Paroxysmal Adduction After Internuclear Ophthalmoplegia

Paroxysmal symptoms in multiple sclerosis (MS) consist of brief, stereotyped, self-limited, and predominantly positive focal neurological symptoms (1,2). Examination between attacks can be unremarkable, and hence, they often constitute a diagnostic challenge. Ocular motor paroxysms in MS have been anecdotally reported, and the majority lacks anatomical correlation and quantitative assessment(1,2). We provide detailed ocular motor analysis in a MS patient with paroxysmal monocular adduction, occurring several years after an episode of bilateral internuclear ophthalmoplegia (INO), and associated with a chronic para-median dorsal pontine demyelinating plaque.

Clinical Correspondence Paroxysmal Adduction After Internuclear Ophthalmoplegia Bruno Miranda, MD, Ana I. Martins, MD, André F. Jorge, MD, César Nunes, MD, Lívia Sousa, MD, João Lemos, MD, PhD P aroxysmal symptoms in multiple sclerosis (MS) consist of brief, stereotyped, self-limited, and predominantly positive focal neurological symptoms (1,2). Examination between attacks can be unremarkable, and hence, they often constitute a diagnostic challenge. Ocular motor paroxysms in MS have been anecdotally reported, and the majority lacks anatomical correlation and quantitative assessment (1,2). We provide detailed ocular motor analysis in a MS patient with paroxysmal monocular adduction, occurring several years after an episode of bilateral internuclear ophthalmoplegia (INO), and associated with a chronic paramedian dorsal pontine demyelinating plaque. A 57-year-old man with relapsing-remitting MS for 16 years presented with a 4-year history of recurrent shortlasting episodes of binocular horizontal diplopia in straight gaze lasting a few seconds and occurring up to 100 times per day. Exercise, heat, hyperventilation, and touch or movement of the eyes/head/limbs had no precipitating effect. The patient was asymptomatic between events. His MS history was remarkable for an episode of bilateral INO 14 years earlier, of which he had subjectively recovered after 1 month (i.e., no diplopia), albeit residual bilateral adduction weakness persisted over the years. Current neuroophthalmological examination showed best-corrected visual acuity of 20/20 in both eyes; color vision was 17/17 in the right eye and 15/17 in the left eye on Ishihara color plates; there was a left relative afferent pupillary defect, and the left optic disc was pale. Alternate cover testing showed a 4-prism diopter esotropia in straight gaze. Quantitative ocular-motor Department of Neurosciences and Mental Health (BM), Santa Maria Hospital, Lisbon, Portugal; Faculty of Medicine (BM), University of Lisbon, Lisbon, Portugal; Neurology Department (AIM, AFJ, LS, JL), Coimbra University Hospital Centre, Coimbra, Portugal; Neuroradiology Department (CN), Coimbra University Hospital Centre, Coimbra, Portugal; and Faculty of Medicine (LS, JL), University of Coimbra, Coimbra, Portugal. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). B. Miranda and A. I. Martins contributed equally to the article. L. Sousa and J. Lemos shared senior co-authorship. Address correspondence to João Lemos, MD, PhD, Neurology Department, Coimbra University Hospital Centre, Praceta Professor Mota Pinto, Coimbra 3000-075, Portugal; E-mail: [e-mail] 250 analysis with infrared binocular video-oculography (VO425; Interacoustics, Assen, Denmark; 105 Hz) was performed between and during the diplopia attacks. Between attacks, while fixating a 0.8° central target at a 90-cm distance, there was upbeat nystagmus (mean slow phase velocity, 8°/s) in straight gaze. During 5-30° horizontal saccades, there was bilateral slowing of adducting saccades (mean velocity, 143°/s right-eye, 156°/s left-eye) and abducting nystagmus, consistent with bilateral INO. During an attack, while fixating the central target, apart from continuous upbeat nystagmus, there was intermittent adduction of the left eye lasting w5 seconds at a frequency of 0.05 Hz (Fig. 1 and see Supplemental Digital Content, Video, http://links. lww.com/WNO/A382), with no simultaneous change in pupils' size, and consistently manifesting as transient diplopia. Brain MRI showed a nonenhancing hyperintense lesion in the paramedian dorsal pons affecting both medial longitudinal fasciculi (MLF), more prominent on the left, already observed in older scans (Fig. 1, middle segment). Other supra- and infratentorial nonenhancing lesions were present, apparently not involving oculomotor- and/or vision-related circuitries. The patient was diagnosed with paroxysmal adduction of the left eye and started carbamazepine 100 mg twice daily, showing complete resolution of the symptoms (Fig. 1 and Supplemental Digital Content, Video, http://links.lww.com/WNO/A382). Ocular-motor paroxysms in MS have been poorly described and are usually observed in association with other symptoms, including dysarthria and ataxia (1,2). Previous ocular-motor paroxysms described up to date in MS include monocular adduction with head turn, superior