Clues From Parinaud: Diagnostic Approaches in Neuro-Ophthalmology

Clinical Correspondence Clues From Parinaud: Diagnostic Approaches in NeuroOphthalmology Daniel N. de Souza, BS, Carter A. Bell, BA, Zachary P. Elkin, MD, Scott N. Grossman, MD A 53-year-old man presented to the emergency department (ED) of an outside hospital with complaints of dizziness, lightheadedness, bilateral ptosis, sense of near syncope, and diplopia with acute onset in the shower. Upon initial neurologic examination in the ED, he exhibited complete bilateral ophthalmoplegia with both eyes fixed in primary gaze, an inability to open both eyelids, symmetrically enlarged and unreactive pupils, and a progressive inability to respond to questions, increasing drowsiness, and slurred speech. This patient had a medical history of essential hypertension, glaucoma, and childhood exotropia status after 2 remote strabismus surgeries with bilateral 4-mm recession (weakening) of his lateral rectus muscles. A noncontrast head computerized tomography (CT) and an MRI of the brain with and without gadolinium were unrevealing during admission, as were acetylcholine receptor (AchR) antibody binding serologies. Given clinical concern for myasthenia gravis (MG), he was admitted and treated with 5 days of intravenous immunoglobulin (IVIg) and reported that he was progressively able to open his left eye again after the initial infusion. He was also prescribed mestinon (60 mg 3 times daily) and discharged home with outpatient followup. He followed up with a neurologist approximately 13 weeks after initial presentation, reporting that his ptosis had improved (greater improvement in left eye than the right), but that his diplopia remained persistent. On examination, he exhibited limited adduction, elevation, and depression in his right eye and limited elevation, depression, and a fatigable adduction deficit in his left eye. When the patient attempted vertical saccades toward up-gaze, he exhibited paradoxical convergence of the eyes with apparent retraction of the globes. An EMG-nerve conduction study (NCS) including peripheral limbs and single-fiber repetitive stimulation of the face and shoulder were completed during that visit and were negative. The patient was subsequently prescribed prednisone (up-titrating daily dosage by 10 mg weekly up to 50 mg) in an attempt to treat presumed autoimmune origin of symptoms. He also underwent further testing with a CT Departments of Neurology (DNdS, CAB, SNG) and Ophthalmology (ZPE), New York University Grossman School of Medicine, New York, New York. The authors report no conflicts of interest. Address correspondence to Scott N. Grossman, MD, NYU Grossman School of Medicine, 222 East 41st Street, 15th Floor, New York NY 10017; E-mail: [e-mail] de Souza et al: J Neuro-Ophthalmol 2024; 44: e455-e456 angiogram, repeat serum studies for AchR blocking and modulating function, thyroid function tests, anti-musclespecific kinase (anti-MuSK), anti-lipoprotein receptor-related protein-4 (anti-LRP4), and ganglioside antibody panel, all of which returned negative. Approximately 8 months after initial presentation to the ED, the patient presented to the neuro-ophthalmology clinic at another institution for further opinion. At that time, his examination was notable for pupillary light-near dissociation (LND), convergence-retraction nystagmus (CRN) in attempted up-gaze saccades, symmetric up-gaze restriction, and asymmetric lid position with left lid 2 mm higher than right. Further work up included repeat MRI of the brain and orbit with 3D constructive interference steady-state (3D-CISS) sequence. During this latest neuro-ophthalmic examination, the patient exhibited persistent manifestations of 3 of the 4 most common features of Parinaud syndrome, a descriptive clinical syndrome describing findings that originate from pathophysiology in the dorsal midbrain.1 The indications observed during this clinical examination would be confirmed by the ordered MRI with 3D-CISS sequence and can be referenced in Figure 1. The 3D-CISS imaging study returned consistent with a remote ischemic infarct in the patient’s dorsal midbrain, potentially from atherosclerotic disease associated with the interpeduncular branches of the basilar artery. Furthermore, the exacerbated adduction deficit and up-gaze palsy experienced by the patient in his right eye were most indicative of a simultaneous right CN III palsy. Thus, the patient’s clinical examination findings and newest imaging results confirmed