Journal of Neuro-Ophthalmology, June 2009, Volume 29, Issue 2

Ocular neuromyotonia after gamma knife stereotactic radiation therapy.

ORIGINAL CONTRIBUTION Ocular Neuromyotonia After Gamma Knife Stereotactic Radiation Therapy Jason W. Much, MD, Eric D. Weber, MD, and Steven A. Newman, MD Abstract: 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 phe-nomenon attributed to radiation damage to ocular motor cranial nerves. Amply reported after external beam radiotherapy, neuromyotonia has not been described after radiosurgery previously. These pa-tients are, however, exceptional in that all had undergone multiple sellar region operations or received high doses of radiotherapy, or both. (J Neuro-Ophthalmol 2009;29:136-139) Ocular neuromyotonia is a paroxysmal misalignment of the eyes due to spontaneous repetitive firing of the third, sixth, or, less commonly, fourth cranial nerve. The characteristic clinical finding is an intermittent, incomitant misalignment lasting seconds to minutes that is often evoked by eccentric gaze. The pathogenesis involves primary tonic overaction of an extraocular muscle with impaired relaxation in a self-perpetuating cycle. Proposed mechanisms include ephaptic neural transmission, central synapse reorganization, and axonal hyperexcitability due to potassium channel dysfunction. Approximately 40 cases have been reported (1-6), more than half after external beam radiation to the sellar or parasellar area with a latency of onset varying between 2 months and 18 years (1,8). Some authors have suggested a link between neuromyo-tonia and aberrant regeneration of a partially damaged cranial nerve (8). Department of Ophthalmology, University of Virginia, Charlottesville, Virginia. This work was presented in part at the North American Neuro- Ophthalmology Society Annual Meeting, March 2008, Orlando, FL. Address correspondence to Jason W. Much, MD, Department of Ophthalmology, University of Virginia, PO Box 800715, Charlottesville, VA 22908; E-mail: [e-mail] No cases of ocular neuromyotonia have been reported after gamma knife stereotactic radiosurgery, a newer, minimally invasive treatment designed to deliver a single focused dose of intracranial radiation while sparing sur-rounding tissues. We report three cases of ocular neuro-myotonia after gamma knife stereotactic radiation therapy for residual pituitary tumors. CASE REPORTS Case 1 A 36-year-old woman with Cushing disease under-went subtotal transsphenoidal pituitary surgery because of persistent endocrine abnormalities. The following year she received 22-Gy gamma knife radiation for residual tumor close to the left optic nerve. Because hormone levels remained abnormally high after this treatment, she underwent an additional 35.7-Gy gamma knife treatment 1 year later. Six years later, she developed diplopia and received a diagnosis of a left third cranial nerve palsy elsewhere. Because of the imaging disclosure of recurrent tumor, she underwent a second transsphenoidal operation. Several weeks after surgery, she complained that her left eye ‘‘would get stuck sometimes.'' On our examination, she displayed mildly reduced abduction of the left eye with sustained abduction after prolonged left gaze (Fig. 1). We made a diagnosis of partial left sixth cranial nerve palsy with ocular neuromyotonia and started therapy with 100 mg carbamazepine 3 times daily. On follow-up examination 6 months after starting carbamazepine treatment, she stated that the eye had stopped ‘‘getting stuck'' 1 week after starting the drug. She reported no side effects. No ocular myotonia could be elicited on examination. She continued the carbamazepine at the same dose. Case 2 A 27-year-old woman presented to her ophthalmol-ogist complaining of blurred vision in the left eye. Brain MRI revealed an extensive sellar mass. She underwent subtotal resection of a nonsecreting pituitary adenoma via 136 J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Ocular Neuromyotonia J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 FIG. 1. Case 1. A. A partial supraduction deficit is present in the left eye. B. The patient looks straight ahead after a period of left gaze. The left eye is exodeviated, consistent with neuromyotonia of the left sixth cranial nerve. craniotomy and subsequently developed double vision. Six months later, a transsphenoidal resection was performed for residual tumor, but the diplopia persisted, and she was referred to us for evaluation. On our examination 4 months after the trans-sphenoidal surgery, she had a right sixth cranial nerve palsy and a subtle left optic neuropathy. Three months after this visit, she received 50-Gy gamma knife radiation for residual tumor. About 1 year after the gamma knife treatment, she complained of intermittent diplopia and reported that her right eye would ‘‘lock in'' when she looked leftward. Our examination showed persistent exodeviation after pro-longed right lateral gaze (Fig. 2). We diagnosed ocular neuromyotonia