Search

Competing Interests: The authors report no conflicts of interest.

Ocular neuromyotonia (ONM) is an infrequent disorder characterised by recurrent episodes of binocular diplopia caused by paroxysmal contraction of one or several extraocular muscles innervated by the same cranial nerve. It can be triggered spontaneously or caused by prolonged contraction of specific eye muscle(s) and is usually related to a local intracranial radiotherapy antecedent. We report the case of a 46-year-old woman who developed intermittent episodes of binocular diplopia eight years after radiotherapy for a nasopharyngeal carcinoma. After a complete neuro-ophthalmic assessment we diagnosed the case as an abducens nerve neuromyotonia. Although it is infrequent, radiotherapy to the nasopharynx is a possible cause of ONM, due to the proximity to the base of the skull and extraocular motor nerve pathways, especially that of the VI cranial nerve, as is the case presented in this article, about a patient whose history is a nasopharyngeal carcinoma treated with local radiotherapy., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

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 meta-static 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 . 2022;59(5):338-343.] .

Introduction: The first report of oculomotor neuromyotonia (ONM) in a child induced by thyroid peroxidase antibodies (anti-TPO) in the absence of thyroid eye disease (TED)., Case: 14-year-old girl complained of left eye (LE) paroxysmal upper lid fluttering and ptosis precipitated by hyperventilation or sustained left gaze. On sustained left gaze, right eye (RE) upper lid retraction and LE upper lid fluttering with ptosis ensued., Results: Diagnostic work-up revealed markedly elevated anti-TPO (> 600 IU/ml) and no TED. Brain MRI was normal with no signs of tortuous vessels presenting focal demyelination. We hypothesized that anti-TPO directly induced demyelination and set the ground for right ONM with ephaptic transmission between neurons supplying right medial rectus and levator muscle., Conclusions: Plethora of theories try to decode the ONM. TED associated ONM is not reported in children but is the second most common cause of ONM in adults, advocated to be of compressive origin. Conversely, this case holds true for cross talk hypothesis. All extraocular muscles must be tested to determine the triggering one. ONM should not be overlooked due to its positive response to carbamazepine.

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs' syndrome, suggesting that immunotherapy should be considered for Isaacs' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.

Ocular neuromyotonia (ONM) is characterized by episodes of binocular diplopia usually triggered by an eye movement requiring contraction of the affected extraocular muscle. It consists of an involuntary, sometimes painful contraction of one or more extraocular muscles. It is most often secondary to radiotherapy of the para-sellar region, although other aetiologies have been reported. Some cases do not have a clearly identified aetiology and are classified as idiopathic. Most cases of ONMs are unilateral but bilateral ONMs have also been described. 1-4 We report a case of left ONM in a 55-year-old female patient, several weeks after simultaneous surgical resection of two meningiomas, situated on the right side (Simpson II). The particularity of this case is linked to its puzzling presentation, its similarity with spasm of the near reflex and the putative mechanism through which surgery might have precipitated the symptoms.

