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A novel association of ocular neuromyotonia with brainstem demyelination: Two case reports
Abstract
Ocular neuromyotonia (ONM) is a rare disorder of ocular mal-alignment in which painless, transient spontaneous or gaze-induced abnormal deviation of the eye manifests as episodic diplopia. With only a few cases reported in the literature, ONM mostly follows months to years after cranial irradiation for sellar or suprasellar lesions. Here we present two patients with this rare ocular condition, secondary to brainstem demyelination, the association of which is hitherto unreported in the literature. Both patients were 15-year-old girls who presented to us with episodic forced-eye deviation with diplopia. Examination during these attacks revealed ONM involving the superior rectus and medial rectus in the first and second patient, respectively. There was clinical evidence of intrinsic brainstem involvement with downbeat nystagmus and skew deviation in one patient without any other cerebellar or long tract signs. MRI showed evidence of demyelination involving the brainstem in both, with CSF showing positive immunological markers and with positive aquaporin-4 antibody in one patient. Both patients responded remarkably to immunomodulatory therapy and are asymptomatic at follow-up. That ONM can occur with brainstem demyelination has not been reported in the literature. This association may help in explaining the pathophysiology of ONM as secondary to segmental demyelination.
... Het wordt gekarakteriseerd door een verworven abnormale myotone contractie van 1 of meerdere oogspieren, wat resulteert in intermitterende diplopie. [1][2][3][4][5][6][7] In 1966 werd dit ziektebeeld voor het eerst beschreven door Clark. 1,2,5 In 1970 werd door Ricker en Mertens de term oculaire neuromyotonie eraan gekoppeld. ...
... De meest voorkomende oorzaak van oculaire neuromyotonie is radiotherapie in het gebied van de sella of de schedelbasis. [1][2][3][4][5]6,8 De spasmen kunnen tot lang na de bestraling optreden met een spreiding van 2 maanden tot 18 jaar. 3,6 Daarnaast is oculaire neuromyotonie beschreven bij andere ziektebeelden zoals demyelinisatie in de hersenstam in het kader van multiple sclerose, arachnoiditis, Graves' orbitopathie, meningeomen, compressie door een aneurysma of dolicho-basilaris of trombose in de sinus cavernosus. ...
... [1][2][3][4][5]6,8 De spasmen kunnen tot lang na de bestraling optreden met een spreiding van 2 maanden tot 18 jaar. 3,6 Daarnaast is oculaire neuromyotonie beschreven bij andere ziektebeelden zoals demyelinisatie in de hersenstam in het kader van multiple sclerose, arachnoiditis, Graves' orbitopathie, meningeomen, compressie door een aneurysma of dolicho-basilaris of trombose in de sinus cavernosus. 1-3,5-7 Het gaat hierbij allemaal om case reports. ...
Stoornissen in de oogbolmotoriek zijn een vaak voorkomende uiting van neurologische ziekten. Oculaire neuromyotonie is een relatief onbekend ziektebeeld dat niet snel wordt herkend. Er is sprake van een intermitterende diplopie die opgewekt kan worden door in een bepaalde richting te kijken, maar ook spontaan kan optreden. De meest voorkomende oorzaak is bestraling in het gebied van de schedelbasis. Het is goed behandelbaar met carbamazepine. Symptomen, oorzaken, mogelijke ontstaansmechanismen, differentiaaldiagnostische overwegingen en de behandeling van dit ziektebeeld worden beschreven | Braaksma, M.M., Vels, I., & Boon, A.J.W. (2017). Oculaire neuromyotonie. Tijdschrift voor Neurologie en Neurochirurgie, 118(2), 74-76.
... These symptoms occurred (a) after radiation therapy of the parasellar region [47][48][49][50][51][52] or other regions [49,53], (b) due to vascular compression through small arteries [54,55] or internal carotid aneurysms [56], (c) in patients with chronic pachymeningitis [57], or (d) associated with autoimmune disease such as myasthenia gravis [58,59] or graves orbitopathy [60]. Analogously to paroxysmal brainstem attacks with recurrent vertigo due to demyelination or after infarction, a similar mechanism was also found in patients with ONM secondary to brainstem demyelination [61]. Possible pathophysiologic mechanisms of ONM include further unstable motor nerve membranes, ephaptic transmissions across adjacent nerves, and abnormal extracellular potassium concentrations [56,62]. ...
