Autoimmune Encephalitis Causing Supranuclear Ophthalmoparesis and Lateral Gaze Palsy

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Autoimmune Encephalitis Causing Supranuclear Ophthalmoparesis and Lateral Gaze Palsy Mohamed T. Shabana, MD, Deborah I. Friedman, MD, MPH A cinic cell carcinoma makes up 10%–15% of primary salivary gland tumors, and most commonly arises in the parotid gland (1). Although paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone have been reported, central nervous deficits related to a paraneoplastic etiology remain to be documented in acinic cell carcinoma (2). There is one reported case of ophthalmoplegia in acinic cell parotid cancer secondary to metastatic extension into the cavernous sinus (3). We report a case of cerebellar ataxia, ophthalmoplegia, supranuclear palsy, and autonomic dysfunction in a patient with acinic cell parotid cancer and autoimmune encephalitis. mologist and determined to have no visual impairment. He later required an indwelling urinary catheter because of increased difficulty voiding. His symptoms continued to evolve with difficulty looking to the left or right on both sides. He was readmitted to an outside hospital, diagnosed with Miller Fisher variant of Guillain–Barre syndrome and received a 5-day course of intravenous immunoglobulin (IVIG). The patient’s sister noted remarkable improvement in the patient’s gait. At the time of discharge, he was able to walk with an assistive device. He was sent to rehab, but further declined after a month after IVIG was completed. CASE PRESENTATION Evaluation at our hospital showed lack of volitional horizontal gaze with minimal ocular excursion with volitional up gaze and normal down gaze. There was disorientation, bilateral ptosis, dysarthria, dysmetria on finger to nose testing (left . right), and ataxia with spontaneous retropulsion. Strength, sensation, and reflexes were normal. Computed tomography of the chest, abdomen, and pelvis were negative. A left parotid mass was incidentally found on brain MRI with evidence of brainstem involvement (Fig. 1). A dedicated neck MRI showed a 2.2-cm enhancing parotid mass (Fig. 2). An ultrasound guided biopsy of the mass was scheduled as an outpatient. Serum antibody testing of GQ1B IgG, acetylcholine receptor, muscle-specific kinase, thyroid peroxidase, ganglioside panel, and autoimmune paraneoplastic panel were negative. Autoimmune encephalopathy panel was positive for GAD Ab with a titer of 0.11 nmol/L. Given the low titer, GAD Ab was believed to be suggestive of an autoimmune process, but unlikely to be contributing to the patient’s symptoms. Lumbar puncture demonstrated 9 nucleated cells/mm3, protein 48 mg/dL, glucose 65 mg/dL and RBC 27/mm3. Oligoclonal bands were not obtained. CSF was negative for anti-Ma1, antiMa2, anti-dipeptidyl-peptidase-like protein 6, 14-3-3, RTQUIC, and paraneoplastic panel. No testing looking for antibodies against the tumor was completed. He received 5 sessions of plasma exchange followed by IVIG 2 g/kg over 5 days with no clinical improvement. He was discharged to a skilled nursing facility. A week later, he was readmitted to for increased somnolence, and hypotension with systolic blood pressure in 80 seconds related to dehydration. Examination showed A 71-year-old man with a past medical history of hypertension, coronary artery disease, benign prostatic hyperplasia, and hypothyroidism initially developed difficulty sleeping and vivid nightmares 11 months before presentation. An outside sleep study showed sleep apnea, but his symptoms persisted despite using a continuous positive airway pressure therapy. Over the next 9 months, his symptoms progressed with difficulty tracking a tennis ball, imbalance, difficulty concentrating, constipation, difficulty voiding, short-term memory impairment, and self-reported weakness in his hands and legs. He denied leg stiffness, numbness, sensory changes, or tremulousness. He was admitted to an outside hospital after falling and hitting his head. During his initial examination, he was observed to have bilateral ptosis, difficulty chewing, weight loss, and hypersomnia described as falling asleep mid conversation. He was diagnosed with myasthenia gravis despite normal electrodiagnostic studies and discharged on pyridostigmine. His symptoms progressed with development of visual hallucinations. Pyridostigmine was discontinued because of lack