Childhood onset of acquired neuromyotonia: association with vitamin D deficiency.

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.

Bilateral oculomotor ocular neuromyotonia: a case report.

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.

A novel association of ocular neuromyotonia with brainstem demyelination: two case reports.

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.

Ocular neuromyotonia: an unusual case after radiotheraphy for nasopharyngeal carcinoma.

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.

Partial third nerve palsy and ocular neuromyotonia from displacement of posterior communicating artery detected by high-resolution MRI.

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.

Acquired oculomotor nerve paresis with cyclic spasms in a young woman, a rare subtype of neuromyotonia.

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.

Novel case of ocular neuromyotonia associated with thyroid-related orbitopathy and literature review.

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.

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies.

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.

Thyroid peroxidase antibodies may induce demyelination and oculomotor neuromyotonia in the absence of thyroid eye disease.

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.

Post-surgical left oculomotor nerve neuromyotonia: Cause or coincidence?

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.

Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

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.].

Abducens neuromyotonia as the presenting sign of an intracranial tumor.

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.

Mercury poisoning complicated by acquired neuromyotonia syndrome: A case report.

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.

Multiple paraneoplastic diseases occurring in the same patient after thymomectomy.

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 after gamma knife stereotactic radiation therapy.

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.