Rationale: Acquired neuromyotonia syndrome is a rare form of peripheral nerve hyperexcitability syndrome. It is characterized by spontaneous and continuous muscle contractions. Acquired neuromyotonia syndrome is mainly observed in patients with autoimmune diseases or tumors, but it is a rare neurological clinical manifestation in patients with mercury poisoning., Patient Concerns: A 56-year-old woman presented with continuous and involuntary muscle twitching in her legs for 2 months; it was accompanied by a burning sensation in the lower limbs, insomnia, fatigue, and night sweats. These symptoms did not disappear during sleep., Diagnoses: Toxicological blood analysis via atomic fluorescence spectrometry revealed that the level of mercury was 0.07 μmol/L (normal level: <0.05 μmol/L). Her urinary mercury level measured using the cold atomic absorption method was 217.50 μmol/mol creatinine, which was considerably higher than the reference range (0-2.25 μmol/mol creatinine for people not in contact with mercury, 0-20 μmol/mol creatinine following long-term exposure). Upon further testing, a high level of mercury (10,572 mg/kg) was detected in the patient's cream. Accordingly, this patient was diagnosed with mercury poisoning., Interventions: Treatment with 2,3-dimercapto-1-propanesulfonic acid (DMPS) was initiated. Her urinary mercury level decreased to 9.67 μmol/mol creatinine, and her neuromyotonia syndrome and hyponatremia were relieved, with urine protein completely disappearing after 3 months of treatment., Outcomes: After DMPS treatment, the clinical manifestations of the nervous system disappeared and electrolyte parameters returned to normal levels., Lessons: Acquired neuromyotonia syndrome is a rare disorder caused by the hyperexcitability of peripheral nerves, resulting in spontaneous and continuous muscle contraction. Mercury poisoning should be considered in patients with neuromyotonia syndrome. Early detection of mercury poisoning can prevent unnecessary examinations and treatments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose/Aim: Acquired neuromyotonia or Isaacs syndrome is a type of peripheral nerve hyperexcitability of autoimmune origin. It may occur as an isolated, paraneoplastic or accompanied with some autoimmune diseases. This report describes acquired neuromyotonia in a child with a new reported association with vitamin D deficiency. Case report: A 9-year-old child, in whom the diagnosis of acquired neuromyotonia was made by clinical and typical electromyographic findings. All paraneoplastic and autoimmune workup was normal, except for a vitamin D deficiency state. A dramatic improvement was recorded on both clinical and electrophysiological base after vitamin D replacement. Conclusion: An in-depth future analysis of vitamin D status in patients with neuromyotonia will help to establish whether the association of neuromyotonia with vitamin D deficiency is casual or whether these two conditions may be causally related.

Background: Ocular neuromyotonia (ONM) is characterized by episodic diplopia, which is usually triggered by prolonged eccentric gaze of the affected extraocular muscles. The spell is characterized by involuntary, occasionally painful, sustained contraction of one or more extraocular muscles innervated by the oculomotor, trochlear, or abducens nerve. ONM usually occurs as a late consequence of radiotherapy around the parasellar area, although idiopathic cases have been reported. Most cases are unilateral; however, bilateral ONM has occasionally been described., Case Presentation: A 60-year-old woman presented with a 4-month history of episodic, painful, horizontal binocular diplopia. She underwent external beam radiotherapy to the skull base for treatment of nasopharyngeal carcinoma. The tumor was well controlled. General neurological examination findings were unremarkable. Neuro-ophthalmic examination revealed normal visual acuity, visual fields, pupils, and fundi. Ocular alignment showed orthotropia with normal ocular motility. Myasthenic eyelid signs were absent. However, she developed episodes of involuntary sustained contraction of the medial rectus muscle following prolonged eccentric gaze toward the affected medial rectus muscle, which resulted in esotropia upon returning to the primary position. The esotropic episodes spontaneously resolved after approximately 2 min. These spells affected both medial rectus muscles. Both pupils remained normal throughout the examination. Magnetic resonance imaging revealed neither brain parenchyma/brain stem lesions nor tumor recurrence. Her symptoms were successfully treated with carbamazepine., Conclusions: Episodic esotropia in the adducting eye following prolonged horizontal eccentric gaze is a significant characteristic of ONM affecting the bilateral medial rectus muscles (i.e., bilateral oculomotor ONM). In spite of its extreme rarity, ONM should be considered as a differential diagnosis of episodic diplopia, especially in patients with a history of radiotherapy around the parasellar area. Careful examination with prolonged eccentric gaze should be performed to achieve a correct diagnosis and avoid an extensive unnecessary workup.

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.

