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Neuromyotonia is a syndrome characterised by motor unit hyperactivity leading to muscle cramps, fasciculations, muscle stiffness, and persistent muscle contraction. In most neuromyotonia patients, the disorder is acquired. An autoimmune or paraneoplastic origin is common.1–3 Myasthenia gravis, thyrotoxicosis, systemic sclerosis, inflammatory demyelinating neuropathies, thymoma, bronchial carcinoma, and small cell lung cancer may be associated. Here, we report a patient with neuromyotonia, associated with myasthenia gravis and anti-voltage-gated potassium channels (VGKC) and anti-acetylcholine receptor (AChR) antibodies without thymoma.
A 58 year old man of Portuguese descent presented at our neuromuscular clinic with dysesthesia and hypesthesia in the first three fingers of the right hand. Symptoms had started nine years before and had been attributed to cervical radiculopathy. Over the years, the symptoms had been fluctuating but for the past two months they had become debilitating. Therefore, the patient sought a second opinion. The patient volunteered that, although right hand pain was his main complaint, for many years his hands and feet were swollen and red. There was stiffness and loss of dexterity of all fingers. He had difficulty writing, using scissors, and using a handheld computer. Frequent cramps occurred in the fingers and toes. There was painful tension in the calfs, the feet, and the hands. The patient also complained of excessive sweating. These symptoms had progressively worsened. One year before presenting to us, he developed ptosis of the right upper eyelid, rapidly followed by vertical and horizontal diplopia. These symptoms were fluctuating with worsening in the evening. Repetitive stimulation of the facial nerve showed a decremental response, symptoms and signs disappeared after injection of prostigmine, and anti-AChR antibodies were found. It was concluded that the patient had ocular myasthenia and the patient was treated with oral methylprednisolone. Improvement was rapid and after a few weeks treatment was stopped. Two weeks before presentation, the patient again complained of right palpebral ptosis and diplopia. The symptoms were responsive to pyridostigmine bromide. The medical history was remarkable for ophthalmical migraine, arterial hypertension, and hypercholesterolaemia. Treatment consisted of fenofibrate and metoprolol. The family history was non-contributory.
On clinical examination, continuous undulating movements were noted in the small muscles of hands and feet and in the orbicularis oculi muscles. Small amplitude, involuntary movements of fingers and toes were conspicuous at rest. The fingers were stiff and the patient had difficulty performing rapid alternating movements with his fingers. Tactile and pain sensation was diminished only in the first three fingers of the right hand. Tinel's and Phalen's signs were present at the right wrist and there was right hand grip weakness. Right upper eyelid ptosis, rapidly increasing on upward gaze was noted. Horizontal diplopia occurred in right lateral and vertical gaze directions. Deep tendon reflexes were normal and plantar responses were flexor.
Complete blood count, serum creatinine, blood urea nitrogen, liver function tests, serum electrolytes, thyroid function tests, and serum creatine kinase were normal. Rheumatoid factor was negative and there were no antibodies against striated muscle, but antinuclear antibodies were positive at a titre of 1/80. Prostate specific and carcinoembryonic antigens were negative. Both AChR antibodies (26 nmol/ml, normal values less than 0.5 nmol/ml) and VGKC antibodies (1091 pmol/l (normal values less than 100 pmol/l) were detected. Computed tomography of the chest was normal.
Nerve conduction studies showed evidence of a severe rightsided carpal tunnel syndrome, but otherwise they were normal. Needle electromyography revealed myokymic discharges in distal muscles of upper and lower extremities (fig 1). These discharges consisted of bursts of motor unit potentials, appearing as doublets, triplets, or multiplets with intraburst frequencies of 40 to 100 Hz. Burst recurrence was irregular with an interburst frequency of 5–8 Hz. There was evidence of mild chronic denervation with slightly reduced recruitment in distal muscles.
Anti-VGKC antibodies are found in approximately 40% of patients with acquired neuromyotonia2–4; they are also found in patients with other neuromuscular hyperexcitability syndromes, such as cramp fasciculation syndrome, acquired rippling muscle syndrome, facial myokymia.5,6 In a significant proportion of these patients, coexistence of myasthenia gravis and neoplastic disorders, thymoma in particular, is observed.4,5 About 20% of all reported neuromyotonia patients had thymoma; 70% thereof also had myasthenia gravis and anti-AChR antibodies and 20% had anti-AChR antibodies without overt myasthenia gravis. The absence of anti-striated muscle antibodies and of radiological evidence of mediastinal tumour in a patient with neuromyotonia of nine years duration illustrates that the association of autoimmune neuromyotonia and myasthenia gravis can occur without thymoma.
Conflicts of interest: The University of Oxford on behalf of AV receives consulting fees from RSR Ltd who market AchR antibody assays