What is myokymia

Myokymia is characterized by spontaneous, fine fascicular contractions of muscle without muscular atrophy or weakness. The clinical phenomenon is characterized by its classic quivering movement of the involved muscle without movement of the joint ¹. Myokymia can be seen in muscles innervated by cranial or spinal nerves. The distribution can be either regional or generalized, depending on the etiology. Also, it can be seen transiently in healthy subjects after strenuous exercise.

Although myokymia can be seen in patients with different neurological and medical conditions and occasionally even in healthy subjects, it is a relatively rare clinical manifestation ¹.

Most of the diseases associated with myokymia are not life threatening.

The prognosis is solely dependent upon the underlying etiologies. Myokymia is reversible with successful treatment of the cause. ².

Myokymia is considered benign when detected in patients after strenuous exercise.

The exact mechanism(s) of myokymia is not well understood ¹. Myokymia of the facial muscles is believed to originate from the facial nucleus or from some contribution by a supranucleus process; however, the presence of myokymia in polyradiculopathy indicates the possibility of a more distal generator. Most authors agree that myokymia in other parts of the body is generated by distal motor axons, either by a primarily axonal process or by segmental demyelination with secondary axonal dysfunction. Some have postulated that transaxonal ephaptic excitation occurs peripherally after focal nerve damage leads to formation of an artificial synapse.

Myokymia is believed to be associated with generation of spontaneous activity, including myokymialike discharge in the dystrophic mouse whose nerve root axons have no Schwann-cell enwrapment. By this mechanism, spontaneous discharge could initiate volleys of activity or afferent fibers could directly stimulate efferent fibers in the vicinity of the lesion and produce a self-perpetuating reverberating circuit.

The central nervous system’s electrotonic spread of discharge from rhythmic generators toward anterior horn cells also might play a role in generation of the spontaneous discharge. Each patient may have a different operating mechanism, depending on the particular areas involved and the different etiologies. The fact that patients with Isaacs syndrome respond dramatically to treatment of myokymia with phenytoin and/or carbamazepine ³ suggests a possible abnormality of the potassium channel in this particular entity.

Myokymia symptoms

Patients with myokymia may present with symptoms of pain, cramps, spasms, weakness, stiffness, or twitching.

Sensory symptoms are reported rarely, unless the underlying etiology(ies) includes sensory nerve involvement.

Typical myokymic discharges also can be seen in the electromyography (EMG) studies of patients referred for totally unrelated complaints.

Facial myokymia

Affected muscles show slow, undulating, fine movements on the surface of the skin due to activation of the most superficial muscle layers. Facial weakness can be present in the involved muscles.

Electromyography (EMG) study shows typical myokymic discharges of spontaneous, rhythmic/semirhythmic bursts of normal-appearing potentials of 30-60 Hz. The bursts of each group of potentials are followed by a period of silence, with subsequent repetition of grouped discharges of identical potentials. The spontaneous activities are not altered by voluntary activation of the muscles.

Focal or segmental myokymia

These types of myokymia commonly are seen in the limbs or particular segmental level(s). Physical findings mostly are related to the underlying etiology(ies), which is usually asymptomatic and not a major concern of the patient.

Electromyography (EMG) study shows myokymic discharges similar to those recorded in facial myokymia.

Generalized myokymia

A triad of myokymia, muscular stiffness, and decreased deep tendon reflexes was first described by Isaacs in 1961; it also is called Isaacs syndrome ⁴.

1. Muscle weakness and atrophy and excessive sweating are frequently associated features. Smooth muscles and cardiac muscles typically are spared.
2. Sensory symptoms are rarely present.
3. The muscular stiffness is different than that seen in myotonia, both clinically and electrodiagnostically. Although both can be exacerbated by cold, myokymia can be detected when the muscle is at rest and during sleep. Patients with myotonia are normal at rest; the stiffness is induced by mechanical stimulation.

