Between genetics and biology. Is ENMG useful in peripheral neuropathy diagnosis and management?

Neurography and EMG are complementary techniques used in the diagnosis and monitoring of neuropathies. Both assess function of the peripheral nervous system and provide clinically useful information regarding the functional status of peripheral nerves. This information is not readily obtainable using biochemical, genetic or imaging techniques. I will discuss the role of these techniques in the diagnosis and management of neuropathies and some limitations of these techniques. These methods are routinely used in an EMG lab. These are most useful when used in conjunction with clinical examination to answer a well-defined clinical question. Reference values are required for interpretation of the data.

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.

Quantitative sensory testing in patients with polyneuropathy and healthy individuals.

AIMS: Elderly individuals and patients with polyneuropathy often feel heat pain or burning sensation on quantitative sensory testing (QST) of warm perception distally in the lower limbs. We therefore studied heat pain threshold (HPT), warm perception threshold (WPT) and the difference between heat pain and warm perception thresholds in 48 patients with symptoms and signs of polyneuropathy matched according to age and gender with 48 healthy persons. METHODS: QST (using method of limits) was performed on the distal calf and the dorsal foot. RESULTS: Particularly in the neuropathy group several individuals (58%) had an unpleasant feeling, often burning, when the thresholds according to the WPT algorithm were recorded. Difference between heat pain and warm perception thresholds in the lower calf of the patients was 3.9 +/- 3.5 and 5.8 +/- 3.4 degrees C in the controls (P = 0.012), and on the foot 3.8 +/- 2.8 vs 5.3 +/- 3.6 degrees C (P = 0.02). CONCLUSIONS: When performing QST it is important to assess also quality features of warm perception, such as burning and heat pain sensation.

Recognising F-response interference as a source of increased jitter in stimulated single fibre EMG.

OBJECTIVE: To determine the source of an abnormal pattern of latency shifts leading to falsely high jitters in single fibre electromyography (SFEMG). METHODS: We observed a sudden shortening of the latency to an individual single fibre spike component followed by a gradual return to baseline values during stimulation single fibre electromyography (SFEMG) of the facial muscle. The pattern could be reproduced in healthy controls. RESULTS: The sudden decrease in latency proved to follow an additional discharge of the muscle fibre, not due to the external stimulus. This additional discharge was identified as an F-response. CONCLUSIONS: The mechanism is thought to be a higher muscle fibre conduction velocity resulting from a temporary increase in stimulus frequency, in the form of an extra impulse along the muscle fibre represented by the F-response. SIGNIFICANCE: The typical abnormal pattern should be recognised because it can falsely increase the mean jitter. We advice to increase the time base to 50 ms if this pattern is observed and to exclude the affected potentials from jitter measurements.

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.

EFNS guideline on diagnosis and management of post-polio syndrome. Report of an EFNS task force.

Post-polio syndrome (PPS) is characterized by new or increased muscular weakness, atrophy, muscle pain and fatigue several years after acute polio. The aim of the article is to prepare diagnostic criteria for PPS, and to evaluate the existing evidence for therapeutic interventions. The Medline, EMBASE and ISI databases were searched. Consensus in the group was reached after discussion by e-mail. We recommend Halstead's definition of PPS from 1991 as diagnostic criteria. Supervised, aerobic muscular training, both isokinetic and isometric, is a safe and effective way to prevent further decline for patients with moderate weakness (Level B). Muscular training can also improve muscular fatigue, muscle weakness and pain. Training in a warm climate and non-swimming water exercises are particularly useful (Level B). Respiratory muscle training can improve pulmonary function. Recognition of respiratory impairment and early introduction of non-invasive ventilatory aids prevent or delay further respiratory decline and the need for invasive respiratory aid (Level C). Group training, regular follow-up and patient education are useful for the patients' mental status and well-being. Weight loss, adjustment and introduction of properly fitted assistive devices should be considered (good practice points). A small number of controlled studies of potential-specific treatments for PPS have been completed, but no definitive therapeutic effect has been reported for the agents evaluated (pyridostigmine, corticosteroids, amantadine). Future randomized trials should particularly address the treatment of pain, which is commonly reported by PPS patients. There is also a need for studies evaluating the long-term effects of muscular training.

Human botulism studied with single-fiber electromyography.

In two cases of mild human botulism, conventional electromyography (EMG) was normal. In one case, the investigation with reptitive nerve stimulation showed slightly abnormal results, but in the other case the findings were within normal limits. Single-fiber EMG showed abnormal neuromuscular function and at later investigations as well, when the patient no longer showed any muscular fatigability. The jitter was frequency dependent and decreased with higher innervation frequency. The single-fiber EMG findings normalized after three months. The results are in agreement with the known disturbance of acetylcholine release.

