Ocular neuromyotonia (ONM) is a rare eye movement disorder. It consists of paroxysmal contraction of 1 or more extraocular muscle(s) innervated by an affected ocular motor cranial nerve. The activated muscle does not relax until the paroxysm subsides, which may take seconds to several minutes. The third (oculomotor) nerve is most commonly affected in ONM, followed by fourth (abducens) and sixth (trochlear) nerves.
The vast majority of patients with ONM have a history of radiation therapy (1-13). The time from radiation therapy to clinical manifestation of ONM ranges from 2 months to 18 years (7). Some of the reported patients had intracranial or nasopharyngeal masses, but ONM usually did not present until after radiation therapy. In a few cases, nerve compression caused by intracranial aneurysms has been associated with ONM (5,12,14-16). Moreover, ONM has been described after myelography with thorium (13), after a stroke (17), in patients with thyroid-related orbitopathy (18) and with cavernous sinus thrombosis due to mucormycosis (19). In some, no cause for ONM can be found (20-25).
Neuromyotonia affecting the abducens nerve (ANM) leads to paroxysmal contraction of the ipsilateral lateral rectus muscle, causing abduction of the eye. To our knowledge, no case of ANM as the presenting sign of an intracranial tumor has been described. We present 2 cases where ANM was the first sign of an intracranial tumor. In both cases, consent to publish was granted.
A 48-year-old woman complained of episodic binocular horizontal diplopia, which she first noted approximately 1 year before presentation. The episodes lasted from a few seconds to 1 minute and occurred several times per day. During the episodes, the patient noted a “pulling sensation” around the left eye, she felt nauseated and had a mild left frontal headache, which was not present between episodes. Her medical history was significant for excision of a benign breast cyst at the age of 18 years; there was no history of an intracranial mass or radiation therapy. Social history was significant for smoking (half pack-year). She denied alcohol use and did not take any medications.
Best corrected visual acuity was 20/20 in each eye. External and anterior segment exams were unremarkable except for mild nuclear sclerotic cataracts. Stereopsis and color vision were normal, and visual fields were full to confrontation in both eyes. Pupils reacted equally to light, there was no afferent pupillary defect, and the fundi were normal. The patient was orthophoric in primary gaze at distance and near, and ocular versions were full. There was no strabismus in any gaze position except for esotropia of 14Δ on left gaze. After maintaining left gaze for 20-30 seconds, the left eye assumed a maximally abducted position and could not be adducted beyond midline. Attempted adduction during the attack resulted in retraction of the left globe (Fig. 1; see also Video, Supplemental Digital Content 1, http://links.lww.com/WNO/A13). On further questioning, the patient reported mild tingling over the left cheek, although sensation to touch in this area was intact and not different from the right cheek. All other cranial nerve functions were intact.
MRI of the brain showed a large homogenously enhancing mass originating from the prepontine cistern, compatible with a meningioma (Fig. 2). Neurosurgical removal of the tumor was undertaken, and pathological evaluation confirmed the diagnosis of meningioma. Postoperatively, the patient had paresis of the third through seventh cranial nerves. ANM did not recur, but the patient was left with a mild left sixth nerve palsy.
A 49-year-old woman complained of transient diplopia associated with a sensation of pressure around the right eye lasting seconds to 1 minute and occurring 10-15 times per day. Visual acuity was 20/20 in each eye, and ocular exam was normal. Ocular motility testing revealed paroxysmal abduction of the right eye after right gaze, lasting approximately 30 seconds (Fig. 3). At other times, ocular alignment and motility were completely normal. Electromyography (EMG) of the right lateral rectus muscle during the attack showed a high-frequency, repetitive, continuous discharge. Extraocular EMG and electroneurography showed no evidence of a generalized myogenic or neurogenic disorder. Brain MRI revealed a mass within the right cavernous sinus, compatible with a meningioma (Fig. 4). The patient was started on 600 mg/day carbamazepine, and the paroxysmal ocular deviation disappeared. Stereotactic conformal radiation therapy (total dose: 56 Gy) was given, and carbamazepine was tapered and discontinued. Brain MRI 2.5 years later showed considerable reduction in the size of the tumor, and the patient remained free of diplopia.
The term ONM was introduced by Ricker and Mertens (26) to describe a peculiar disturbance of ocular motility, consisting of paroxysmal contraction of an extraocular muscle, causing the eye to deviate with resultant diplopia. The muscle does not relax until the paroxysm subsides, which may take minutes. A pulling sensation around the involved eye and headaches may be reported. The majority of cases with ANM have a history of previous radiation therapy. Only 1 reported case had resection of an intracranial tumor (clivus chordoma) without radiation therapy before developing ANM (27).
We could not find any published cases of ANM as the presenting sign of an intracranial mass. Oculomotor neuromyotonia associated with compressive lesions without radiotherapy has been reported (5,12,14,16). One patient with oculomotor neuromyotonia secondary to a cavernous sinus meningioma also had “paroxysmal electrical discharges in the ophthalmic division of the left trigeminal nerve,” indicating involvement of the fifth cranial nerve (28). One of our patients (Case 1) complained of paresthesias in the distribution of the maxillary division of the left trigeminal nerve, emphasizing the importance of a complete cranial nerve exam in patients with ONM.
ONM has to be distinguished from oculomotor paresis with cyclic spasm, which is characterized by a cycle of paresis and spasm of muscle(s) innervated by the third nerve. The spasms are neither induced nor altered by eccentric gaze (29). In ONM, the deviation can often be induced by looking in the direction of action of the involved extraocular muscle. Another differential diagnostic consideration is myokymia. Although rare, superior oblique myokymia is more common than trochlear neuromyotonia. Myokymia consists of an ocular microtremor that is not present in neuromyotonia. EMG shows phasic contractions in myokymia in contrast to tonic contractions in ONM (7).
The pathophysiology of ONM is not well understood. Potential mechanisms include 1) ephaptic transmission along the affected nerve, 2) disturbances of potassium channels in the neuronal cell membrane, and 3) central neural reorganization. In most published cases of ONM, an extra-axial lesion is present, but Banks et al (17) indicated that a brainstem lesion may lead to the eye movement disorder. A more detailed discussion on pathogenesis of ONM has been published elsewhere (30).
In summary, ANM should prompt a complete neurologic exam of the patient, with special attention to the cranial nerves. Most often, it is associated with previous radiation therapy. Neuroimaging should be performed in patients with ANM who lack such a history because it may be the presenting sign of an intracranial mass.
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