The myotonic discharge recorded by electromyography (EMG) ceases upon relaxation of the muscle, while spontaneous grouped discharges of myokymia persist for some time, well above the abnormal pattern that was present before the voluntary contraction.

The EMG features encountered in patients with generalized myokymia include the previously described typical myokymic discharge or neuromyotonia, which has a much higher frequency of discharges (up to 300 Hz).

Generalized myokymia in other clinical entities shares less consistent clinical manifestations.

Myokymia causes

Facial myokymia

This type of myokymia is seen more commonly than other types.

Facial myokymia has been reported to be associated with inflammatory demyelinating diseases, brainstem neoplasms, Guillain-Barré syndrome, or other intramedullary pontine lesions. Facial myokymia also has been reported in patients with history of radiotherapy, with findings similar to those of more common brachial or lumbar radiation plexopathies.

Focal or segmental myokymia

The majority of patients with a history of radiation therapy have myokymic discharges detected within the field of radiation. Metastatic lesions generally are believed to be less likely to generate myokymia. The amount of radiation ranges widely, though myokymia rarely is reported with radiation doses less than 10 gray (Gy).

Electrodiagnostic findings are usually consistent with plexopathy. Other less common causes include acute or chronic inflammatory polyradiculoneuropathy ⁵ (with or without coexistent systemic vasculitis), ischemic or traumatic focal neuropathy, entrapment neuropathy, polyradiculopathy secondary to torticollis, syringomyelia, and chronic idiopathic plexopathy.

Transient myokymia, described in the calf or hand muscles, was reported after brief strenuous exercise, hypokalemia, hypomagnesemia, and increased caffeine intake. It usually resolves spontaneously over weeks to months.

Isaacs syndrome

Generalized myokymia is one of the cardinal features of Isaacs syndrome, which is a rare clinical entity with no known common etiologies. Congenital and acquired forms are described.

The acquired form has been associated with neoplasms, thymoma, myasthenia gravis, lymphomas, and a variety of autoimmune nervous system disorders.

Spinal anesthesia and peripheral nerve block fail to abolish the myokymic discharges. Blocking the motor end plate transiently terminates the spontaneous activities. Evidence from muscle and nerve biopsies also favors a neurogenic origin.

Generalized myokymia also can be seen in patients with systemic illnesses (eg, thyrotoxicosis, uremia) and following binge consumption of alcohol, exposure to toxins, timber rattlesnake bite, gold therapy, and penicillamine therapy.

One case of myokymia as an initial and predominant manifestation of dermatomyositis has been reported.

Myokymia diagnosis

Complete blood count, chemistry, creatine kinase, thyroid testing group, sedimentation rate, Lyme titer, Venereal Disease Research Laboratory (VDRL) test, and rheumatology screening are the basic laboratory tests for all patients with clinical myokymia. Serum alcohol level and toxic screen are recommended for acute onset of generalized myokymia.

Imaging studies

Neuroimaging studies with CT scan or MRI usually are performed for certain regions after careful examination and in cases in which electrodiagnostic studies have localized a lesion to a particular area. For example, if facial myokymia is confirmed, MRI study of the brain with special attention to posterior fossa is ordered to search for an anatomic lesion. Imaging studies are not otherwise necessary for establishing the diagnosis of myokymia.

Other tests

Nerve conduction velocity (NCV) and EMG studies are necessary to qualify and quantify neurogenic/myogenic dysfunction.

• Nerve conduction velocity (NCV) can detect the presence of plexopathy, mononeuropathy, and polyneuropathy (axonal or demyelinating).
• EMG can confirm the presence of myokymic discharges or neuromyotonia. The specific findings of myokymia in EMG examination are detailed in the Physical section.
• EMG study also can document the presence of neurogenic/myogenic dysfunction and its distribution.
• Information obtained through these studies serves as a guide for further diagnostic investigation. Serial studies can objectively document the evolution of the myokymia.

Procedures

Lumbar puncture with examination of cerebrospinal fluid (CSF) usually is performed for patients with documented acute or chronic polyradiculoneuropathy, central nervous system demyelinating disorder, or other suspected inflammatory, infectious, or neoplastic processes.

