Familial continuous motor unit activity and epilepsy

A mother and son both had muscle stiffness due to continuous generalized muscle twitching, beginning in childhood and associated with epileptic seizures. Electromyography (EMG) showed continuous motor unit activity (CMUA) at rest, which decreased during ischemia, sleep, and carbamazepine treatment, and was abolished by anesthetic nerve blockade. Genetic analysis disclosed a G724C point mutation in the potassium channel KCNA1 gene. The electrophysiological data suggested pathological impulse generation in both the peripheral and central nervous system, probably related to abnormal ion channel function.     

Peripheral neuropathy with a syndrome of continuous motor unit activity

Summary A chronic alcoholic who had also been submitted to partial gastrectomy developed a syndrome of continuous motor unit activity responsive to phenytoin therapy. There were signs of minimal distal sensorimotor polyneuropathy. Symptoms of the syndrome of continuous motor unit activity were fasciculation, muscle stiffness, myokymia, impaired muscular relaxation and percussion myotonia. Electromyography at rest showed fasciculation, doublets, triplets, multiplets, trains of repetitive discharges and myotonic discharges.Trousseau's and Chvostek's signs were absent. No abnormality of serum potassium, calcium, magnesium, creatine kinase, alkaline phosphatase, arterial blood gases and pH were demonstrated, but the serum Vitamin B₁₂ level was reduced.The electrophysiological findings and muscle biopsy were compatible with a mixed sensorimotor polyneuropathy. Tests of neuromuscular transmission showed a significant decrement in the amplitude of the evoked muscle action potential in the abductor digiti minimi on repetitive nerve stimulation.These findings suggest that hyperexcitability and hyperactivity of the peripheral motor axons underlie the syndrome of continuous motor unit activity in the present case.

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Zusammenfassung Ein chronischer Alkoholiker, mit subtotaler Gastrectomie, litt an einem Syndrom dauernder Muskelfaseraktivität, das mit Diphenylhydantoin behandelt wurde. Der Patient wies minimale Störungen im Sinne einer distalen sensori-motorischen Polyneuropathie auf. Die Symptome dieses Syndroms bestehen in: Fazikulationen, Muskelsteife, Myokymien, eine gestörte Erschlaffung nach der Willküraktivität und eine Myotonie nach Beklopfen des Muskels. Das Elektromyogramm in Ruhe zeigt: Faszikulationen, Doublets, Triplets, Multiplets, Trains repetitiver Potentiale und myotonische Entladungen. Trousseau- und Chvostek-Zeichen waren nicht nachweisbar. Gleichzeitig lagen die Kalium-, Calcium-, Magnesium-, Kreatinkinase- und Alkalinphosphatase-Werte im Serumspiegel sowie O₂, CO₂ und pH des arteriellen Blutes im Normbereich. Aber das Niveau des Vitamin B₁₂ im Serumspiegel war deutlich herabgesetzt. Die muskelbioptische und elektrophysiologische Veränderungen weisen auf eine gemischte sensori-motorische Polyneuropathie hin. Die Abnahme der Amplitude der evozierten Potentiale, vom M. abductor digiti minimi abgeleitet, bei repetitiver Reizung des N. ulnaris, stellten eine Störung der neuromuskulären Überleitung dar.Aufgrund unserer klinischen und elektrophysiologischen Befunde könnten wir die Hypererregbarkeit und Hyperaktivität der peripheren motorischen Axonen als Hauptmechanismus des Syndroms dauernder motorischer Einheitsaktivität betrachten.

     

Muscle hypertrophy in multifocal motor neuropathy is associated with continuous motor unit activity

Multifocal motor neuropathy (MMN) is typically associated with distal upper limb weakness and wasting. However, proximal muscle bulk, particularly of biceps brachii, may be well preserved even in the presence of severe proximal weakness. Here we report 3 patients with MMN who had true muscle hypertrophy of severely weakened biceps muscles and positive motor symptoms including cramp and fasciculations in these muscles. Electromyographic studies demonstrated markedly impaired recruitment in the affected muscles and continuous motor unit activity comprising multiple fasciculation potentials at a frequency of up to 30 per minute. We propose that this continuous motor unit activity may have contributed to the hypertrophy in these muscles. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 479–485, 1997     

Further motor unit studies in Duchenne muscular dystrophy.