of the right sixth cranial nerve and treated her with 100 mg carbamazepine 3 times daily. She discontinued the carbamazepine after 1 month because she did not think it was helping. We suggested an increased dose, but she declined it. She used no medication for the neuromyotonia. At a follow-up examination 3 months later, she reported decreased frequency of the eye ‘‘sticking,'' and we found no evidence of ocular neuromyotonia. Case 3 A 35-year-old woman had undergone two trans-sphenoidal resections and a craniotomy for a large, recur-rent nonsecreting pituitary macroadenoma with growth into the left cavernous sinus. Two years after the craniotomy, she had received 58 Gy of external beam x-ray therapy, followed by 16-Gy gamma knife radiation 2 years later. One year after the gamma knife treatment, she received the diagnosis elsewhere of an incomplete left third cranial nerve palsy with aberrant regeneration, which had been stable for more than 2 years until she began to notice worsening of diplopia. She underwent a lateral rectus recession and medial rectus resection on the left eye for 137 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 Much et al FIG. 2. Case 2. A. A subtle right abduction deficit is present, consistent with a right sixth cranial nerve palsy. B. The patient attempts left gaze after a period of right gaze. The right eye does not adduct, consistent with neuromyotonia of the right sixth cranial nerve. exotropia. One year after the eye muscle surgery, she began to complain of her left eye ‘‘sticking in.'' On our examination, she demonstrated an exodevia-tion that changed to a transient esodeviation after sustained right gaze. We diagnosed ocular neuromyotonia of the left third cranial nerve and treated her with 100 mg carbamazepine 3 times daily, the patient stated that her symptoms of ‘‘eye sticking'' had improved. In a telephone follow-up 1 year later, she reported that she had stopped using the carbamazepine because it ‘‘made my left eyelid droop more.'' Although the drug relieved her myotonia, ‘‘the side effect was worse.'' DISCUSSION We have reported three patients who developed ocular neuromyotonia at 1 year (Case 2), 5 years (Case 3), and 6 years (Case 1) after gamma knife stereotactic radiosurgery to the sellar/cavernous sinus region. Although ocular neuromyotonia has been amply reported after external beam irradiation (1-6), it has not been described after stereotactic gamma knife radiotherapy, which delivers a more precise, targeted dose of radiation over a single session. Admittedly, our patients are exceptional in that all required multiple sellar region operations and received either multiple doses of stereotactic radiosurgery (Case 1) or stereotactic and external beam radiation treatments for recurrent tumor (Case 3). We present these patients to emphasize that neuro-myotonia can occur after radiosurgery and that its clinical manifestations may be mistakenly attributed to cranial nerve palsy caused by recurrent tumor. Previous reports have established that ocular neuromyotonia is clearly a form of radiation-induced ocular motor cranial neurop-athy (1-6). The standard treatment of ocular neuromyotonia has been oral carbamazepine, an agent known to reduce 138 © 2009 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Ocular Neuromyotonia J Neuro-Ophthalmol, Vol. 29, No. 2, 2009 neuronal and axonal excitability (9,10). Its efficacy in this condition is based purely on anecdote. Our experience with these patients does not allow us to be certain that it worked, and 2 of our patients discontinued its use because of perceived lack of benefit (Case 2) or side effects (Case 3). REFERENCES 1. Ela-Dalman N, Arnold AC, Chang LK, et al. Abducens nerve ocular neuromyotonia following non-sellar or parasellar tumors. Strabismus 2007;15:149-51. 2. Ezra E, Spalton D, Sanders MD, et al. Ocular neuromyotonia. Br J Ophthalmol 1996;80:350-5. 3. Fricke J, Neugebauer A, Kirsch A, et al. Ocular neuromyotonia: a case report. Strabismus 2002;10:119-24. 4. Frohman EM, Zee DS. Ocular neuromyotonia: clinical features, physiological mechanisms, and response to therapy. Ann Neurol 1995;37:620-6. 5. Newman SA. Gaze-induced strabismus. Surv Ophthalmol 1993;38: 303-9. 6. Yee RD, Purvin VA. Ocular neuromyotonia: three case reports with eye movement recordings. J Neuroophthalmol 1998;18:1-8. 7. Haupert CL, Newman NJ. Ocular neuromyotonia 18 years after radiation therapy. Arch Ophthalmol 1997;115:1331-2. 8. Choi KD, Hwang JM, Park SH, et al. Primary aberrant regeneration and neuromyotonia of the third cranial nerve. J Neuroophthalmol 2006;26:248-50. 9. Tilikete C, Vial C, Niederlaender M, et al. Idiopathic ocular neuromyotonia: a neurovascular compression syndrome? J Neurol Neurosurg Psychiatry 2000;69:642-4. 10. Neuropharmacology of the antiepileptic drugs. In: Goetz CG, ed. Textbook of Clinical Neurology. St. Louis: WB Saunders; 2007: 1235-9. 139 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.