Myokymia treatment

Treatment of myokymia is focused largely on the underlying etiology. Most patients with facial or focal limb myokymia are not particularly disturbed by the myokymia itself. The accompanying symptoms of the particular neurological or medical conditions are the major concern to patients and their caretakers.

• For conditions secondary to thyrotoxicosis, poisoning, and alcoholic cramp syndrome, the myokymia disappears with resolution or improvement of the medical conditions.
• Patients with radiation plexopathy require no intervention.
• Myokymia seen in acute or chronic polyradiculoneuropathy usually improves with immunomodulatory therapy.
• Transient myokymia that develops after strenuous exercise resolves spontaneously over weeks to months.
• For patients with stiffness and painful cramps, conditioning of muscles by range of motion and isometric exercise is helpful.

Medications

Phenytoin and carbamazepine have been proven to be effective in treating patients with generalized myokymia, specifically patients with continuous muscle fiber activity described by Isaacs syndrome. High therapeutic drug levels usually are required to reach satisfactory control of symptoms. EMG can objectively document the disappearance of myokymic discharges.

Other newer-generation anticonvulsant medications with mechanisms of action modulating sodium and potassium channels can also be tried with caution. Monitoring of potential adverse effects of phenytoin and carbamazepine and precautions for these drugs are no different from when they are used to treat epilepsy. Medications such as benzodiazepines have been tried with no consistent benefit.

Myokymia vs Fasciculations

Fasciculations are visible, fine and fast, spontaneous and intermittent contractions of fine muscle fibers ⁶. Some neurologists call them verminosis, because they look like worms moving below the dermis ⁷.

In 1963, Reed and Kurland warned that the presence of fasciculations was not necessarily a prelude to the onset of a progressive and lethal disease, due to the involvement of the lower motor neuron ⁸. Since then, several authors have explored this topic, defining a benign fasciculation syndrome (BFS), that most frequently affects young healthcare professionals ⁹, who, in some cases, have already developed dyspnea.11 An interesting Australian prospective study published recently examined the cases of 20 physicians (20 consecutive cases) complaining of fasciculations ⁹. Fourteen of them were very concerned about being diagnosed with ALS. The fasciculations were mainly in the lower limbs, which had normal muscle strength. In the electrophysiological study, fasciculations potentials were of the simple type, motor conduction was normal and no signs of denervation or neurogenic changes of motor units were apparent.

These authors, in agreement with others, concluded that physical exercise, stress, fatigue and caffeine abuse can precipitate or aggravate this picture. Among the other six individuals in the sample, five patients manifested a cramp-fasciculation syndrome (Denny-Brown syndrome) and only one suffered from amyotrophic lateral sclerosis (ALS).

Some authors have stated that, in order to establish the clinical diagnosis of benign fasciculation syndrome (BFS), a minimum of five years is necessary, due to the evolution, in some cases, of the motor neuron disease ¹⁰.

A work by Fermont et al. ¹¹ reported the prevalence and distribution of fasciculations in healthy adults. The potentials were studied by ultrasound in 58 individuals from different age groups. The subjects were also interviewed using questionnaires about the exacerbation of caffeine consumption and physical activity. Of the total sample, 43% had fasciculations, especially in the hallucis longus abductor muscle. In the lower limbs, fasciculations were rarely found and reported. Older individuals showed more fasciculations than young adults. The authors have noted that certain physical activities, when very intense, may exacerbate symptoms in the lower limbs.

It is noteworthy that there is no specific treatment for fasciculations, as it is symptomatic ⁶. The use of antiepileptic drugs such as carbamazepine and phenytoin has shown a partial therapeutic response. Gabapentin can also be used generally at low doses from 300 to 600 mg ⁷. However, due to their benign and transitional nature, it is not always necessary to treat fasciculations. A recent study proposed a new approach to treat the Cramps Syndrome and Benign Fasciculations through the identification and correction of sleep apnea, which in most cases can be one of the triggers ¹².