rectus and levator palpebra spasm, ocular tilt reaction, ocular flutter, and convergence spasm (1-3). In the case previous to ours describing paroxysmal monocular adduction, objective documentation of the paroxysm was not provided and neuroimaging correlation was lacking (1). Here, we provide videooculographic evidence of the intermittent left eye adduction in the presence of a chronic MLF lesion. Paroxysmal symptoms in MS seem to be either generated by spontaneous ectopic intralesional discharges after an increment of sodium channels after demyelination or by transversely spreading ephatic activation of axons originating from a demyelinated lesion (2,4,5). In our case, the absence of triggering stimuli eliciting the attacks made ephatic mechanisms less likely. On Miranda et al: J Neuro-Ophthalmol 2020; 40: 250-251 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Video-oculography and MRI. Binocular eye movement tracings during a paroxysmal episode showed intermittent adduction movements of the left eye (upward deflections) lasting w5 seconds (note the inward deviation of the left eye during a paroxysm-the light reflex is temporal to the center of the left pupil) (top segment). Axial fluidattenuated inversion recovery (FLAIR) sequence revealed, among other demyelinating lesions, a chronic hyperintense lesion in the paramedian dorsal pontine tegmentum area (arrow), involving both MLF, slightly more pronounced on the left (middle segment). After treatment, intermittent deviation of the left eye fully ceased (bottom segment). In the eye movement tracings, upward deflections correspond to rightward movements, whereas downward deflections correspond to leftward movements.OD, right eye; OS, left eye. the other hand, the possibility of ectopic discharges arising from the chronic MLF lesion was further supported by the prompt clinical response to carbamazepine, which acts by inhibiting repetitive discharges through effects on sodium channel conduction. The demyelinating lesion involving both MLFs evidenced in imaging was more prominent in the left side. This asymmetry might explain the exclusively left-sided paroxysmal adduction, which may reflect a transient activation of left ascending MLF axons, causing excitation of the medial rectus subnucleus and subsequent contraction of the left medial rectus muscle. In contrast with Uhthoff's phenomenon-related episodes in MS, which seem to reflect the precipitation of nerve conduction slowing and block by an increase in core body temperature within predisposed demyelinated fibers (potentially worsening a pre-existent Miranda et al: J Neuro-Ophthalmol 2020; 40: 250-251 INO, by slowing/impairing adduction even more), paroxysmal events are believed to be associated with an opposite phenomenon, that is, abnormal excitation of demyelinated fibers due to extranodal depolarization, mechanosensitivity, and/or exposure and activation of axonal channels (which, in our case, may have led to spontaneous MLF excitation and consequent adduction of the ipsilateral eye, transiently "reverting" the impaired adduction status of a pre-existent INO) (5). Importantly, paroxysmal events in MS seem to require the contribution of several additional factors apart from demyelination to occur (i.e., extranodal depolarization, mechanosensitivity, and/or exposure and activation of axonal channels), which might explain their relatively low frequency (1-3). Although there were additional infratentorial demyelinating lesions identified in the MRI, none of these seemed to explain the patient's symptoms. Given that the episodes were not precipitated by sustained eccentric gaze, the possibility of neuromyotonia was less likely. Similarly, the absence of variation in pupils' size during the episodes made convergence spasm equally unlikely. Ocular-motor paroxysms in MS may sometimes be overlooked or confused with clinical relapses (e.g., mild INO or sixth nerve palsy). Therefore, their early detection, ideally with the use of quantitative ocular motor analysis, is crucial to initiate the appropriate treatment. Our case constitutes a unique report of paroxysmal monocular adduction after INO in MS. Moreover, we provide evidence of its possible anatomical correlate, namely a chronic demyelinating lesion in the MLF, which over time, might have become prone to pathological axonal discharge. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. Miranda, A. I. Martins, L. Sousa, and J. Lemos; b. Acquisition of data: B. Miranda, A. I. Martins, A. F. Jorge, C. Nunes, and J. Lemos; c. Analysis and interpretation of data: B. Miranda, A. I. Martins, A. F. Jorge, C. Nunes, L. Sousa, and J. Lemos. Category 2: a. Drafting the manuscript: B. Miranda, A. I. Martins, and J. Lemos; b. Revising it for intellectual content: C. Nunes, L. Sousa, and J. Lemos; Category 3: a. Final approval of the completed manuscript: B. Miranda, A. I. Martins, A. F. Jorge, C. Nunes, L. Sousa, and J. Lemos. REFERENCES 1. Matthews WB. Paroxysmal symptoms in multiple sclerosis. 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