Neuro-Behçe Disease Causing Nuclear/Fascicular Forth Nerve Palsy

Neuro-Behçe disease (NBD) has a predilection for affecting the parenchyma of the upper brainstem; however, involvement of the fourth nerve nucleus or fascicle by NBD has not been previously described. We report a case of a young man with acute right fourth nerve palsy and history of Behçet disease with an enhancing lesion in the left caudal midbrain corresponding to the left trochlear nerve nucleus/fascicle. This is the first described case of NBD producing nuclear/fascicular fourth nerve palsy. It also demonstrates an important clinicoanatomical correlate of decussation of fourth nerve fibers to the opposite side after exiting the midbrain.

Photo and Video Essay Section Editors: Melissa W. Ko, Dean M. Cestari, Peter Quiros, Kimberly M. Winges, MD MD MD MD Neuro-Behçe Disease Causing Nuclear/Fascicular Forth Nerve Palsy Eli Kisilevsky, MD, Edward A. Margolin, MD FIG. 1. The cardinal positions of gaze revealed a right hypertropia (RHT) that increased with left gaze. The Parks-Bielschowsky 3-step test revealed worsening of hypertropia on right head tilt. Abstract: Neuro-Behçe disease (NBD) has a predilection for affecting the parenchyma of the upper brainstem; however, involvement of the fourth nerve nucleus or fascicle by NBD has not been previously described. We report a case of a young man with acute right fourth nerve palsy and history of Behçet disease with an enhancing lesion in the left caudal midbrain corresponding to the left trochlear nerve nucleus/ fascicle. This is the first described case of NBD producing nuclear/fascicular fourth nerve palsy. It also demonstrates an important clinicoanatomical correlate of decussation of fourth nerve fibers to the opposite side after exiting the midbrain. Journal of Neuro-Ophthalmology 2022;42:e517–e519 doi: 10.1097/WNO.0000000000001402 © 2021 by North American Neuro-Ophthalmology Society A Address correspondence to Edward A. Margolin, MD, Department of Ophthalmology and Vision Sciences, University of Toronto, 801 Eglinton Avenue W. Suite 301. Toronto, ON, Canada M5N1E3; E-mail: [e-mail] 25 year-old man presented with acute onset of binocular vertical diplopia for the last 3 days. He had a history of Behçet disease (BD) diagnosed 3 years ago, which was controlled with azathioprine. He also endorsed a history of new-onset headaches. On examination, visual acuity was 20/20 in both eyes, pupils were equal, reactive to light, without a relative afferent pupillary defect. Posterior pole examination was normal. There was no ptosis, and extraocular motility was full with normal smooth pursuit and saccades and no nystagmus. Examination of ocular alignment with alternate cover testing revealed right hypertropia of 8 prism diopters (PD) in primary gaze, which increased on looking to the left (10 PD) and on tilting the head to the Kisilevsky and Margolin: J Neuro-Ophthalmol 2022; 42: e517-e519 e517 Department of Ophthalmology and Vision Sciences (EK, EAM), University of Toronto, Toronto, Canada; Department of Ophthalmology (EAM), Toronto Western Hospital, University Health Network, Toronto, Canada; and Department of Ophthalmology (EAM), Mount Sinai Hospital, Sinai Health System, Toronto, Canada. 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). Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay FIG. 2. T2 weighted contrast enhanced axial image through caudal midbrain demonstrating a slightly enhancing lesion within left mid brain crossing the midline and extending into superior cerebellar peduncle. Behcet’s disease (1,2). There are no clinical tests to define the diagnosis, but HLA-B51 and pathergy in conjunction with thorough physical examination can aid in diagnosis. Neuro-Behçet disease (NBD) is considered in any patient diagnosed with definite BD demonstrating neurological signs or symptoms. NBD is rare and is present in only 9% of patients with BD (3). It typically follows other symptoms of BD, but in rare cases, neurological manifestations can precede ophthalmologic or mucocutaneous involvement (4). NBD affects men 2.8 times more commonly than women (5). The manifestations of NBD are divided into parenchymal and nonparencyhmal involvement and are identified based on common presentations. Nonparenchymal involvement refers to venous involvement producing cerebral venous sinus thrombosis (CVST) or arterial involvement causing stenosis, aneurysm formation, or cervicocephalic arterial dissection (5). Parenchymal and nonparenchymal involvement rarely occurs in the same patient (5). Parencyhmal involvement typically affects the brainstem, causing ophthalmoplegia, cerebellar ataxia, hearing