Numbers of functioning motor units have been estimated in 124 muscles of boys with Duchenne dystrophy; some of the patients were studied on several occasions. In the distal muscles examined (extensor digitorum brevis, thenar, and hypothenar muscles) the losses of units were probably present at birth and did not decrease with age. In contrast, the numbers of units and of excitable muscle fibres in the soleus muscles declined significantly, especially between the ages of 9 and 12 years.     

Neuronal type of Charcot-Marie-Tooth disease with a syndrome of continuous motor unit activity

The clinical, genetic and electrophysiological study of 3 patients with an association of a neuronal form of Charcot-Marie-Tooth Disease (CMTD) with a syndrome of continuous motor unit activity (CMUA) are reported, with light and electron microscopy of muscle and sural nerve biopsies in 2 patients. The unusual clinical features of CMTD were associated with fasciculation, cramps, myokymia, impaired muscular relaxation and percussion myotonia with their electromyographic (EMG) correspondent, responsive to valproic acid (VPA) therapy. In Case 3, an important muscle hypertrophy which was confirmed by morphometric data, was noted in addition. Nerve biopsy and electrophysiological findings indicated that axonal degeneration with secondary demyelination and remyelination underlie the hereditary motor and sensory neuropathy (HMSN) in our patients. The hyperexcitability and hyperactivity of peripheral motor axons probably induced by the hereditary neuropathy may, in this instance, be the causative condition of the syndrome of CMUA in our patients.     

Conduction block and continuous motor unit activity in chronic acquired demyelinating polyneuropathy

The term continuous motor unit activity (CMUA) may be used to refer to the involuntary, sustained activity of motor units caused by hyperactivity of peripheral motor nerves. CMUA has been reported in association with acquired neuropathies such as chronic inflammatory demyelinating polyneuropathy. The precise mechanism responsible for the excess muscle activity is not defined, but the activity is believed to originate in the peripheral nerves, perhaps at sites of focal demyelination. We describe a case of an acquired, demyelinating neuropathy associated with distal motor conduction block in which CMUA was observed in muscles innervated by blocked axons. Despite the prolonged disease duration of nearly 40 years, marked clinical and electrophysiological improvement as well as resolution of the CMUA were observed following immunosuppressive therapy. A relationship between the chronic motor conduction block and the excess muscle activity is postulated.     

Assessment of motor unit loss in patients with spinal muscular atrophy

ObjectiveTo assess motor unit (MU) changes in patients with spinal muscular atrophy (SMA) using compound muscle action potential (CMAP) scans.MethodsWe performed CMAP scan recordings in median nerves of 24 treatment-naïve patients (median age 39; range 12–75 years) with SMA types 2–4. From each scan, we determined maximum CMAP amplitude (CMAP_max), a motor unit number estimate (MUNE), and D50 which quantifies the largest discontinuities within CMAP scans.ResultsMedian CMAP_max was 8.1 mV (range 0.9–14.6 mV), MUNE was 29 (range 6–131), and D50 was 25 (range 2–57). We found a reduced D50 (<25) in patients with normal CMAP_max (n = 12), indicating MU loss and enlarged MUs due to reinnervation. Lower D50 values were associated with decreased MUNE (P < 0.001, r = 0.68, n = 43). CMAP_max, MUNE and D50 values differed between SMA types (P < 0.001). Lower motor function scores were related to patients with lower CMAP_max, MUNE and D50 values (P < 0.001).ConclusionsThe CMAP scan is an easily applicable technique that is superior to routine assessment of CMAP_max in SMA.SignificanceThe detection of pathological MU changes across the spectrum of SMA may provide important biomarkers for evaluating disease course and monitoring treatment efficacy.     