Myokymia vs Blepharospasm

Benign essential blepharospasm starts out as increased blinking of both eyes and may progress to the eyelids being squeezed shut. This type of eye twitching is relatively uncommon but can be extremely severe, affecting all aspects of life.

Eyelid myokymia

Eyelid myokymia or eyelid twitching affects only the eyelid. This type of twitch or spasm is very common and happens to most people at one time or another. Myokymia can involve either the upper or lower eyelid, but usually only one eye at a time. Myokymia can range from barely noticeable to bothersome. The twitching usually goes away within a short time but may recur over a few hours, days or longer. Prognosis is excellent in most cases.

A history of stress, fatigue, and excessive caffeine or alcohol intake may be present. The use of topiramate in migraine sufferers has been questioned as a cause of eyelid myokymia ¹³.

If the eyelid myokymia is associated with contraction of other parts of the face, hemifacial spasm, blepharospasm, Meige syndrome, and spastic-paretic facial contracture should be excluded. Activation of the facial muscles (eg, big smile, eyelids squeezed shut) helps to determine if the eyelid myokymia is associated with contractions of other parts of the face.

In most cases, eyelid myokymia is benign, self-limited, and not associated with any disease. Intervention is usually unnecessary. Rarely, eyelid myokymia may occur as a precursor of hemifacial spasm, blepharospasm, Meige syndrome, spastic-paretic facial contracture, and multiple sclerosis ¹⁴.

The incidence and prevalence of eyelid myokymia are unknown, but symptoms of eyelid myokymia are frequently encountered in the ophthalmic clinic.

Eyelid myokymia causes

The cause of eyelid myokymia is unknown but may be associated with stress, fatigue, and excessive caffeine or alcohol intake. Excessive physical exertion may also be associated with eyelid myokymia. Demyelination and brainstem lesions are rarely found in patients thought to have eyelid myokymia.

Consisting of involuntary fine undulating contractions across the striated muscle, the pathophysiology of eyelid myokymia is not well understood. The contractions are nonsynchronous semirhythmic discharges of motor units discharging at a rate of 3-8 Hz. The discharges have intervals of 100-200 ms between individual motor bursts. The contractions are transient and intermittent. The focus of irritation is most likely the nerve fibers within the muscle. Pontine dysfunction in the region of the facial nerve nucleus also has been suggested. Possible precipitating factors include stress, fatigue, and excessive caffeine or alcohol intake.

Eyelid myokymia diagnosis

Patients with eyelid myokymia usually note sporadic “jumping” or “twitching” of one of the lower eyelids. Eyelid myokymia may also involve one of the upper eyelids or multiple eyelids. The irregular contractions are usually unilateral and may occur intermittently for days to months.

In rare cases, the contractions may be severe enough to move the eye to produce oscillopsia.

Physical examination

Fine fascicular nonsynchronous contractions of the orbicularis oculi may be visible if the patient has the contractions during examination. If present, the contractions are usually intermittent and are more apparently felt by the patient than visible to the observer. The symptoms often improve when the eyelid is pulled manually. Rarely, the contractions may be vigorous enough to cause movement of the globe, producing fine nystagmuslike eye movements.

If the eyelid myokymia is associated with contraction of other parts of the face, hemifacial spasm, blepharospasm, Meige syndrome, and spastic-paretic facial contracture should be excluded. Activation of the facial muscles (eg, big smile, eyelids squeezed shut) helps to determine if the eyelid myokymia is associated with contractions of other parts of the face.

Imaging studies

A complete cranial nerve examination should be performed.

If the myokymia is not seen in the office, patients should be encouraged to video-document their episodes.

Brain magnetic resonance imaging (MRI) is not needed for typical eyelid myokymia but should be considered if facial myokymia, hemifacial spasm, or spastic paretic facial contracture is suspected, as well as when eyelid myokymia is continuous.