This is a case report of Isaacs' syndrome in dermatomyositis. The patient presented with proximal muscle weakness, rash, elevated muscle enzyme, myopathic electromyograph and typical muscle biopsy. Ultimately he developed typical symptoms of Isaacs' syndrome which is an autoimmune channelopathy from voltage gated potassium channel antibody (anti-VGKC) leading to dysfunction of axonal discharge at neuromuscular junctions. It shares some similar characteristics with dermatomyositis such as autoimmunity, its association with malignancy and the response to treatment., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Ocular neuromyotonia is a rare, but well-recognized, complication of cranial irradiation., Case Report: Using figures and videos, we report a 52-year-old man with extensive ocular, brainstem, and lower cranial nerve neuromyotonia postradiation therapy for a fourth ventricle glioma who, in the context of an apparently positive edrophonium test, was initially misdiagnosed with myasthenia gravis., Conclusions: This is the first case of postirradiation neuromyotonia to be reported with such extensive cranial nerve and brainstem involvement.

Background: Ocular neuromyotonia (ONM) is a disorder characterized by periodic involuntary extraocular muscle contraction that occurs almost exclusively in the setting of prior radiation to the sella or skull base. We present the first case of abducens neuromyotonia associated with oropharyngeal carcinoma., Methods and Results: We report a case of a 63-year-old patient with abducens ONM occurring 16 years after radiation treatment for oropharyngeal squamous cell carcinoma. A literature review was performed using Medline and PubMed databases to search for all documented cases of abducens neuromyotonia. Our review found 20 cases of abducens neuromyotonia but none after radiotherapy (RT) to the oropharynx., Conclusion: Abducens ONM can occur because of disease at anatomic locations remote from the course of the sixth cranial nerve, most likely because of the irradiated area exceeding the intended field. Our case also supports the fact that RT can significantly precede symptom onset. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2428-E2431, 2016., (© 2016 Wiley Periodicals, Inc.)

CASE DESCRIPTION A 5-year-old castrated male Maltese was evaluated for intermittent clinical signs of muscle cramping and abnormal movements of the skin of the right pelvic limb at the site where an infiltrative lipoma had twice been resected. After the second surgery, the surgical field was treated with radiation therapy (RT). The clinical signs developed approximately 14 months after completion of RT. CLINICAL FINDINGS When clinical signs were present, the right biceps femoris and semitendinosus muscles in the area that received RT were firm and had frequently visible contractions, and the skin overlying those muscles had episodic vermiform movements. Electromyography of those muscles revealed abnormal spontaneous activity with characteristics consistent with myokymic discharges and neuromyotonia. Magnetic resonance imaging of the affected leg revealed no evidence of tumor regrowth. The myokymia and neuromyotonia were considered secondary to RT. TREATMENT AND OUTCOME 4 U of Clostridium botulinum toxin type A (BoNT-A) neurotoxin complex was injected into the affected muscles at each of 6 sites twice during a 24-hour period (ie, 48 U of BoNT-A were administered). The clinical signs were completely resolved 10 days after BoNT-A treatment and were controlled by repeated BoNT-A treatment every 3 to 4 months for > 1 year. CLINICAL RELEVANCE To our knowledge, this is the first report of myokymia and neuromyotonia secondary to RT in a dog. For the dog of this report, injection of BoNT-A into the affected muscles was safe, effective, and easy to perform.