Myokymic syndrome with impaired muscular relaxation: further evidence of a possible paraneoplastic genesis

A case of concomitant myokymia with impaired muscular relaxation and hypertrophic osteoarthropathy associated with the presence of two separate lung malignancies is described. Both the neurological syndrome and osteoarticular disorder significantly improved after surgical removal of the lung cancers. The possibility that common mechanisms may underlie these two tumour-related disorders is also discussed.     

Detecting impaired muscle relaxation in myopathies with the use of motor cortical stimulation

Impaired muscle relaxation is a notable feature in specific myopathies. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly halting corticospinal drive. Our aim was to quantify muscle relaxation using TMS in different myopathies with symptoms of muscle stiffness, contractures/cramps, and myalgia and explore the technique's diagnostic potential. In men, normalized peak relaxation rate was lower in Brody disease (n = 4) (-3.5 ± 1.3 s^-1), nemaline myopathy type 6 (NEM6; n = 5) (-7.5 ± 1.0 s^-1), and myotonic dystrophy type 2 (DM2; n = 5) (-10.2 ± 2.0 s^-1) compared to healthy (n = 14) (-13.7 ± 2.1 s^-1; all P ≤ 0.01) and symptomatic controls (n = 9) (-13.7 ± 1.6 s^-1; all P ≤ 0.02). In women, NEM6 (n = 5) (-5.7 ± 2.1 s^-1) and McArdle patients (n = 4) (-6.6 ± 1.4 s^-1) had lower relaxation rate compared to healthy (n = 10) (-11.7 ± 1.6 s^-1; both P ≤ 0.002) and symptomatic controls (n = 8) (-11.3 ± 1.8 s^-1; both P ≤ 0.008). TMS-induced muscle relaxation achieved a high level of diagnostic accuracy (area under the curve = 0.94 (M) and 0.92 (F)) to differentiate symptomatic controls from myopathy patients. Muscle relaxation assessed using TMS has the potential to serve as a diagnostic tool, an in-vivo functional test to confirm the pathogenicity of unknown variants, an outcome measure in clinical trials, and monitor disease progression.     

Muscle hypertrophy and a syndrome of continuous motor unit activity in prednisone-responsive Guillain-Barré polyneuropathy

Summary The clinical, electrophysiological and morphological findings (light and electron microscopy of the sural nerve and gastrocnemius muscle) are reported in an unusual case of Guillain-Barré polyneuropathy with an association of muscle hypertrophy and a syndrome of continuous motor unit activity. Fasciculation, muscle stiffness, cramps, myokymia, impaired muscle relaxation and percussion myotonia, with their electromyographic accompaniments, were abolished by peripheral nerve blocking, carbamazepine, valproic acid or prednisone therapy. Muscle hypertrophy, which was confirmed by morphometric data, diminished 2 months after the beginning of prednisone therapy. Electrophysiological and nerve biopsy findings revealed a mixed process of axonal degeneration and segmental demyelination. Muscle biopsy specimen showed a marked predominance and hypertrophy of type-I fibres and atrophy, especially of type-II fibres.     

Excitability properties of motor axons in patients with spontaneous motor unit activity