Myasthenic syndrome studied with single fiber electromyography.

A patient with the myasthenic syndrome was investigated with single fiber electromyography (SFEMG). It was found that 35 of 36 potential pairs had increased "jitter" and that 29 of these demonstrated impulse blockings. There was improvement in neuromuscular transmission with higher rates of innervation. Transmission worsened following rest. The SFEMG findings at the motor end-plate level correlate well with the results of repetitive stimulation and in vitro studies.

Myasthenia gravis with features of the myasthenic syndrome. An investigation with electrophysiologic methods including single-fiber electromyography.

A 47-year-old woman had myasthenia gravis with only moderate weakness and a consistently poor response to anticholinesterase medication. She was investigated with routine electrophysiologic studies and single-fiber electromyography. The studies showed a limited effect of anticholinesterase medication. There was a decrement to 2 Hz stimulation of not less than 25 percent regardless of medication and administration of edrophonium. With faster rates of stimulation (10 to 20 Hz), there was a facilitation up to 190 percent. In addition, with postcontractive or post-tetanic potentiation the action potential in the abductor digiti minimi muscle was increased from the initial value of 2.5 mv or less to up to 6 mv. Single-fiber electromyographic investigations showed increased jitter and blocking with little response to drugs, as well as facilitation in a large number of motor end-plates in association with both voluntary activity and repetitive stimulation. The findings indicated a mixture of phenomena seen in myasthenia gravis and the myasthenic syndrome.

Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord: an experimental study in the rat.

The potential efficacy of indomethacin (a potent inhibitor of endogenous prostaglandin synthesis) on spinal cord-evoked potentials and edema formation occurring after a focal trauma to the spinal cord was examined in a rat model. The spinal cord evoked potentials were recorded in urethane-anesthetized male rats using monopolar electrodes placed epidurally over the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral right tibial and sural nerves. Reference electrodes were placed in the corresponding paravertebral muscles. The spinal cord evoked potential consisted of a small positive peak followed by a broad and high negative peak. Amplitudes and latencies of the maximal positive peak and the maximal negative peak were measured. The latencies and amplitudes 30 min before injury were used as references (100%). A complete loss was denoted as 0%. All the potentials were quite stable during 30 min of recording before injury. Infliction of trauma to the T10-T11 segments of the spinal cord with a sterile scalpel blade (about 5 mm longitudinal and 2 mm deep incision into the right dorsal horn extending to Rexed's laminae VII) in untreated animals resulted in an immediate depression of the rostral maximal negative peak amplitude (60-100%) which persisted during 5 h of recording. The latencies of the rostral as well as caudal maximal negative and positive peaks increased successively from 2 h post-trauma. In this group of animals, 5 h after injury the spinal cord water content in the traumatized segments was increased by more than 6% as compared with a group of uninjured animals. Pretreatment with indomethacin (10 mg/kg body weight i.p. 30 min before injury) markedly attenuated the immediate decrease in the maximal negative peak amplitude after injury, but did not influence the successive latency increase. However, the increase in the water content of the traumatized cord after 5 h was less pronounced compared with untreated injured rats. Our results show a beneficial effect of indomethacin on trauma-induced spinal cord evoked potential changes and edema formation. Prostaglandins may thus influence early bioelectrical changes occurring in traumatized spinal cord not reported earlier. The findings support the view that early recording of spinal cord evoked potential may be useful to predict the outcome in some forms of spinal cord injuries.

Impairment of blood-brain barrier function by serotonin induces desynchronization of spontaneous cerebral cortical activity: experimental observations in the anaesthetized rat.

The possibility that elevation of serotonin in the circulation, which is found in various pathological states, influences the spontaneous cerebral cortical activity was examined in a rat model. The electroencephalogram was recorded using bipolar epidural electrodes placed over the frontal and parietal cerebral cortex. Intravenous infusion of serotonin (10 micrograms/kg per min for 10 min) decreased the electroencephalogram amplitude in both frontal and parietal recordings within 4 min of infusion. This decrease in amplitude was reversible, Pretreatment with cyproheptadine (a potent serotonin2 receptor antagonist) prevented the serotonin-induced decrease of the electroencephalogram amplitude. The blood-brain barrier permeability to Evans Blue and [131I]sodium was increased in frontal and parietal cortex. This increase in blood-brain barrier permeability was absent in animals pretreated with cyproheptadine. These results provide direct evidence that an elevated level of serotonin in blood has the capacity to influence spontaneous cortical electrical activity. This effect of serotonin on electroencephalogram appears to be due to its ability to enter into the brain parenchyma by inducing a short-term breakdown of the blood-brain barrier, probably via serotonin2 receptors.

