Case Presentation: 62 year old woman with Type 2 Diabetes Mellitus and hypothyroidism presented with nausea, vomiting, persistent left sided headache radiating from neck to left eye, left eye pain with left eye and eyelid paralysis for 2 weeks. Patient was well appearing with obvious left eye ptosis and left eye ophthalmoplegia. Examination revealed left cranial nerve 3,4 and 6 palsy. Right eye findings, pupillary reflexes, and the remainder of her neurologic exam were normal. Dilated eye exam was negative for intra-ocular disease and optic nerves appeared healthy. Basic chemistry was unremarkable. MRI brain and orbits were notable for non-specific hyper-intensities of bilateral cerebral white matter and left extra-conal muscles. MRA head and neck to evaluate for vasculitis and serum B12, HIV, and RPR were negative.  Lumbar puncture showed normal cell count, protein and glucose and negative VDRL, HSV, VZV and WNV antibodies. Of note, patient had a prior episode of right sided Bell’s palsy 30 years prior and right sided ophthalmoplegia seven years prior with associated headache that resolved spontaneously. Right temporal artery biopsy at that time was negative. She was started on empiric glucocorticoids and ptosis, ophthalmoplegia and headache improved quickly. A final diagnosis of recurrent painful ophthalmologic neuropathy(RPON) was made.

Discussion: This case provides insight into the work-up and approach to a hospitalized patient presenting with headache and unilateral ophthalmoplegia. It is important to rule out urgent intracranial and intraorbital etiologies such as an intracranial space occupying lesion or lesion affecting the cranial/ optic nerves. These were ruled out with brain imaging and dilated eye exam. We then considered infectious or inflammatory causes like RPON, Miller Fischer syndrome, Tolusa Hunt syndrome, multiple sclerosis, vasculitis, or HSV. Imaging did not meet criteria for multiple sclerosis, and her CSF with HSV PCR was negative. Tolusa Hunt syndrome was a close differential however she had no inflammation of the cavernous sinus on MRI and the disease is almost always unilateral. RPON was deemed the more likely diagnosis given her history of an identical prior episode. RPON formerly called ophthalmologic migraine, is characterized by recurrent painful neuropathy often associated with migraine headache on the ipsilateral side.  The etiology may be related to inflammation, demyelination, or vasospasm in the setting of a migraine. Glucocorticoids are often used as treatment, although this is controversial and not well studied. 

Conclusions: Our case highlights 1) the broad differential and necessity to perform an extensive work up for patient’s with new cranial nerve palsies, focusing on initially ruling out acute orbital or intracranial pathology. 2) The importance of evaluating for infectious causes prior to starting glucocorticoid therapy.