... Pharmacotherapy Table 3 summarizes the published case reports and case series. The vast majority of these patients were treated with carbamazepine, which proved overall successful in up to 80 % of cases [54,56,57,[61][62][63][64][65][66][67][69][70][71][72][73]. Further case reports describe the different effects of other medical treatment options, e.g., gabapentin, phenytoin, and lamotrigine, which ranged from no efficacy to moderate success [55,64,65]. ...
... Further case reports describe the different effects of other medical treatment options, e.g., gabapentin, phenytoin, and lamotrigine, which ranged from no efficacy to moderate success [55,64,65]. The two patients with suspected demyelination were treated successfully with immunomodulatory therapy [61] Surgical treatment There are a few case reports in which microvascular decompression of the trochlear nerve was a therapy option for ONM [65,68]. ...
Opinion statement:
Neurovascular compression syndromes are characterized by recurrent attacks of neurological symptoms and clinical signs depending on the cranial nerve affected. It is assumed that pulsatile compression of the nerve is caused mainly by an artery. The result is segmental demyelination of the transition zone or the central part of the cranial nerve, which is covered by oligodendrocytes, and subsequent ephaptic axonal transmission. Compression of the vestibular nerve can cause attacks of spinning or non-spinning vertigo: vestibular paroxysmia. Compression of the trochlear nerve is characterized by attacks of monocular oscillopsia: superior oblique myokymia. Damage to ocular motor nerves due to local radiation or rarely neurovascular compression can also lead to oscillopsia and double vision precipitated by sustained excentric gaze: ocular neuromyotonia. It is important to note that controlled trials have so far not been performed for any of these three syndromes, mainly because of their low prevalence. Therefore, treatment recommendations are based on single cases or small case series and thus have the lowest level of evidence. The sodium channel blockers carbamazepine (50 to 200 mg tid) or oxcarbazepine (100 to 300 mg tid) are evidently effective in most of the patients who have these three syndromes. However, one should always keep in mind the contraindications, side effects, and interactions with other drugs of carbamazepine ( http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682237.html ) All patients require regular laboratory examinations. Alternatives are other sodium channel blockers such as phenytoin (100 to 300 mg tid), gabapentin (100 to 600 mg tid), or valproic acid (100 to 300 mg tid). Furthermore, there are also few reports on the effects of beta blockers, which may be explained by their reduction of the amplitude of blood pressure. Patients who do not respond to pharmacotherapy require further diagnostics to determine the possibility of other etiologies. Some of these patients benefit from surgical decompression of the affected nerve.
... This further emphasized the pathophysiology of ONM as secondary to segmental demyelination [14], which conduce to cell membranes of nucleus neurons or axons unstable. Thus, carbamazepine has often been approved effectiveness in treating ocular neuromyotonia as a membrane stabilizer of hyperexcitable axons. ...
... Arnoild-Chiair deformation type I in patient #3 might be a supporting factor for a central mechanism involved. It was reported that the third nerve palsy was attributed to deformation of the brainstem [14,20]. ...
... During sustained muscle activity, extracellular potassium accumulates and provokes neuromyotonic discharges [13]. In 2014, Deepak Menon, etc. reported two cases of ONM caused by brainstem demyelination [14]. This further emphasized the pathophysiology of ONM as secondary to segmental demyelination, which conduce to cell membranes of nucleus neurons or axons unstable. ...
... Arnoild-Chiair deformation type I in patient #3 might be a supporting factor for a central mechanism involved. It was reported that the third nerve palsy was attributed to deformation of the brainstem [14,20]. The lesion may destruct the sympathetic inhibitory path from hypothalamus to the dilator muscle of pupil or degenerate the oculomotor neuron. ...
Purpose of review:
The current review will cover the clinical presentation, causes, epidemiology, differential diagnoses, workup, and treatment of ocular neuromyotonia (ONM) in detail.