Neuronal or axonal ion channel function can be impaired or altered in a number of disorders, such as acquired (autoantibody-mediated, toxic, and metabolic) and genetic channelopathies, and even neurodegenerative (motor neuron disease) or inflammatory diseases (multiple sclerosis, immune-mediated neuropathies). When specific channels are affected, axonal/neuronal excitability primarily alters according to original function of the corresponding channels. Separately, in the 1990s, axonal excitability testing was developed to assess ion channel function, membrane potential, and passive membrane properties non-invasively in human subjects. Using this technique, numerous papers on altered axonal excitability in a variety of disorders have been published since 2000. In a recent issue of Experimental Neurology, Park et al. demonstrated changes in peripheral axonal excitability in limbic encephalitis and acquired neuromyotonia with anti-voltage gated potassium channel antibodies. Unexpectedly, the results were not consistent with those caused by simple potassium channel blockade, suggesting that multiple other factors contribute to altered axonal excitability. In contrast it was reported that patients with episodic ataxia type 1 (genetic channelopathy with mutation of Kv1.1 channel gene) show prominent excitability changes exactly compatible with fast potassium channel blockade. This commentary aims to highlight findings of this study in a broader context, and provides possible explanations for the discrepancy of patterns of axonal excitability changes in acquired and genetic potassium channelopathies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Although autoantibodies targeted against voltage-gated potassium channel (VGKC)-associated proteins have been identified in limbic encephalitis (LE) and acquired neuromyotonia (aNMT), the role of these antibodies in disease pathophysiology has not been elucidated. The present study investigated axonal function across the spectrum of VGKC-complex antibody associated disorders., Methods: Peripheral axonal excitability studies were undertaken in a cohort of patients with LE (N=6) and aNMT (N=11), compared to healthy controls (HC; N=20)., Results: Patients with LE demonstrated prominent abnormalities in peripheral axonal excitability during the acute phase, with reduced threshold change in threshold electrotonus (depolarizing 10-20 LE: 58.5±3.1%; HC: 67.4±0.9%; P<.005; S2 accommodation LE: 17.2±1.4%; HC: 22.2±0.6%; P≤.005) and in recovery cycle parameters (superexcitability LE: -16.0±0.9%; HC: -23.4±1.1%; P<.01; subexcitability LE: 8.5±1.2%; HC: 13.8±0.7%; P≤.005). The pattern of change in LE patients was dissimilar to the effects of antiepileptic medications, suggesting that these factors did not underlie excitability changes in LE. Normalization of excitability parameters was associated with recovery (TEd peak correlation coefficient=.868; P=.002), suggesting that peripheral excitability studies may provide a marker associated with clinical improvement. In contrast, patients with aNMT demonstrated no significant changes at the site of stimulation., Conclusions: The lack of prominent excitability abnormalities in patients with aNMT likely reflects a distal origin of hyperexcitability, expected to be at the motor nerve terminal, while the prominent changes observed in patients with LE likely represent a complex disturbance at the level of the axonal membrane, combined with electrolyte imbalance and adaptive change., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2014.)

Background and Purpose: To conduct a retrospective study to investigate the causes of acquired superior oblique dysfunction, excluding paralysis, in a consecutive series of adult patients and to compare presenting symptoms and clinical findings., Methods: A retrospective review of all adult patients with superior oblique dysfunction between the ages of 18 and 80 who met the study profile was conducted at Saint Louis University Medical Center between January 2000 and April 2012. The presenting symptoms, clinical findings, and treatment course for each patient was recorded. The study was approved by the Institutional Review Board of our institution., Results: Acquired forms of nonparalytic superior oblique dysfunction were identified in forty-eight patients. These included superior oblique myokymia (twenty-three patients), superior oblique click syndrome or variable Brown syndrome (nine), canine tooth syndrome (five), spontaneous acquired Brown syndrome (four), iatrogenic or traumatic Brown syndrome (four), and ocular neuromyotonia affecting the superior oblique (three)., Conclusions: Several nonparalytic entities were identified that caused superior oblique dysfunction. Clinical findings may be similar despite entirely different mechanisms. Subjective symptoms may be difficult for the patient to describe or for the examiner to elicit on the day of the examination. Specific techniques can be used in eliciting, differentiating, and documenting the conditions. These included trochlear palpation, modified head tilt technique, interpretation of torsion, and Hess charts., (© 2014 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 64, 2014, ISSN 0065-955X, E-ISSN 1553-4448.)

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.

Background: To report an unusual case of cyclic oculomotor nerve paresis and spasms, which developed 5 years following brain radiotherapy for cerebellar medulloblastoma., Methods: Observational case report., Results: The cyclic oculomotor nerve paresis and spasms resolved in our patient when treated with carbamazepine. However, because of severe photophobia and tearing, carbamazepine had to be discontinued leading to reappearance of the eye movement disorder., Conclusion: Cyclic oculomotor nerve paresis and spasms appear to be a delayed effect of radiotherapy and respond to carbamazepine therapy. It may be a rare form of ocular neuromyotonia.

