Afferent and Efferent Pupillary Defect With a Right Cranial Nerve Sixth Palsy (the Parkinson Sign) as the Presenting Symptom of Pituitary Apoplexy

The eponymously named ‟Parkinson sign" is a combination of a Horner syndrome and an ipsilateral abducens nerve palsy (cranial nerve VI). The Parkinson sign localizes the lesion to the ipsilateral cavernous sinus.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Afferent and Efferent Pupillary Defect With a Right Cranial Nerve Sixth Palsy (the Parkinson Sign) as the Presenting Symptom of Pituitary Apoplexy Amir Ali, BSA, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Andrew G. Lee, MD T he eponymously named ‟Parkinson sign” is a combination of a Horner syndrome and an ipsilateral abducens nerve palsy (cranial nerve VI). The Parkinson sign localizes the lesion to the ipsilateral cavernous sinus. The Parkinson sign can be a manifestation of a wide range of pathologies, including masses, vascular lesions, inflammation, or trauma in the cavernous sinus. We present a case of a patient with pituitary apoplexy manifesting with the Parkinson sign and an ipsilateral optic neuropathy. To the best of our knowledge, this is the first case of afferent dysfunction present in the Parkinson sign as a manifestation of pituitary apoplexy to be reported in the English language ophthalmic literature. A 64-year-old white man presented with a 5-day history of right eye pain, worse with extraocular movement, binocular horizontal diplopia, nausea, and vomiting. His medical, surgical, and family history were all unremarkable. His medications only included acetaminophen and ibuprofen. The patient had never smoked nor used illicit drugs and had drunk on average 2 standard alcoholic drinks per week. On examination, his visual acuity was 20/50 in the right eye and 20/20 in the left eye. In the dark, pupils were 4 mm in the right eye and 5 mm in the left eye, and there was a right relative afferent pupillary defect (RAPD). Extraocular motility examination revealed an incomitant esotropia (ET) of 25 prism diopters (PD) in primary gaze increasing to 30 PD ET in right gaze consistent with a right abducens nerve palsy. Slit-lamp biomicroscopy and dilated fundus examinations were normal. School of Medicine (AA), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (SR, PWM, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital 6560 Fannin Street, 450 Houston, TX 77030; E-mail: aglee@ houstonmethodist.org e586 FIG. 1. Computed tomography of the brain bony windows showing remodeling of the sella turcica in the axial (A) and coronal (B) planes, highlighted with arrows. MRI of the brain T1 fat-suppressed postgadolinium showing the cystic pituitary lesion in the axial (C) and coronal (D) planes with displacement of the infundibulum, highlighted with arrows. MRI of the brain T1 fat-suppressed in the sagittal plane precontrast (E) showing the blood fluid level and postcontrast (F) showing heterogenous contents of the cystic lesion. Ali et al: J Neuro-Ophthalmol 2022; 42: e586-e587 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Computed tomography (CT) of the brain showed a suprasellar cystic mass with internal hemorrhage consistent with a pituitary macroadenoma and apoplexy. CT angiogram (CTA) of the head and neck was unremarkable. MRI of the brain confirmed a 2.5 · 2.5 · 2.5-cm cystic lesion in and expanding the right pituitary gland, with remodeling of the sella, and pituitary stalk displacement 4 mm left of midline (Fig. 1). There was also superior displacement of the cisternal segment of the right optic nerve and chiasm. Prolactin was elevated at 47 ng/mL (normal 4–15 ng/mL), T4 was decreased as 0.8 ng/dL (normal 0.9–1.7 ng/dL), and random cortisol was ,1 mg/dL (normal range dependent on time of day, but .4 mg/dL). He underwent transsphenoidal resection, and histopathology demonstrated a pituitary adenoma. At his 4-month follow-up appointment, his visual acuity was 20/25 in the right eye and 20/20 in the left eye. His pupils were anisocoric, 4 mm in the right eye and 5 mm in the left eye in the dark and 2.5 mm in the right eye and 3 mm in the left eye in the light. Apraclonidine testing reversed the anisocoria, consistent with a right Horner syndrome. The right RAPD was no longer present. Extraocular motility examination was normal, with resolution of the right cranial nerve (CN) VI palsy. Automated perimetry (Humphrey visual field) was normal, with a mean deviation of 20.49 in the right eye and 20.58 in the left eye. Optical coherence tomography showed an average retinal nerve fiber layer thickness of 88 mm in the right eye and 91 mm in the left eye. Neuro-ophthalmic manifestations of pituitary apoplexy can present with visual acuity deficits (52%), ocular motor nerve palsy, and visual field defects (64%). CN III is the most commonly affected nerve (50%) in patients with cavernous sinus compression (78%) (1). There are varied reports detailing the involvement of CN IV and VI (2,3). Isolated Horner syndrome and light near dissociation are rare manifestations of apoplexy (2). The oculosympathetic fibers travel with the internal carotid artery within the cavernous sinus and travel for a short course on the intracavernous CN VI before heading to CN V. The combination of a Horner syndrome and a Ali et al: J Neuro-Ophthalmol 2022; 42: e586-e587 CN VI palsy is referred to as a Parkinson sign named after the neurosurgeon Dwight Parkinson who first reported it rather than the neurologist James Parkinson, after whom Parkinson disease is named after (4). Clinicians should recognize that a Horner syndrome (miosis, ptosis, and anisocoria greater in the dark) and ipsilateral abducens nerve palsy is the Parkinson sign, which localizes pathology to the posterior cavernous sinus. An ipsilateral RAPD along with the Parkinson sign maybe an indication of more extensive pathology involving the cavernous sinus and part of the optic pathway. In the acute setting, this should raise suspicion for pituitary apoplexy. To the best of our knowledge, this is the first such case to be reported in the English language ophthalmic literature. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; b. Acquisition of data: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; c. Analysis and interpretation of data: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. Category 2: a. Drafting the manuscript: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; b. Revising it for intellectual content: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: A. Ali, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. REFERENCES 1. Murad-Kejbou S, Eggenberger E. Pituitary apoplexy: evaluation, management, and prognosis. Curr Opin Ophthalmol. 2009;20:456–461. 2. Simon S, Torpy D, Brophy B, Blumbergs P, Selva D, Crompton JL. Neuro-ophthalmic manifestations and outcomes of pituitary apoplexy—a life and sight-threatening emergency. N Z Med J. 2011;124:52–59. 3. Saffra N, Kaplow E, Mikolaenko I, Kim A, Rubin B, Jafar J. Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report. BMC Ophthalmol. 2011;11:4. 4. Parkinson D, Johnston J, Chaudhuri A. Sympathetic connections to the fifth and sixth cranial nerves. Anat Rec. 1978;191:221– 226. e587 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.