OBJECTIVES: Measures of nerve excitability provide information about biophysical properties of peripheral axons in disease states. One measure, the strength duration time constant (tau(SD)), was previously reported to be prolonged in motor axons of patients with acquired neuromyotonia. The present study used a new protocol that applies a more comprehensive and sensitive panel of measures of axonal excitability, to determine firstly whether changes in tau(SD) were present in a group of patients with evidence of spontaneous motor unit activity; and secondly, if such changes in tau(SD) were present, whether other parameters of axonal excitability were affected, to clarify the mechanism of the change in tau(SD). METHODS: Eleven patients with both symptoms and EMG evidence of spontaneous motor unit activity were studied. Eight patients had autoimmune associated acquired neuromyotonia (aNMT) and three had the cramp fasciculation syndrome. The protocol first measured stimulus-response behaviour using two stimulus durations (from which the distribution of strength-duration time constants was estimated), and then threshold tracking was used to determine threshold electrotonus to 100 ms polarising currents, a current-threshold relation (indicating inward and outward rectification), and the recovery of excitability after supramaximal activation. RESULTS: The results were compared with previously published normal data. The value for tau(SD) of motor axons in the patient group was 0.43 (0. 02) ms (mean (SEM)), identical with the control value. Most other indices of axonal excitability, including those dependent on fast potassium channels, were also found to be normal. When compared with age matched controls however, the patients with acquired neuromyotonia had significantly greater late subexcitability after an impulse, greater excitability overshoots after depolarisation or hyperpolarisation, and more accommodation. CONCLUSIONS: No clear evidence for the mechanism of ectopic discharge in these patients was obtained, probably because the activity was generated focally, and most often at the motor nerve terminals. The unexpected finding of increased excitability overshoots and accommodation compared with age matched controls, suggests a relative up regulation of slow potassium conductance, possibly as a consequence of the continuous motor unit activity.     

Sensitivity of motor unit potential analysis in facioscapulohumeral muscular dystrophy

Template-operated motor unit potential (MUP) analysis has made quantitative electromyography (EMG) feasible, even in busy laboratories, but validation of this approach is still necessary. In the present study, the utility of multi-MUP analysis was assessed in patients with a molecular genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD). Manual assessment of muscle strength and concentric-needle EMG of the biceps brachii and vastus lateralis muscles were performed. The sensitivity for diagnosing myopathy (mean values and outliers) was tested for eight MUP parameters and four of their combinations. The group comprised 31 patients. Elbow flexion and knee extension strength was normal in 45% and 52% of patients, respectively. The most sensitive MUP parameter was thickness, followed by duration. A combination of three MUP parameters (thickness, amplitude, and duration/area) was needed for maximal sensitivity. The study demonstrated a high sensitivity of multi-MUP analysis in FSHD. Myopathic abnormalities were demonstrated in all weak biceps brachii muscles, and in 77% of biceps brachii muscles with normal strength.     

Continuous motor unit activity syndromes: a video-polysomnographic study.

OBJECTIVE: To ascertain the presence of abnormalities of sleep in patients with continuous motor unit activity with and without symptoms of central nervous system involvement. METHODS: Five patients with isolated neuromyotonia (Isaacs' syndrome) and 1 patient with Morvan syndrome underwent 24-h videopolysomnographic recording to investigate sleep structure, motor activities and autonomic variables during sleep. RESULTS: Macro- and microstructural organization of sleep and of the attending autonomic variables were substantially normal in patients with Isaacs' syndrome. On the contrary, sleep structure was severely disrupted with subcontinuous dream enactment and hallucinations in the patient with Morvan syndrome. The pattern of the neuromyotonic discharges, however, was not different between the patients with Isaacs' syndrome compared to Morvan syndrome, the EMG discharges persisting throughout the 24 h of recording and affecting wakefulness and sleep equally. CONCLUSIONS: Neuromyotonia is compatible with normal organization of sleep. The severe sleep abnormalities observed in Morvan syndrome cannot be simply attributed to the effects of neuromyotonia of peripheral origin. SIGNIFICANCE: Even though neuromyotonia is common to both Isaacs' and Morvan syndromes, the two conditions differ significantly in regard to CNS involvement with sleep abnormalities and lumping the two conditions together is not justified on clinical and neurophysiological grounds.     

The motor unit in muscular dystrophy, a single fibre EMG and scanning EMG study.

Dystrophic muscle shows increase in fibre density, abnormally low jitter in some recordings and more often increased jitter. The cross section of the motor unit has normal length. There are no signs of abnormal volume conduction characteristics. The increased fibre density is believed to be due to localised increase in the number of muscle action potential generators. The findings are compatible with a remodeling of the motor unit due to fibre loss and a reparative process with fibre regeneration and reinnervation.