Eyelid myokymia treatment

Reassurance and reduction in precipitating factors, if identifiable, are appropriate for many patients.

When symptoms are severe, local subcutaneous botulinum toxin A (BOTOX®) injections of 2.5-5 units each to the affected eyelid region provide relief for 12-18 weeks. If the upper eyelid is involved, the injections should not be placed near the levator palpebrae; otherwise, ptosis lasting weeks will result ¹⁵.

Adverse effects include temporary lid laxity, which may produce lagophthalmus, exposure keratopathy, ptosis, and diplopia.

The efficacy of other agents has not been proven.

Superior oblique myokymia

Superior oblique myokymia is a rare condition, characterized by episodes of sudden, rhythmic, monocular contractions of the superior oblique muscle ¹⁶. As a result, patients experience oscillopsia and diplopia, particularly when vision is directed downwards ¹⁷. Superior oblique myokymia does not preferentially affect one age group, but right-sided Superior oblique myokymia has been found statistically more prevalent in females than left-sided Superior oblique myokymia ¹⁸. There is currently no treatment protocol for superior oblique myokymia ¹⁸.

Superior oblique myokymia causes

The cause of superior oblique myokymia is idiopathic or unknown ¹⁶. It is possible that superior oblique myokymia could be caused by the trochlear nerve being compromised at the nerve root exit zone ¹⁹. Compression can be caused by the superior cerebellar artery, due to an absence of CSF between the nerve and artery¹⁸, a cyst, or a brain tumor ²⁰. Trauma has also been postulated as a cause of Superior oblique myokymia, but most cases do not report prior trauma in order to see symptoms ²⁰.

While compression and trauma have been associated with superior oblique myokymia, there are cases where patients do not display either of these etiologies. Thus, Superior oblique myokymia is not defined as a direct cranial nerve irritation disorder ¹⁸.

The superior oblique muscle is innervated by the trochlear nerve and functions to turn the eye inferiorly upon adduction ¹⁷. This muscle typically works in concert with other extraocular muscles, but in isolation, contraction would lead to an inferiorly and laterally displaced eye ¹⁷. Ocular electromyography with electrodes placed in the superior and inferior oblique muscles of the affected eye results in an atypically long duration of action potentials (7-8 msec) in superior oblique muscles, but not in inferior oblique muscles ²¹.

Compromised supranuclear input to the trochlear nerve, such as from vascular compression, results in segmental demyelination of the trochlear nerve and subsequent ephaptic transmission is thought to be more probable, leading to superior oblique myokymia ¹⁸.

While superior oblique myokymia is statistically more common in the right eye than left in women, there are no anatomical asymmetries in the trochlear nerve or surrounding structures when observed by MRI ¹⁸.

Risk factors for superior oblique myokymia

Superior oblique myokymia is typically not associated with other systemic disorders ²². However, some cases have shown Superior oblique myokymia to be precipitated by prior head or ocular trauma ²².

Superior oblique myokymia can be triggered by fatigue, stress, or changes in mood, but can often occur spontaneously as well ¹⁸. Fluorescent or flashing lights have also been associated with episodes of Superior oblique myokymia ²².

Superior oblique myokymia diagnosis

Superior oblique myokymia must be distinguished from trigeminal neuralgia, hemifacial spasm, the Heimann-Bielschowsky phenomenon, ocular neuromyotonia, and square wave jerks ¹⁸. Oscillopsia caused by eyelid myokymia is also often confused with superior oblique myokymia ¹⁸.

History

Individuals typically present with vertical diplopia when looking downwards. Patients may also experience image separation and hypertropia when looking away from the affected eye or when the patient’s head is tilted towards the affected eye ¹⁷. Uniocular “shimmering,” “fluttering,” or oscillopsia that last a few seconds at a time are common complaints involving abnormal eye movement. In all cases of reported superior oblique myokymia, the symptoms are unilateral, with the right eye being more commonly affected than the left in women ¹⁸.

superior oblique myokymia can affect patients anywhere from a few hours to weeks at a time before resolution, if at all. Each episode of superior oblique myokymia ranges from a few seconds to hours. The symptoms can also disappear as spontaneously as they appear ¹⁸.