Recent findings:
While ONM largely remains a unilateral eye movement disease affecting adults with a history of sellar radiation, recent case reports highlight an expansion of this presentation to include bilateral, pediatric, and congenital cases.
Summary:
ONM is a rare but recognizable ocular motility disorder involving sustained contraction of the extraocular muscle, commonly resulting in intermittent diplopia. Diagnosis of ONM relies upon a thorough history and clinical exam, with particular attention to history of radiotherapy and eccentric gaze testing. Treatment with carbamazepine remains first-line therapy, although other membrane stabilizing agents and surgical interventions can be effective.
Purpose:
To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years.
Methods:
Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation.
Results:
Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to metastatic disease, and one patient has planned follow-up.
Conclusions:
Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].
Introduction:
Ocular neuromyotonia (ONM) is a rare condition characterized by episodic involuntary extraocular muscle (EOM) contraction and spasm. ONM has many presumed causes of which radiation therapy and thyroid dysfunction are the most common. ONM symptoms can be mild, moderate, or severe and can be debilitating. This monograph described the clinical features, evaluation, and management of ONM
Areas covered:
This review will cover pathogenesis, epidemiology, clinical presentation, diagnosis and differential diagnoses, workup, and treatment options of ocular neuromyotonia.
Expert opinion:
ONM is a rare but highly distinctive disturbance of EOM that is typically associated with parasellar radiation therapy but can occur in other conditions such as thyroid eye disease. Neuroimaging studies are generally recommended but most cases develop in the setting of stable treated disease. Medical and surgical management of ONM is difficult with variable treatment response.
Ocular neuromyotonia (ONM) is a rare eye movement disorder, presenting as a paroxysmal involuntary spasm of one or more extra-ocular muscles, that can persist for a few seconds up to several minutes. The phenomenon is caused by the contraction of an extra-ocular muscle, excited by a damaged nerve, which leads to delayed muscle relaxation.
We present eight patients with this rare condition together with an overview of the literature on all published ONM cases. One of the presented cases is possibly secondary to hypovitaminosis D. This association has not been reported previously in the literature. A possible underlying mechanism is given.
Objective:
To present a patient with a sudden onset ocular tilt reaction (OTR) and review recent knowledge and evolving insights of the underlying pathophysiological mechanisms of skew deviation and OTR.
Methods:
A middle-aged hypertensive man who had previously suffered stroke with good recovery presented with sudden-onset double vision, slurred speech, ataxia, and a head tilt. Romberg test was positive. The patient denied having disturbances of visual acuity, eye pain, or recent trauma. The right eyeball was pushed upward. The patient complained of double vision in any gaze direction. Movements of the extraocular muscles (EOMs) in the horizontal plane were normal, whereas vertical version and convergence were not possible. We administered a Hess-Lancaster test, cover test, fundoscopic examination, Parks-Bielschowsky three-step test, upright-supine test, brain magnetic resonance imaging (MRI), transcranial doppler (TCD) ultrasonography, electrocardiogram (ECG), Holter monitor (24 h), and echocardiography.
Results:
The Hess-Lancaster test showed superior rectus muscle and inferior obliquus muscle palsy to the left and rectus inferior muscle and superior obliquus muscle palsy to the right. The right eyeball fell behind when looking downward and the left eyeball when looking upward. Cover alternating test was positive from vertical, R/L. Examination of the ocular fundus showed incyclotorsion of elevated right eye and excyclotorsion of depressed eye. The Parks-Bielschowsky three-step test was negative. A brain MRI with gadolinium revealed a small zone of diffusion restriction in the medial portion of the right cerebral peduncle and right thalamus. There was a gradual improvement in the patient's neurological status following treatment.
Conclusion:
Skew deviation, a not uncommon clinical condition, should be promptly recognized when binocular vertical diplopia cannot be interpreted by trochlearis and oculomotor nerve lesion, myasthenia gravis, or orbital pathology. Maddox rod, cover test, Parks-Bielschowsky three-step, and other tests should help to establish the diagnosis. The prognosis depends on etiology, but it is commonly favorable; the majority of patients recover spontaneously after less than a year. More invasive management options should be discussed thereafter.
