Fasciculations and muscle twitching

Fasciculations are brief, irregular, spontaneous twitches of a group of muscle fibres belonging to one motor unit, seen under the skin as flickering without joint movement. Most are benign.

Anatomy and physiology. A motor unit is one anterior horn cell, its axon and the muscle fibres it supplies. Fasciculation follows spontaneous discharge anywhere along the lower motor neuron, from the cell body to the distal axon terminal.

Mechanisms. Hyperexcitability of the motor neuron or axon from channel dysfunction (benign), axonal degeneration and collateral sprouting (disease), metabolic and drug effects on membrane stability, and antibody mediated potassium channel dysfunction (neuromyotonia).

Classification. Benign fasciculation syndrome (isolated fasciculations with no weakness, wasting or reflex change), cramp fasciculation syndrome, peripheral nerve hyperexcitability syndromes (neuromyotonia, Isaacs syndrome), and fasciculations as a feature of lower motor neuron disease.

Key distinctions. Fasciculations with weakness, wasting, absent or brisk reflexes, bulbar symptoms or weight loss need urgent evaluation. Myokymia (continuous undulating, worm like movement, such as eyelid twitching) and myoclonus, tremor and tics are different phenomena.

History. Sites, duration, daily pattern, relation to exercise, caffeine, sleep deprivation, stress and recent febrile illness. Ask about cramps, stiffness, muscle weakness, wasting, difficulty climbing stairs, dropping objects, speech or swallowing difficulty, breathlessness lying flat, weight loss, sweating and anxiety. Ask about family history of motor neuron disease, spinal muscular atrophy or neuropathy.

Drug and toxin history. Salbutamol and other beta agonists, theophylline, caffeine, nicotine, amphetamines, corticosteroids, levothyroxine excess, anticholinesterases (neostigmine, pyridostigmine), diuretics and laxatives (electrolyte loss), proton pump inhibitors (hypomagnesaemia), lithium, amphotericin B, platinum agents, and suxamethonium exposure. Occupational exposure to organophosphate pesticides, lead and mercury.

Examination.

• Observe muscles at rest for 1 to 2 minutes in a warm room, in the tongue (rest in the mouth, not protruded), shoulders, thighs, calves and hands.
• Power in each muscle group, muscle bulk and wasting (first dorsal interosseous, thenar, tibialis anterior), tone, reflexes (brisk reflexes in a wasted limb suggest motor neuron disease), plantar responses, jaw jerk, tongue wasting and fasciculation, palatal movement, speech, and cough.
• Sensation and distribution of any deficit, signs of radiculopathy, myelopathy or neuropathy.
• General: pulse, thyroid, sweating, tremor, weight, forced vital capacity.

Red flags

• Weakness, wasting or reduced exercise tolerance in the same area
• Bulbar symptoms (slurred speech, swallowing difficulty, tongue fasciculation with wasting) or weight loss
• Combination of lower motor neuron signs with brisk reflexes or extensor plantars
• Breathlessness lying flat, morning headache, or forced vital capacity under 80 percent of predicted
• Progressive spread to new regions
• Fasciculations after organophosphate exposure with salivation, sweating, miosis and bradycardia

Special groups. Young men with proximal weakness, gynaecomastia and tremor: X linked spinal bulbar muscular atrophy. Older adults: radiculopathy and motor neuron disease become more likely. Region specific: poliomyelitis sequelae and organophosphate exposure.

Benign

• Benign fasciculation syndrome, cramp fasciculation syndrome
• Exercise, caffeine, nicotine, anxiety, sleep deprivation, fever and viral illness

Lower motor neuron and motor neuron disease

• Amyotrophic lateral sclerosis (motor neuron disease), progressive muscular atrophy, progressive bulbar palsy
• Spinal muscular atrophy, X linked spinal bulbar muscular atrophy (Kennedy disease)
• Post-polio syndrome, monomelic amyotrophy
• Multifocal motor neuropathy with conduction block, chronic inflammatory demyelinating polyneuropathy
• Hereditary motor and sensory neuropathy

Radiculopathy and structural

• Cervical or lumbar radiculopathy, cervical spondylotic myelopathy
• Syringomyelia, spinal tumour, root compression
• Lumbar canal stenosis

