditions attending a laboratory of electromyography (EMG). The objective was to determine the frequency of abnormalities in various conditions and the relationship between R-R variation and different nerve conduction parameters. The percentages of reduced R-R variation were 73% in diabetics, 35% in Guillain-Barré syndrome, 22% in amyotrophic lateral sclerosis, and 50% in amyloidosis. R-R variation in diabetics was significantly correlated to most parameters of nerve conduction. In Guillain-Barré syndrome it correlated significantly with the ulnar and median M-response amplitudes. Most patients with myopathies showed normal R-R variation.

Automatic analysis of heart rate variation: I. Method and reference values in healthy controls.

Many patients referred to an electrophysiological laboratory may have autonomic dysfunction. Some parasympathetic tests are based on the assessment of heart rate variation induced by breathing, Valsalva maneuver, and standing. We have developed fast and practical computer-based methods to analyze heart rate variation using standard EMG equipment and a personal computer. For quantitative description we have evaluated different algorithms, both earlier described and new ones. Findings in patients with diabetes have been compared with those obtained from healthy subjects in order to determine the diagnostic utility of the various algorithms. The optimal algorithm has been chosen by this and other criteria, and a reference database from healthy subjects has been developed.

Single-fiber EMG study of the flexor carpi radialis H reflex.

Late responses were studied in the flexor carpi radialis muscle by surface-recording and single-fiber electromyography. By single-fiber studies we were able to distinguish 2 distinct components. One was an H reflex obtained without a preceding M response and with a stimulus response jitter of about 100 musec; its latency was shortened and jitter decreased with the Jendrassik maneuver. The other was an F wave always preceded by an M response and with a stimulus response jitter of under 50 musec; its jitter and latency are unaffected by the Jendrassik maneuver. At the single-fiber level it was possible to determine the rate of occurrence of individual H reflexes and F responses for a given number of surface-applied stimuli. The H reflex had a very high rate of occurrence (up to 97%), whereas the F wave occurred very infrequently (less than 2% of the time). Using the H reflex rate of occurrence in conjunction with the maximal surface H/M amplitude ratios allowed us to determine the proportion of alpha motor neurons which participate in the H-reflex generation. The study of H-reflex jitter gives an estimate of the central synaptic jitter and effectiveness of the spatial and temporal summation of type 1a fiber inputs on the motor neurons.

EMG of reinnervated motor units: a simulation study.

Using computer simulation techniques, reinnervation of motor units (MUs) was studied by increasing the number of muscle fibers in the MU without changing the MU territory. The fiber density (FD) measured by single fiber EMG electrodes, the amplitude, area and number of turns of concentric needle (CN) EMG motor unit action potentials (MUAPs) and the amplitude of macro EMG MUAPs were most affected by partial reinnervation changes. The values of these features increased during simulated advanced reinnervation, as did the number of CNEMG MUAPs that had increased numbers of phases or turns and the mean CNEMG MUAP duration. The increase in macro EMG MUAP amplitude, FD and CNEMG MUAP area were proportional to the increase in the number of muscle fibers in the MU. When loss of muscle fibers due to so-called MU fractionation was simulated, values of all EMG features fell, but were still increased compared to normal. Two patterns of change in SFEMG and macro EMG values were identified that may distinguish between recordings made from reinnervated low force threshold MUs and those from higher force threshold MUs.

Analysis of amplitude and area of concentric needle EMG motor unit action potentials.

Computer simulations indicate that measurements of the area of motor unit action potentials (MUAPs) recorded with a concentric needle electrode could be useful in differentiating between neuropathy and myopathy. However, MUAP area varies markedly when the position of the recording electrode is changed only slightly within the motor unit territory, mainly because of the changes in the MUAP amplitude produced by only slight electrode movements. The ratio of MUAP area to amplitude is much less affected by changes in electrode position and measures the 'thickness' of the MUAP wave form. We found that the MUAP area:amplitude ratio was reduced in myopathy even when the MUAP amplitude was normal or increased. In patients with neuropathy, the MUAP amplitude and area both tend to be increased while their ratio is normal or increased. The diagnostic yield obtained from MUAP area, amplitude and their ratio in combination was similar to that obtained using measurements of MUAP duration. Unlike the MUAP duration, the MUAP area, amplitude and area:amplitude ratio are robust features of the MUAP in that they are less sensitive to the signal-to-noise ratio and inter-operator differences in signal selection.