All myokymias whether focal (facial myokymia, FM), or myokymia circumscribed to the eyelid (eyelid myokymia, EM) are hyperexcitability disorders of the motor unit caused by excessive involuntary myokymic discharges of the facial nerve.¹¹ It is hypothesized that EM is generally considered a forme fruste of FM, which in turn is considered a forme fruste of neuromyotonia; the difference lies in the frequency of myotonic discharges and the extent and severity of muscle involvement.³,¹¹,¹²

The exact cause of EM is not clear, but the condition is usually considered benign, and an etiologic cause is rarely found. An insight into the etiopathogenesis of EM can be provided by a closer look at the pathogenesis and etiology of its more ominous counterpart, FM, which is a focal form of myokymia circumscribed to the facial nerve. The latter condition is characterized by extensive muscle involvement and involuntary muscle fiber activity in one-half of the face associated with distinctive electromyographic myokymic discharges.²,¹¹,¹³ FM is hypothesized to develop due to an unstable axon membrane acting as an ectopic generator of discharges, and it is typically associated with a lesion within or near the ipsilateral pontine tegmentum (dorsal pons) where the motor nucleus of the facial nerve is located.¹⁰ Alternatively, other lesions in the vicinity of the facial motor nucleus (supranuclear, perinuclear, or infranuclear lesions) may also cause facial nerve hyperexcitability.¹⁰,¹⁴ The underlying pathophysiology of EM is probably identical, and it may be safe to assume that in EM the underlying pathogenetic mechanism appears to be hyperexcitability of the peripheral motor nerve axons of the facial nerve.¹,²,³ The relatively chronic, localized, nonprogressive nature of EM, which rarely involves other facial muscles, probably corroborates this hypothesis²; however, it is not entirely implausible that a more central mechanism causing deafferentation of inhibitory pathways, and ultimately resulting in localized hyperexcitability of the orbicularis muscle, is responsible for EM.¹¹

The list of confirmed causes of EM is short. In chronic cases, It may rarely be indicative of an underlying neurological disease like multiple sclerosis.³,¹⁰ EM has also been described in association with the use of an antiepileptic drug called topiramate, which has a variety of clinical applications including prophylaxis against migraine and binge eating.¹⁵ EM was also reported in patients with leprosy and in patients subjected to an experimental noninvasive brain stimulation technique called anodal transcranial direct current stimulation, which has recently shown promise in the management of chronic pain, depression, and a variety of other conditions.¹⁶,¹⁷ A recent systematic review has suggested that high cannabis consumption may lead to myokymia. Although a tetrahydrocannabinol (THC) serum level of more than 1 µg/L was associated with eyelid tremors in 86% of patients in one study, other studies showed different results.⁴

On the other hand, the list of underlying causes of FM is extensive. The most common causes include multiple sclerosis, pontine glioma, and Guillain-Barré syndrome.²,³ Other brainstem neoplasms (cerebellar astrocytoma, metastatic tumors, or acoustic neuroma) and infections (tuberculosis and cysticercosis) may also cause FM.²,³,¹¹,¹⁴ Rarer causes of FM may be genetic (hereditary channelopathy caused by a mutation in one of the voltage-gated potassium channel genes, KCNA1, and less commonly KCNQ2), autoimmune (antibodies to voltage-gated potassium channels [VGKCs]), toxic (rattlesnake venom), or drug-induced (flunarizine, clozapine, or gold salts).¹²,¹³,¹⁵,¹⁸ Autoimmune voltage-gated potassium channelopathies are associated with a wide spectrum of peripheral as well as central hyperexcitability disorders.¹²,¹⁸,¹⁹ To the best of our knowledge, this disorder has not been demonstrated in association with isolated EM,²⁰ and neither have most of the above-listed causes of FM with the exception of multiple sclerosis.³,¹⁰ Of note is that anti-IgLON5 disease, a recently described neurological disease entity that develops due to an antibody-mediated disruption of IgLON5 (a curious cell adhesion protein of uncertain function), is frequently associated with FM.²¹ Anti-IgLON5 disease possesses dual features of autoimmunity and neurodegeneration and manifests clinically with bulbar dysfunction (dysphagia, dysarthria, vocal cord palsy, and/or respiratory difficulties), gait difficulties, and sleep alterations in addition to hyperkinetic movements (myoclonus, myorhythmia, myokymia, etc.).²¹