Ocular neuromyotonia

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 by Bayan Al Othman, MD on June 30, 2020.


Disease

Ocular neuromyotonia (ONM) is a rare ocular motor disorder characterized by intermittent, tonic spasms of one or more of the extraocular muscles, resulting in strabismus and paroxysmal diplopia [1]. Episodes of ONM are caused by involuntary neural discharges and delayed muscle relaxation due to a damaged nerve [1][2].

Etiology

ONM commonly occurs with the history of cranial radiation, nerve compression of vascular or meningeal origin, and autoimmune disorders (e.g. myasthenia gravis and thyroid disease) [3][4].

The tumors that could be associated with ONM of the ocular motor nerves include parasellar or sellar region masses after radiotherapy [5][6][7][8]. The interval between the clinical presentations of ONM and radiotherapy can range from 2 months to 18 years [1].

Other rare causes of ONM include concomitant chemotherapeutic agents use (e.g. cisplatin, fluorouracil) during radiation therapy, vitamin B12 or D deficiency, myelography with thorium dioxide, brainstem demyelination, botulinum toxin injection, and a neurocognitive disorder, alcohol, and cataract surgery [1][9][10][11][12].

Pathophysiology

The pathophysiology of ONM is not entirely established [13]. ONM is believed to be due to the damage to the myelin sheath of the nerve and most commonly affect the oculomotor nerve or the abducens nerve [5].

Segmental cranial nerve demyelination from radiogenic damage, compressive disorders, microvasculopathy, or other conditions leads to ephaptic transmission (or crosstalk) between local neurons [1][13][14]. This transmission of nerve impulses along lateral contact of demyelinated nerves and independent of synapse could explain the hyperactivity, prolongation, and repetition of tonic contractions of ONM [5][13][14].

In addition, Eggenberger suggests that two types of aberrant function, reflection and sprouting axons, may create a “reflecting nerve circuit” and amplify the inverted signal [15].

Other plausible mechanisms of ONM include axonal hyperexcitability due to dysfunction of potassium channels in the neuronal cell membrane, denervation that leads to changes in neural transmission, and central neural disorganization by retrograde degeneration and reorganization of patterns of motor output in the nuclei [1][16].

Thyroid-associated orbitopathy may lead to ONM due to inflammatory changes and crowding of the oculomotor nerves and muscle cells [1]. Inflammatory cell infiltration and mucopolysaccharide deposition in the interstitial spaces of the endomysium may cause neuronal excitability and axonal degeneration [1][2]. During the autoimmune process of Graves’ orbitopathy, thyroid peroxidase antibodies may initiate an inflammatory cytokine release in the muscles and lead to direct demyelination [1][16].

Primary prevention

As vitamin B12 is crucial for the maintenance and development of myelination, vitamin B12 may prevent changes in the myelin sheath and poor neural conduction [1].

Diagnosis

History and Physical examination

The clinical presentations of ONM are transient diplopia and strabismus that occur spontaneously or after an eccentric gaze due to a tonic contraction or spasms of the extraocular muscles [1]. These episodes can last from a few seconds to several minutes, but may not be reproduced during the examination [12].

Most cases are unilateral and primarily occur in adults [5]. Patients may have an otherwise normal ophthalmological, fundoscopic, and biomicroscopy examinations [1].

A detailed history can be crucial in elucidating the cause of ONM. In the absence of a history of irradiation, a neurological examination and neuroimaging, with special attention to the posterior fossa, are recommended [1][17]. Electromyography, electrooculography, videotaping of the eye movements, and biopsy of the muscle can further analyze ocular motor spasms [16].

Clinical diagnosis

ONM can be a clinical diagnosis with a good attention to the medical history and thorough ocular motility examinations by observing the eyes in the primary position and after several seconds of eccentric gaze [1]. The eye may get stuck after looking in the direction of the affected muscle, inducing spasms or sustained diplopia on looking back to the primary position [3]. Prolonged periods of eccentric gaze are better to be tested to not miss the diagnosis [1].

Laboratory test

Standard thyroid function testing is recommended to be performed to rule out possible thyroid dysfunction [1].

Imaging

MRI scans of the brain can be performed to the patients with possible ONM to exclude secondary causes [3].

Differential diagnosis [1][14]

• Superior oblique myokymia

• Cyclic paralysis of the oculomotor nerve

• Convergence spasm

• Ocular myasthenia gravis

• Early stages of Graves disease

• Decompensated phoria

Management

Medical therapy

The standard pharmacological treatments for ONM are membrane stabilizing agents, including carbamazepine, gabapentin, phenytoin, and lacosamide [1][3].

Carbamazepine, the treatment of choice, may decrease the ephaptic transmission by interacting with different receptors and channels on the neuronal membrane and reducing the frequency of prolonged, repetitive firing of action potentials [1][18].

Undesirable side effects of carbamazepine may limit the treatment in some cases [1]. The adverse effects include allergic reactions, GI side effects, dizziness, fatigue, and drowsiness. Rare side effects include diplopia, nystagmus, hallucinations, ataxia, leukopenia, thrombocytopenia, hyponatremia, and impaired liver function [1].

Carbamazepine may be contraindicated if patients have atrioventricular block, porphyria, bone marrow depression, or the uses of alcohol, muscle relaxants, diuretics, lithium, enzyme inhibitors, or MAO inhibitors [1].

Lacosamide has shown some success in patients who experience adverse reactions to carbamazepine [3]. Compared to carbamazepine, lacosamide has a lower risk of cross-reactivity and fewer side effects [3][19].

ONM presentations may disappear after oral or intramuscular vitamin supplementation of B12 and D if ONM is induced by hypovitaminosis [1].

It is important to check liver and renal functions and a complete blood count at treatment initiation and at the 6-week follow-up [1].

Surgery

If refractory to medical treatments, surgical microvascular decompression may be helpful [3][20]. Also, binocular fusion with strabismus surgery can relieve ONM of a paretic rectus muscle [21].

Prognosis

The prognosis of ONM depends on the underlying cause and its complications. Spontaneous resolution of ONM may occur as well [1].

Additional Resources

Ocular neuromyotonia: https://www.youtube.com/watch?v=0NAb70xWZjQ

References

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