of response. He was evaluated by an outside ophthalDepartments of Neurology (MS, DIF) and Ophthalmology (DIF), University of Texas Southwestern, Dallas, Texas. The authors report no conflicts of interest. Author contribution: Collection of data, drafting manuscript, analysis of data: M. Shabana; Drafting & revising manuscript, analysis of data: D. Friedman. Address correspondence to Mohamed Shabana, MD, 5323 Harry Hines Blvd G2.222, Dallas, TX 75390-9322, Mohamed.Shabana@ phhs.org e502 EVALUATION Shabana and Friedman: J Neuro-Ophthalmol 2022; 42: e502-e504 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Postcontrast T1 MR neck w/ & w/o contrast enhancing 2.2-cm mass in the left parotid gland (white arrow). parotidectomy confirmed a diagnosis of acinic cell carcinoma with high grade transformation. After resection and radiation therapy, his symptoms continued to improve with near return to baseline while maintaining oral steroids. He had a relapse 6 months later with a right gaze palsy. A repeat brain MRI with contrast was normal and he responded to a 5 days course of 1 g of IVMP. Two years later, he is well and in remission. DISCUSSION FIG. 1. T2 flair and postcontrast T1 images of MRI brain w/ & w/o contrast demonstrating no abnormal lesions or enhancement seen in the brainstem. hypersomnolence, absent volitional horizontal eye movements, marked limitation of vertical gaze, and a right hypertropia. Horizontal and vertical eye movements were full with oculocephalic maneuver. There was bilateral ptosis and right upper extremity dysmetria. A 24-hour EEG captured one right temporal electrographic seizure consistent associated lip smacking with generalized background delta slowing. Fine needle aspiration of the parotid mass showed high grade carcinoma. He received levetiracetam 3 g IV followed by 500 mg, which markedly improved his alertness, and intravenous methylprednisolone (IVMP) 1 g daily for 5 days with significant improvement in symptoms. At the time of discharge, he was able to ambulate with physical therapy, with improvement of his ptosis, bilateral ophthalmoplegia, cognition, and level of alertness. He was discharged on 60 mg oral prednisone daily. A biopsy and Shabana and Friedman: J Neuro-Ophthalmol 2022; 42: e502-e504 Autoimmune encephalitis is a clinical diagnosis and should be considered in patients with development of subacute neurologic symptoms. The absence of autoantibodies does not exclude the possibility that the disorder is immunemediated and the presence of antibodies does not always imply causation. (4). A thorough malignancy evaluation is necessary in all autoimmune encephalitis patients, particularly in the elderly. Supranuclear ophthalmoparesis and horizontal gaze palsy have not been previously described in autoimmune encephalitis secondary to parotid cancers. No structural lesion was detected to account for the patient’s neuro-ophthalmic findings. Although uncommon, parotid cancer should be considered in patients with a clinical diagnosis of autoimmune encephalopathy. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. Shabana; b. Acquisition of data: M. Shabana; c. Analysis and interpretation of data: M. Shabana and D. Friedman. Category 2: a. Drafting the manuscript: M. Shabana and D. Friedman; b. Revising it for intellectual content: M. Shabana and D. Friedman. Category 3: a. Final approval of the completed manuscript: M. Shabana and D. Friedman. REFERENCES 1. Patel NR, Sanghvi S, Khan MN, Husain Q, Baredes S, Eloy JA. Demographic trends and disease-specific survival in salivary acinic cell carcinoma: an analysis of 1129 cases. Laryngoscope. 2013;124:172–178. e503 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence 2. Castro OS, Sergio NJ, Souteiro P, Belo S, Oliveira AL, Neves C, Freitas P, Carvalho D. Acinic cell adenocarcinoma of the parotid gland associated with paraneoplastic Cushing’s syndrome - a rare clinical case. Endocrine Abstracts [online serial]. Bioscientifica. 2017;49:EP194. 3. Francis Thottian AG, Gandhi AK, Ramateke PP, Gogia A. Acinic cell carcinoma of parotid gland with cavernous sinus metastasis: a case report. J Can Res Ther. 2018;14:1428–1430. e504 4. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to the diagnosis of autoimmune encephalitis. Lancet. 2016;15:391–404. Shabana and Friedman: J Neuro-Ophthalmol 2022; 42: e502-e504 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.