Ocular neuromyotonia is an episodic involuntary contraction of one or more of the extraocular muscles resulting from spontaneous neural discharges of the oculomotor nerve. It is characterized by symptomatic diplopia for the duration of the contraction and occurs either spontaneously or after a sustained eccentric gaze. Although the mechanism of ocular neuromyotonia is not fully understood, primary or secondary aberrant regeneration and consequent ephaptic transmission generally are held to be involved. We report the case of a patient with right oculomotor neuromyotonia accompanied by lid ptosis on abduction of the left eye who was successfully treated with oral carbamazepine., (Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

Thymoma-associated paraneoplastic diseases include myasthenia gravis (MG), neuromyotonia (NMT), Morvan's syndrome, and several non-neurological paraneoplastic manifestations, including glomerulonephritis. Paraneoplastic syndromes often precede the occurrence of thymoma, but cases occurring after thymomectomy, which sometimes herald the recurrence of thymoma, have also been described. We report on a patient who developed MG after thymomectomy for a malignant thymoma. After MG remission, NMT and Morvan's syndrome occurred, which heralded a mediastinic recurrence, as demonstrated only by autopsy findings.

Ocular neuromyotonia (ONM) is a rare neurogenic disorder of ocular motility. The affected patients complain of recurrent transient diplopia secondary to a sudden, painless deviation of one eye. This deviation occurs in the direction of action of an extraocular muscle, which is being stimulated at high frequency. ONM is usually seen after radiation therapy, but may also be caused by compression of the affected cranial nerve. The pathophysiology of ONM is incompletely 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 re-organisation. The diagnosis of ONM is made based on clinical findings and can be supported by electrophysiological characteristics. Neuroimaging with attention to the affected cranial nerve should be obtained in order to exclude a compressive cause. Therapy of ONM with carbamazepine is usually effective., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Three patients who underwent multiple intracranial operations for recurrent nonsecreting pituitary adenomas followed by gamma knife stereotactic radiosurgery developed diplopia at 1, 5, and 6 years after the treatments. Examination disclosed features of ocular neuromyotonia, a phenomenon attributed to radiation damage to ocular motor cranial nerves. Amply reported after external beam radiotherapy, neuromyotonia has not been described after radiosurgery previously. These patients are, however, exceptional in that all had undergone multiple sellar region operations or received high doses of radiotherapy, or both.

Ocular neuromyotonia is a rare disease that is diagnosed mainly in patients treated with radiation. All such patients described in the literature presented with temporary diplopic images as a common symptom. In our case, the patient described an abducens paresis of the right eye combined with a sporadic exotropia half a year after radiation treatment of an epipharynx carcinoma. An adduction deficit on the right side could be triggered by holding the gaze to the right over a longer period of time, leading to exotropia in the primary position and gaze to the left. Symptoms were reduced with carbamazepine.

Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia (Isaacs' syndrome) and related disorders such as Morvan's syndrome and some cases of limbic encephalitis. The mechanisms underlying the various phenotypes induced by VGKC-Abs are not fully understood. Recently, we reported a case of LE with VGKC-Abs accompanied by severe intestinal pseudo-obstruction and thymoma. Thymectomy and immunosuppressive therapy induced dramatic clinical improvement of LE symptoms, and VGKC-Abs titers decreased from 1254 pM to 549 pM (normal>100 pM). Seventeen months later, the patient developed progressive generalized muscle cramping, paresthesias in his lower extremities, excessive sweating, and severe constipation. There was no recurrence of the LE. Electromyography showed fasciculation potentials and myokymic discharges, and the plasma VGKC-Abs titer was again elevated to 879 pM. Here we report a case of Isaacs' syndrome after complete remission of LE with VGKC-Abs that may provide an insight into a possible link among VGKC-Abs associated syndromes.

A 15-year-old girl, previously treated with radiation, chemotherapy, and surgery for a posterior fossa medulloblastoma and parasellar metastasis at age 8, presented with a 10-month history of episodic horizontal diplopia. She was diagnosed with ocular neuromyotonia and successfully treated with oral carbamazepine. Given the strong association between peripheral neuromyotonia and the presence of autoimmune antivoltage-gated potassium channels, the patient's blood was tested and found negative for these autoantibodies. This is the first time this has been verified in a person with ocular neuromyotonia.