Physical examination

Slit lamp examination may be normal, since episode frequency is random, but eye movements can sometimes be elicited by having the patient move their gaze from inferiorly and laterally to the center ²². The resulting intermittent vertical and torsional microtremors will be visible in one eye ¹⁹. Otherwise, neuro-ophthalmologic examination is normal ²².

Oscillations produced by superior oblique myokymia have a low amplitude of less than 4° and high frequencies up to 50 Hz ¹⁸. A “Honda sign” can be heard in patients with superior oblique myokymia when a stethoscope is placed over their oscillating eye. The quick movements of the superior oblique tendon produce a sound similar to a motorcycle engine ²³.

Atypical visual acuity, intraocular pressure, visual fields, pupillary reflexes, appearance of fundus, and ocular movement ranges are not commonly correlated with superior oblique myokymia, and are usually normal in the affected eye ²¹.

Clinical diagnosis

Superior oblique myokymia is a likely differential diagnosis when patients present with localized, involuntary, continuous contractions through the striated superior oblique muscle ¹⁸. It can be distinguished from the Heimann-Bielschowsky phenomenon, which causes monocular vertical eye movement by the character of the vertical oscillations. In contrast to superior oblique myokymia, the Heimann-Bielschowsky phenomenon has a high amplitude up to 30° and a low frequency of less than 5 Hz. On the other hand, square wave jerks are high-frequency, low-amplitude eye movements similar to those of superior oblique myokymia, but the former is due to a neurological lesion and patients complain of objects moving side to side rather than “bouncing up and down” in superior oblique myokymia patients ¹⁸.

Imaging

MRI investigation of the brain is sometimes unremarkable in patients with superior oblique myokymia ²³, but occasionally neurovascular conflict at the nerve exit zone is seen in thinly-sliced MRI images ¹⁷. Visualization by MRI Fourier transform constructive interference along with MRI time-of-flight MRA before and after administration of contrast agents shows greater trochlear nerve visualization by this protocol. By this method, arterial contact can be detected at the trochlear nerve root exit zone ²⁴.

Superior oblique myokymia treatment

There is no established treatment for superior oblique myokymia due to two main reasons: a lack of sufficient patient populations to perform a randomized controlled clinical trial, and the unpredictability and variable time course of superior oblique myokymia, making it difficult to evaluate the efficacy of existing medical therapies ¹⁸. Variable success has been seen with topical beta blockers, carbamazepine, phenytoin, baclofen, gabapentin, clonazepam, mirtazapine, memantine, and surgery ¹⁸. Botulinum toxin injections have variable success rates and could potentially only provide temporary relief due to difficulty in isolating the superior oblique muscle from the other extraocular muscles ¹⁸. In many cases, continuous medical therapy at dosages on a case-by-case basis has been correlated with favorable prognosis in superior oblique myokymia patients ¹⁸. However, unfavorable side effects of these drugs make treatment more difficult, and gabapentin is often used as a favorable first-line of treatment due to the relatively few side effects ²⁵.

Beta blockers such as propranolol, timolol, and betaxolol have recently been reported as successful treatment alternatives due to their ability to reduce blood pressure amplitude. This would mitigate symptoms caused by vascular compression of the trochlear nerve ¹⁸.

When medical management is unsuccessful, surgical intervention may be used ²⁶. The procedures most commonly used for superior oblique myokymia are superior oblique tenotomy along with inferior oblique myectomy, or microvascular decompression of the trochlear nerve ¹⁸. The latter may only be used when vascular compression is identified as the cause of superior oblique myokymia by MRI.

Superior oblique myokymia prognosis

In some cases, patients with superior oblique myokymia see spontaneous improvement or recovery ²². In most patients, however, chronic episodes of superior oblique myokymia occur and symptoms can attempt to be controlled using various medical treatments or surgical interventions ²².

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