loss, and/or facial palsy. One study found that 13% of patients with NBD presented with neuroophthalmological symptoms, including papilledema, papillitis, retrobulbar optic neuritis, and third and sixth cranial nerve palsies (6). Involvement of the cortex, the spine, or the peripheral nervous system is not as common. Patients present with variable sensorimotor signs, movement disorders, seizures, psychiatric manifestations, and acute confusion state. The diagnosis of NBD can be made in any patient with BD but thorough investigations tailored to the presentation should be considered to rule out other potential etiologies. Treatment of BD should be a multidisciplinary approach tailored to the multiorgan manifestations of BD. Corticosteroids therapy remains the mainstay of therapy for acute control of inflammatory manifestations. Steroid-sparing treatment, including colchicine, azathioprine, cyclosporine, and newer biologics such as TNF-inhibitors and interferon alpha agents, can provide long-term control of BD manifestations (7). A nuclear-fascicular trochlear nerve palsy due to NBD was not described in the literature previously. Fourth (trochlear) cranial nerve palsy is the most common cause of acquired vertical diplopia and strabismus. Common causes for acquired fourth nerve palsy include trauma, demyelination, microischemia, infarction, neuro-inflammatory disease, and neoplasms. The trochlear nucleus is located in the dorsal midbrain at the level of the inferior colliculus. Medial longitudinal fasciculus, the oculosympathetic pathways, and the vestibulocular pathways are all located in close proximity to the fourth nerve nucleus. Thus, lesions affecting the fourth nerve nucleus/ fascicle can also affect these structure, producing contralateral internuclear ophthalmoplegia, contralateral Horner syndrome, or skew deviation, respectively (8,9). Our patient did not demonstrate any findings consistent with these syndromes. In summary, patients with known BD can present with cranial nerve palsies due to the disease’s predilection to the e518 Kisilevsky and Margolin: J Neuro-Ophthalmol 2022; 42: e517-e519 right (14 PD) and better when looking to the right (6 PD) and tilting the head to the left (4 PD), thus fitting the Parks–Bielschowsky 3-step test for right fourth cranial nerve palsy (Fig. 1 and See Supplemental Digital Content, Video, http://links.lww.com/WNO/A511). Double Maddox rod testing revealed 5 degrees of right excyclotorsion consistent with right fourth nerve palsy. The rest of the cranial nerve examination was normal. Muscle tone, reflexes, and power were normal in all 4 limbs, and sensory and cerebellar examination did not reveal any abnormalities. As the patient had a preexisting diagnosis of BD, it was postulated that his new right fourth nerve palsy could be central in etiology because BD has a predilection for affecting the midbrain. Either the nucleus or the fascicle of the fourth nerve could be affected because after traveling a short course through the dorsocaudal midbrain, fourth nerve fibers cross to the opposite site; thus, the lesion that affecting the nucleus and/or fascicle of the fourth nerve in the midbrain will clinically produce fourth nerve palsy on the contralateral side. Thus, this patient’s right cranial nerve 4 palsy likely localizes to the lesion affecting the left nucleus and/or fascicle of the fourth nerve in the midbrain. Brain MRI was performed and revealed an enhancing lesions in the left midbrain and superior cerebellar peduncle as predicted by the clinical examination (Fig. 2). BD is a multisystemic inflammatory disease of unknown origin. It is characterized by oral and genital ulcers and uveitis, first described in 1937. The diagnosis is made by fulfilling diagnostic criteria set by the International Study Group for Behcet’s disease or the International Criteria for Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay upper brainstem. When fourth nerve palsy is detected in a patient with BD, a lesion in the contralateral dorsal midbrain should be suspected because of the immediate decussation of fourth nerve fascicles to the opposite site within the midbrain. 3. 4. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. A. Margolin, and E. Kisilevsky; b. Acquisition of data: E. A. Margolin and E. Kisilevsky; c. Analysis and interpretation of data: E. A. Margolin, and E. Kisilevsky. Category 2: a. Drafting the manuscript: E. A. Margolin and E. Kisilevsky; b. Revising it for intellectual content: E. A. Margolin and E. Kisilevsky. Category 3: a. Final approval of the completed manuscript: E. A. Margolin and E. 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