Ocular neuromyotonia refers to paroxysmal involuntary contraction of one or more ocular muscles resulting in paroxysmal diplopia and strabismus. A 73-year-old woman reported spells of horizontal diplopia that usually developed after leftward gaze and mostly lasted less than one minute. Between the episodes, the extraocular movements were normal without aberrant regeneration. The diplopic paroxysms could be triggered by leftward gaze for several seconds. During the episode, the left eye was exotropic with mild adduction limitation. Brain imaging revealed an aneurysm in the left internal carotid artery. The episodes resolved with carbamazepine. Aneurysm of the internal carotid artery is a rare cause of abducens neuromyotonia. A compressive lesion may give rise to ocular neuromyotonia even in the absence of prior irradiation.

Acquired neuromyotonia is defined as continuous muscle activity originated in peripheral nerve due to alterations of the motor axon membrane. It has been considered a paraneoplastic syndrome in patients with neoplasms of the immune system, mainly lymphomas. Similarly, involvement of the motor neuron has been described as an uncommon paraneoplastic complication, also in relationship to lymphomas. We report a rare case, given the presence of two uncommon paraneoplastic manifestations such as neuromyotonia and reversible paraneoplastic lower motor neuronopathy secondary to clear cell renal carcinoma.

Ocular neuromyotonia is an uncommon disorder resulting from episodic involuntary discharge of ocular motor nerves producing sustained contraction of their respective ocular muscles. Ocular neuromyotonia manifests in brief spells of diplopia occurring spontaneously or after eccentric gaze holding. In most cases, ocular neuromyotonia follows months or years after radiotherapy to the sellar and parasellar region and involves the oculomotor nerve. We report two unusual cases of abducens nerve ocular neuromyotonia that followed radiation therapy of tumors in areas other than the sellar or parasellar region.

We report a 52-year-old man with slowly progressive dysarthria and dysphagia for about 11 years after radiation therapy of nasopharyngeal carcinoma. Neurological examination revealed atrophy and myokymia on the left side of the tongue and in the left mentalis muscles. Electrical discharges of myokymia and neuromyotonia were also observed in the aforementioned muscles, suggesting increased motor axonal membrane excitability involving the left hypoglossal nerve and the marginal mendibular branch of the left facial nerve. Magnetic resonance imaging of the brain did not show any evidence of tumor recurrence, indicating that irradiation probably plays an important role in pathogenesis. Focal myokymia with concomitant neuromyotonia in unilateral tongue and mentalis muscles could be an unusual delayed manifestation after radiation therapy.

We report a patient with Isaacs' syndrome associated with myasthenia gravis and pleural recurrence of thymoma, who showed severe limb pain attributed to hyperexcitability of sensory nerves. Myokymia and severe pain were successfully treated with cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy, but neither pharmacotherapy nor plasma exchange showed obvious clinical effects. Pleural thymoma in our patient may have caused Isaacs' syndrome, probably by unconfirmed humoral immune mechanisms. Cytoreductive treatment for recurrent thymoma should be actively considered as a potent therapeutic option in refractory patients with disabling neuromyotonia symptoms.

Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs) directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG) is due, in most cases, to abs against the nicotinic acetylcholine receptor (AChR). Anti-AChR-positive MG actually includes different disease entities: weakness can be confined to extrinsic ocular muscles or can be generalized; patients with generalized MG (G-MG) can be subdivided on the basis of age of onset, HLA association and thymic pathology. About 15% of G-MG patients are anti-AChR-negative; in a proportion of these cases serum abs against the muscle- specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by predominant involvement of bulbar muscles and very low frequency of thymic pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle weakness and autonomic disturbances and it is paraneoplastic in over 50% of the cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be due to anti-voltage-gated potassium channel abs, signs of peripheral nerve hyperexcitability can be associated with CNS features.