that his unique set of symptoms was consistent with a partial-Parinaud syndrome accompanied by a partial right CN III palsy, both originating from the small midbrain infarct missed on original imaging without thin cuts through the brainstem. This patient’s acute symptomology was never likely to be associated with MG or an autoimmune source, as originally suspected, because of the patient’s normal NCS results, normal deep tendon reflexes, unremarkable antibody serologies, and incomplete responses to the IVIg, corticosteroid, and mestinon therapies. Furthermore, given the patient’s noted medical history of chronic hypertension, he was at elevated risk for vasculopathy and the level of suspicion for an ischemic stroke should have been high from initial e455 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. T2 coronal (A) and axial (B) MRI sections demonstrating nonenhancing 5-mm hyperintense lesion consistent with chronic infarct. presentation. Previous research has observed that initial MRIs of patients with small cerebral infarcts can produce false-negative rates as high as 53%, demonstrating that routine imaging should not be exclusively used to rule out a potential stroke at the expense of relevant abnormalities on detailed neurologic examination.2 Thus, when the original imaging studies returned unremarkable, considering the clinical presentation, this should have made it clear that the likely infarct occurred in the cerebral microvasculature and indicated progression to more sensitive imaging. 3D CISS MRI sequencing uses constant magnitude transverse and longitudinal magnetic resonance impulses to achieve accentuated T2 relaxation times, making it exceptionally effective for investigating a variety of pathologies related to cranial nerves, vascular anatomy, and cerebrospinal fluid abnormalities.3 3D CISS sequencing also uses extremely thin contiguous sections taken in multiple planes, which makes it useful for detecting minute structures and pathologies that are difficult to evaluate in routine imaging.4 In this case, the original imaging studies were misleading because they lacked adequate sensitivity to detect the small microvascular infarct causing the patient’s symptoms. Because more sensitive imaging was not subsequently ordered based on the clinical localization of the infarct, this resulted in an incomplete differential diagnosis and months of ineffective treatment. This case demonstrates that in cases with high suspicion of focal lesions of the brainstem and negative initial imaging, 3D CISS sequencing can be effective for the localization of small microvasculature strokes likely to be missed by more conventional MRI modalities. After this patient’s confirmed diagnosis, he was started on a daily aspirin regimen to reduce the likelihood of fur- e456 ther infarcts. The patient was also referred to an adult strabismus surgeon to determine whether further strabismus surgery to correct his resulting ocular deviation was clinically appropriate. The patient ultimately underwent successful strabismus surgery to bilaterally recess his lateral rectus muscles and recess his right inferior rectus to correct primary gaze deviations. The patient is diplopia-free at near using reading glasses with ground-in prism approximately 5 months poststrabismus surgery. STATEMENT OF AUTHORSHIP Conception and design: D. de Souza, S. N Grossman; Acquisition of data: D. de Souza, S. N Grossman; Analysis and interpretation of data: D. de Souza, S. N Grossman. Drafting the manuscript: D. de Souza, C. Bell, Z. Elkin, S. N Grossman; Revising the manuscript for intellectual content: D. de Souza, S. N Grossman. Final approval of the completed manuscript: D. de Souza, C. Bell, Z. Elkin, S. N Grossman. REFERENCES 1. Ortiz JF, Eissa-Garces A, Ruxmohan S, et al. Understanding Parinaud’s syndrome. Brain Sci. 2021;6:11. 2. Saber Tehrani AS, Kattah JC, Mantokoudis G, et al. Small strokes causing severe vertigo: frequency of false-negative MRIs and nonlacunar mechanisms. Neurology. 2014;83:169– 173. 3. Cavallaro M, Coglitore A, Tessitore A, et al. Three-dimensional constructive interference in steady state (3D CISS) imaging and clinical applications in brain Pathology. Biomedicines. 2022;10:2997. 4. Hingwala D, Chatterjee S, Kesavadas C, Thomas B, Kapilamoorthy TR. Applications of 3D CISS sequence for problem solving in neuroimaging. Indian J Radiol Imaging. 2011;21:90–97. de Souza et al: J Neuro-Ophthalmol 2024; 44: e455-e456 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.