Metabolic and endocrine

• Hypomagnesaemia, hypocalcaemia, hypokalaemia, hyperkalaemia, hyponatraemia
• Thyrotoxicosis, hyperparathyroidism
• Uraemia, vitamin B12 deficiency

Drugs and toxins

• Beta agonists, caffeine, theophylline, anticholinesterases, corticosteroids, levothyroxine excess, suxamethonium
• Organophosphate and carbamate poisoning, lead and mercury toxicity

Nerve hyperexcitability

• Neuromyotonia (Isaacs syndrome), Morvan syndrome, anti-CASPR2 and anti-LGI1 associated disease, thymoma
• Myotonic dystrophy and myotonia congenita (myotonia mimics twitching)
• Tetany from hypocalcaemia or alkalosis

Mimics

• Myokymia, myoclonus, tremor, tics, focal motor seizures, muscle cramps
• Muscle disease with myopathic twitching, rippling muscle disease

Reasoning. Examine for weakness, wasting and reflex changes. When there are no signs, test for reversible causes, reassure and review. When signs of lower motor neuron or upper motor neuron involvement are present, proceed to neurophysiology and imaging urgently.

First line. Full blood count, urea, electrolytes, creatinine, calcium, magnesium, phosphate, glucose, liver function, thyroid stimulating hormone and free thyroxine, vitamin B12, ESR and C reactive protein, HIV and syphilis serology.

Also check creatine kinase. Mild elevation, up to 2 to 3 times the upper limit, occurs in motor neuron disease and exercise.

Neurophysiology. Nerve conduction studies and needle electromyography are the central investigation.

They show active denervation (fibrillation potentials, positive sharp waves), chronic reinnervation (large long duration motor units), and fasciculation potentials, and they identify conduction block (multifocal motor neuropathy) and neuromyotonic discharges.

Fasciculation potentials with normal strength, normal bulk and a normal rest of the EMG indicate a benign process. The yield is limited in the first weeks of disease, so repeat after 3 to 6 months if symptoms progress.

Further tests

• MRI cervical spine and brain for myelopathy, radiculopathy, syringomyelia and corticospinal tract changes.
• Anti-GM1 antibodies in suspected multifocal motor neuropathy.
• Anti-CASPR2, anti-LGI1 and voltage gated potassium channel complex antibodies for neuromyotonia, with chest CT for thymoma.
• Androgen receptor gene (CAG repeat) for suspected Kennedy disease; SMN1 gene testing for spinal muscular atrophy; SOD1, C9orf72 and other genes in familial motor neuron disease after counselling.
• Serum protein electrophoresis, CSF analysis, and lumbar puncture when inflammatory neuropathy is suspected.
• Forced vital capacity (sitting and lying), sniff nasal inspiratory pressure and nocturnal oximetry in motor neuron disease.
• Acetylcholinesterase activity (red cell) in suspected organophosphate exposure.

Diagnostic criteria for motor neuron disease. Progressive motor impairment with upper and lower motor neuron dysfunction in at least one body region, or lower motor neuron dysfunction in at least two regions, with electromyography support and exclusion of mimics. Fasciculations alone do not establish the diagnosis.

Limitations. Benign fasciculation can persist for years and anxiety may persist after reassurance. Early motor neuron disease may show a normal EMG. Normal MRI does not exclude motor neuron disease.

Benign fasciculation syndrome. Clear explanation that the movements do not predict motor neuron disease when strength, bulk, reflexes and EMG are normal. Stop caffeine, nicotine and stimulants, regularise sleep and treat anxiety. Review at 3 months, or earlier with new weakness. Avoid repeated testing without new signs.