Opioid receptors influence spinal cord electrical activity and edema formation following spinal cord injury: experimental observations using naloxone in the rat.

The possibility that opioid peptides participate in alteration of spinal cord conduction following trauma to the cord was investigated in a rat model using a pharmacological approach. Spinal cord injury was produced in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of T10-11 segments (2 mm deep and 5 mm long). Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. SCEP from both rostral and caudal segments consisted of a small positive peak followed by a high negative peak. Infliction of trauma in untreated rats resulted in an immediate depression of the rostral maximal negative peak (MNP) amplitude. This depression was long-lasting. Later, a significant increase in the latency of the rostral MNP amplitude occurred. Naloxone was administered in a high dosage (10 mg/kg, i.p.) to block mu-, delta- and kappa-opioid receptors 30 min before injury. This drug treatment inhibited the immediate post-injury decrease of the rostral MNP amplitude without any significant effect on latency changes. Measurement of water content in the traumatized spinal cord segment showed a significant reduction in the drug treated animals 5 h after trauma (71.46 +/- 0.54) as compared with untreated controls (74.65 +/- 0.76). However, 1 mg or 5 mg/kg dosages of the drug were not effective in reducing the SCEP changes or edema after injury. These results strongly suggest that blockade of kappa-opioid receptors with high doses of naloxone is important in reduction of trauma induced alteration of SCEP and edema formation in spinal cord injury.

The study of normal and abnormal neuromuscular transmission with single fibre electromyography.

The use of single fibre electromyography (SFEMG) in the study of neuromuscular transmission across individual motor endplates in situ is reviewed. The neuromuscular jitter can be studied both during voluntary contraction and electrical activation of the muscle fibre. The differences, pitfalls and advantages of these methods are discussed. Findings in myasthenia gravis and other disorders of the neuromuscular transmission are examined.

Pre-movement facilitation of motor-evoked potentials in man during transcranial stimulation of the central motor pathways.

Motor evoked potentials (MEPs) following trans-cranial stimulation (TCS) through unifocal electric or magnetic impulses have been evaluated in the pre-movement period in 8 healthy volunteers. By utilizing a simple reaction time paradigm, progressive amplitude increments and latency decrements of MEPs have been demonstrated in the 100 ms preceding the onset of EMG activity in the muscle examined. By employing surface and depth recordings from various muscles of hand and forearm contralateral to the TCS, it was observed that in the 'early' period of pre-EMG facilitation (100-60 ms before EMG onset) TCS solely recruited the same low-threshold motor units which are fired first during self-paced contractions. In the 'middle and late' epochs of pre-EMG facilitation, TCS served when MEPs were recorded from a relaxed muscle, during TCS of progressively higher intensity. Multiple muscle recordings showed that pre-EMG facilitation was remarkably limited to the muscular group of the hand primarily involved in the intended movement.

Neuromuscular involvement in primary hyperparathyroidism.

Sixteen consecutive patients with primary hyperparathyroidism (HPT) were examined by a combination of electrophysiological, morphological and biochemical measurements. Six patients had, preoperatively, subjective impairment of neuromuscular function. Three of them were improved by the normalization of parathyroid function after surgery. In the other patients, who either had vague symptoms or appeared to be asymptomatic, the operation did not cause subjective changes in their neuromuscular function during a 3-month follow-up period. Altogether seven patients, three of whom had symptoms, had impairment of the neuromuscular transmission as evaluated by the single-fibre EMG technique. The changes were of slight degree and unlikely to be of clinical importance. Two patients had a slightly reduced nerve conduction velocity and in two cases moderate abnormalities were found in muscle biopsy specimens. In conclusion, the muscular weakness reported by HPT patients did not seem to be caused by disturbance of neuromuscular transmission. HPT patients who preoperatively were apparently asymptomatic did not have defects of their neuromuscular transmission that were of clinical significance.

Simulation of the normal concentric needle electromyogram by using a muscle model.