Ocular neuromyotonia is characterised by spontaneous spasm of extraocular muscles and has been described in only 14 patients. Three further cases, two with unique features, are described, and the underlying mechanism reviewed in the light of recent experimental evidence implicating extracellular potassium concentration in causing spontaneous firing in normal and demyelinated axons.
Two patients had third nerve neuromyotonia, one due to compression by an internal carotid artery aneurysm, which has not been reported previously, while the other followed irradiation of a pituitary tumour, a common association in the published reports. Selective activation occurred in both, where neuromyotonic activity was triggered by prolonged voluntary activation of specific extraocular muscles with or without spread of activity to other third nerve muscles. The other patient had fourth nerve involvement, where spasms of the superior oblique muscle were induced only by alcohol, a phenomenon which has not been described.
The two patients with third nerve involvement responded to carbamazepine and in one, an improvement in a chronic partial third nerve paresis occurred. The other has not required treatment and remains asymptomatic by refraining from alcohol.
A careful examination, including the effects of prolonged voluntary muscle action is required to initiate episodes and to demonstrate selective activation. Imaging is mandatory to exclude compressive intracranial lesions, particularly where there is no history of pituitary fossa irradiation. A trial of anticonvulsants should be considered in all patients. Extracellular potassium may play a role in spontaneous firing and ephatic transmission in ocular neuromyotonia.
: Ocular neuromyotonia is an unusual condition in which sustained, undesired contraction of one or more extraocular muscles occurs after normal muscle activation. Although most commonly reported after paraseller cranial irradiation for tumor, chronic nonaneurysmal vascular compression of the third nerve can produce partial ocular motor nerve paresis and ocular neuromyotonia. A 75-year-old woman presented with intermittent left-gaze-evoked binocular diplopia. She had an incomplete right third nerve palsy but became symptomatically diplopic and esotropic upon sustained left gaze. High-resolution brain magnetic resonance imaging showed displacement of the right posterior communicating artery and contact with the right third nerve. Gaze-evoked diplopia resolved with carbamazepine, but a partial third nerve paresis remained.
A 27-year-old woman noticed diplopia when gazing left and paresthesia of the left face and headache of the left side for 8 months. Abduction and supraduction of the left eye were moderately restricted. Hypoesthesia of the face innervated by the ophthalmic branch of the left trigeminal nerve was detected. Visual disturbance due to optic neuropathy developed 5 months later. MRI with gadolinium revealed a mass lesion extending from the left cavernous sinus to the orbital apex. Ocular neuromyotonia and corresponding diplopia were induced by sustained right gaze. Such episodes occurred almost every day on awaking in the morning. Prednisolone (60 mg/day) was given and the headache and visual disturbance ameliorated in two days. The diplopia disappeared in 4 days. The patient remains free from these symptoms after 6 months. This is the first report of ocular neuromyotonia associated with Tolosa-Hunt syndrome.
Abstract Ocular neuromyotonia (ONM) is a rare but distinctive clinical entity characterized by involuntary episodic contraction of one or more muscles supplied by the ocular motor nerves. A retrospective review was conducted on all patients with ONM seen by the neuroophthalmology service in the past 20 years. Ten patients were identified with ONM; six affecting vertical muscles (superior oblique; inferior rectus; superior rectus) and four affecting lateral rectus muscles. Case 1 has been reported previously. Most episodes occurred every 10-40 min, lasted a few seconds to several minutes, and were repeated throughout the day. Only two patients had previously undergone cranial radiation. Two had thyroid eye disease. One patient presented with superior oblique myokymia and subsequently developed ONM. Membrane stabilizing medications were prescribed in 7 of the 10 patients with varied success. ONM episodes ceased after extraocular muscle surgery in one patient with thyroid eye disease.
To present a novel case of pupillary involvement in ocular neuromyotonia (ONM), a rare ocular syndrome that causes intermittent diplopia because of an abnormal delay in extraocular muscle relaxation and to conduct a literature review.
A case report is presented to demonstrate clinical characteristics and treatment of ONM. In addition, a literature review is conducted by searching Medline and Embase databases. Data are collected from all known published cases listed in these databases to collate patient demographic data, presumed etiology or associated pathologies, and treatment strategies.