Correct reversible causes

• Hypomagnesaemia: magnesium sulphate 2 g (8 mmol) IV over 15 minutes for severe or symptomatic deficiency (magnesium under 0.4 mmol/L), then 4 to 6 g over 24 hours.
• Reduce the magnesium dose in renal impairment, and monitor reflexes, respiratory rate and creatinine.
• Oral magnesium (magnesium glycerophosphate 4 mmol orally two to three times daily, or equivalent) for mild deficiency. Replace potassium and calcium together, and stop or change the causative proton pump inhibitor or diuretic.
• Hypocalcaemia with tetany: calcium gluconate 10 percent 10 mL IV over 10 minutes with ECG monitoring, repeated if needed, then an infusion.
• Hypokalaemia: potassium chloride orally 40 to 80 mmol daily in divided doses; IV at no more than 10 mmol/hour peripherally (up to 20 mmol/hour centrally with ECG monitoring).
• Thyrotoxicosis: propranolol 40 mg orally three or four times daily for symptoms (maximum 240 mg daily), with specialist antithyroid treatment.
• Vitamin B12 deficiency with neurological signs: hydroxocobalamin 1 mg IM on alternate days until no further improvement (up to 3 weeks), then 1 mg every 2 months.
• Drug effects: reduce or stop caffeine, beta agonist and other culprit drugs when safe.

Organophosphate or carbamate poisoning. Remove contaminated clothing and wash the skin, give oxygen, and give atropine 1 to 2 mg IV doubled every 5 minutes until secretions dry, heart rate is over 80 beats/minute and the chest is clear. Then run an infusion at 10 to 20 percent of the loading dose each hour.

Add pralidoxime 30 mg/kg IV over 30 minutes then 8 mg/kg/hour for organophosphates, with benzodiazepines (diazepam 5 to 10 mg IV) for seizures. Intensive care and poisons service advice.

Amyotrophic lateral sclerosis. Specialist multidisciplinary care.

• Riluzole 50 mg orally twice daily, taken 1 hour before or 2 hours after food. Check liver function monthly for the first 3 months, every 3 months for the rest of the first year, then periodically.
• Stop riluzole if ALT is over 5 times the upper limit or if neutropenia develops. It is contraindicated in significant hepatic impairment and in pregnancy. Evidence supports a survival gain of a few months.
• Edaravone IV 60 mg over 60 minutes daily for 14 days, then 14 days off, then cycles of 10 doses over 14 days followed by 14 days off, in selected early patients through specialist centres.
• Non-invasive ventilation when forced vital capacity falls under 50 percent, sniff pressure under 40 cmH2O, orthopnoea or nocturnal hypoventilation develops.
• Gastrostomy discussion when weight loss exceeds 10 percent or swallowing is unsafe.
• Sialorrhoea: glycopyrronium 1 mg orally two or three times daily, or hyoscine patches or botulinum toxin to salivary glands.
• Cramps and spasticity: baclofen 5 mg orally three times daily increased to a maximum of 100 mg daily; quinine is not used because of toxicity.
• Palliative care, communication aids, advance care planning and carer support from diagnosis.

Other lower motor neuron diseases. Multifocal motor neuropathy: intravenous immunoglobulin 2 g/kg over 2 to 5 days, repeated at intervals set by specialists; corticosteroids and plasma exchange are not effective. Inflammatory neuropathy: intravenous immunoglobulin or corticosteroids by specialist decision. Kennedy disease: supportive care; testosterone is avoided. Spinal muscular atrophy: specialist therapy.

Neuromyotonia and cramp fasciculation syndrome. Carbamazepine 100 mg orally twice daily, increased by 100 to 200 mg every 1 to 2 weeks to a usual 400 to 1,200 mg daily (maximum 1.6 g daily).

Monitor sodium, blood count and liver function on carbamazepine. Check HLA-B*1502 in people of Han Chinese, Thai or other South East Asian ancestry. An alternative is phenytoin 100 mg orally three times daily with levels.

Autoimmune neuromyotonia: intravenous immunoglobulin 0.4 g/kg daily for 5 days or plasma exchange, and thymectomy for thymoma.

Monitoring. Strength, bulk, reflexes and weight at each review; forced vital capacity every 3 months in motor neuron disease; liver function and blood count on riluzole and carbamazepine; electrolytes after replacement.

Referral and escalation. Urgent neurology within 2 weeks for any fasciculations with weakness, wasting or bulbar symptoms. Same day for respiratory compromise or organophosphate exposure. Endocrinology for thyroid disease; spinal surgery for compressive myelopathy.

Admission criteria. Respiratory compromise, bulbar failure with aspiration, poisoning, severe electrolyte disturbance with arrhythmia, or rapid progression needing urgent investigation.

Discharge and safety netting. Return for new weakness, wasting, difficulty swallowing or speaking, breathlessness lying flat, or fasciculations spreading. Benign cases need review at 3 months.