OBJECTIVES: To study the correlation between anatomical parameters and EMG signals by means of simulations. METHODS: A mathematical model of the electrical activity from muscle fibres and motor units has been developed. The electrical fields around the muscle fibres are simulated using a line source model. The model permits the simulation of single muscle fibre action potentials obtained by SFEMG, concentric and Macro EMG electrodes. By using appropriate anatomical parameters EMG recordings with these electrodes can be simulated. The model is flexible and permits a number of anatomical parameters to be changed such as; number of muscle fibres in a motor unit, fibre diameter distribution, and motor end-plate geometry. Some physiological parameters can be optionally varied; firing rate, threshold for recruitment, jitter. RESULTS: In this study, simulations of CNEMG are performed and the influence of a number of parameters on the CNEMG signal is studied. It is shown that the model produces motor unit potentials reasonably well resembling those from live recordings. More important is however the relative change in MUP parameters when certain conditions are changed; number of muscle fibres in a motor unit, recording position, muscle fibre diameters and some special effects of the recording conditions. CONCLUSIONS: The simulated muscle and corresponding EMG recording can be used both as a research tool and for teaching.

The motor nerve simulator.

OBJECTIVE: The aim of the study was to develop a mathematical model of the motor nerve and the action potentials generated from its axons, in order to simulate conditions seen in neurography. The model should be used for the detailed study of the relationship between various nerve characteristics and the electrophysiological recordings obtained. METHODS: The model was developed as a software tool. The signals from individual motor units were real recordings using conventional surface electrodes. There was good agreement between the constructed compound muscle action potential and the one recorded live for the subject from whom the individual signals were obtained. RESULT: A number of physiological characteristics can be changed, including the number of axons, their conduction properties, excitability properties, degree of proximo-distal velocity slowing. F-waves and A-waves can be generated. CONCLUSION: The model gives a good similarity to findings obtained in live recordings. A number of physiological characteristics can be studied individually, something that cannot be done in live recordings. The model can be used in teaching and in research studies of the relationship between nerve properties and neurography parameters.

Simulation of EMG in pathological situations.

OBJECTIVE: A mathematical model for simulation of the EMG from a muscle with its motor units is used. The study aims at correlating EMG findings (single-fiber EMG and concentric-needle EMG) with various induced morphological changes. METHODS: Reinnervation has been simulated by removing motor units randomly followed by a complete reinnervation from adjacent surviving motor units. Fibre type grouping and grouped atrophy can be seen. Myopathy is simulated by increased fibre diameter variation, loss of fibres and muscle fibre splitting. RESULTS AND CONCLUSION: The simulation gives quantitative aspects of the importance of each of these factors. It indicates the relative sensitivity of various EMG parameters. The model can be used both for education and for research.

Automatic carpal tunnel syndrome tester.

OBJECTIVE: A device for automatic testing of sensory latency across the carpal tunnel is described. A fixed bar contains a stimulating electrode distally and a bipolar recording set up with the two poles at 7 and 14 cm distance proximally. The device is thus based on the so called 14/7 method, using orthodromic testing. METHODS: Automatic testing of electrode resistance and muscle relaxation precedes the self triggered start of stimulation. The latencies are analyzed according to a special algorithm. The proximal/distal latency index is increased in carpal tunnel syndrome (CTS). RESULTS: Healthy controls (32 hands in 32 subjects) and patients referred with suspicion of CTS (258 hands) were studied with the new device, by conventional technique and sometimes by inching (centimetering) across the carpal tunnel. A positive CTS result with the tester was in accordance with the routine test in 94% of the patients. Conversely, routine studies showed CTS in 118 hands. Among those, the tester agreed in 44, showed no signals in 70 and indicated normal findings in 4 hands. In cases with a combination of polyneuropathy and CTS, the CTS was detected in 5 out of 6 cases. A complete test takes about 1 min per hand. CONCLUSIONS: The results are very promising.

Comparison between concentric needle EMG and macro EMG in patients with a history of polio.

OBJECTIVES: Acute poliomyelitis causes degeneration of anterior horn cells, followed by denervation. Reinnervation and muscle fibre hypertrophy are mechanisms that compensate this loss of neurones. Concentric needle EMG (CNEMG) and macro EMG are two methods to assess the magnitude of initial involvement and the compensatory reinnervation. The aim of this study is to explore the difference between CNEMG and macro EMG describing the status of the motor unit in patients previously affected by polio. METHODS: Macro and concentric needle EMG investigations were performed in 261 muscles in 121 patients with a remote history of polio. RESULTS: CNEMG was abnormal in 211 muscles, macro EMG was abnormal in 246 muscles. The macro amplitude was 3-4 times 'more abnormal' than CNEMG amplitude relative to the reference values. CNEMG duration was less abnormal and showed only weak correlation with macro amplitudes. The most likely explanation for the difference in magnitude of deviation from reference values for CNEMG and macro EMG, is a more pronounced 'phase cancellation' between single fibre action potentials in CNEMG. This is supported by simulation studies reported here. CONCLUSIONS: In conclusion macro EMG better reflects the size of the motor unit than the CNEMG. For detection of concomitant disorders, CNEMG is the method of choice.