The presented case demonstrates successful carbamazepine treatment of thyroid-related orbitopathy-associated ONM involving cranial nerve III. A review of the literature elicits 66 published cases of ONM, three of which were deemed to be associated with thyroid-related orbitopathy. The most common cause of reported ONM is suprasellar pathology, comprising approximately 60% of documented cases. Most published ONM cases (n = 41) were treated with carbamazepine, demonstrating a success rate of 87.8%. Of the published cases, cranial nerve III was involved 56% of the time, cranial nerve VI was affected in 39% of cases, and only 9% of ONM cases involved cranial nerve IV.
Ocular neuromyotonia is a rare cause of intermittent diplopia. Unlike most neurologic etiologies of diplopia, this syndrome can often be treated effectively with carbamazepine by stabilizing the neural cell membrane. To the authors' knowledge, this is the first presentation of ONM associated with thyroid-related orbitopathy, demonstrating bilateral but asymmetric miosis during episodes of muscle spasm.
In this case series and review of the literature, we describe 2 cases of abducens neuromyotonia (ANM) as the presenting sign of an intracranial tumor (meningioma). Review of the literature suggests that the pathophysiology of ocular neuromyotonia is incompletely understood. Most patients with ANM have a history of radiation therapy. The diagnosis of ANM is made on the basis of clinical findings and can be supported by electrophysiological studies. A complete neurologic examination is mandatory for patients with ANM. Treatment consists of eliminating the underlying cause; carbamazepine is effective in alleviating the symptoms of ANM. Neuroimaging should be performed if patients with ANM lack the typical history of radiation therapy, as ANM may be the presenting sign of an intracranial mass.
Ocular neuromyotonia is a paroxysmal monocular deviation that results from spasm of eye muscles secondary to spontaneous discharges from third, fourth, or sixth nerve axons. We observed this rare disorder in four patients who had been treated with radiation for tumors in the region of the sella turcica and cavernous sinus. Based on these cases and four others identified in the literature it would appear that radiation predisposes to a cranial neuropathy in which ocular neuromyotonia may be the major manifestation. Radiation appears to be the most common cause of ocular neuromyotonia.
To the Editor.
—Although Shults and colleagues1 refer to the possible role of central synaptic reorganization following peripheral nerve injury in the pathogenesis of ocular neuromyotonia, they favor the alternative hypothesis of injured motor axons generating spontaneous impulses. The clinical data provided, however, may be interpreted as supporting a central cause.In three of the four cases described involving the oculomotor nerve, the neuromyotonic phase involved the extraocular muscles innervated by the third nerve, but not the pupil and ciliary muscle, as would be expected with ephaptic transmission. All of these patients showed lid retraction on downgaze in the neuromyotonic phase, ie, an increased innervation of one third nerve-innervated muscle on attempted use of another in a stereotyped pattern, suggesting that the function of the subnuclei of these two muscles was abnormally coordinated. Moreover, slight lid retraction on downgaze was a feature outside the neuromyotonic phase in all four cases
Ocular neuromyotonia (ONM) is a rare disorder characterized by episodic diplopia, occurring either spontaneously or following sustained eccentric gaze. Most patients have had prior radiation therapy to the sellar and parasellar region. ONM is thought to reflect impaired muscle relaxation due to inappropriate discharges from oculomotor, trochlear, or abducens neurons or axons with unstable cell membranes. Patients with ONM often benefit from membrane stabilizing agents such as carbamazepine. Here we describe a 71-year-old man, with no history of radiation therapy, who for 18 months had had transient episodic diplopia that occurred after down gaze. Clinical examination indicated ONM in muscles supplied by the right oculomotor nerve. Binocular scleral search coil eye movement recordings revealed a defect not only of muscle relaxation but also of maximal muscle contraction. The patient was treated with carbamazepine 200 mg per day with complete resolution of his symptoms. ONM may be more common than previously recognized, and patients with unexplained transient episodic diplopia should be specifically tested for diplopia and ocular misalignment following sustained eccentric gaze.