An 8-year-old boy presented to the emergency room with complaints of right-sided ptosis, accompanied by a severe headache and vomiting that had progressively worsened over the previous week. Since the age of three, the patient had experienced headaches three to four times annually, each episode typically accompanied by vomiting. Most of these headache attacks were alleviated with analgesics such as acetaminophen or ibuprofen. However, 4 years prior to this visit, the patient began experiencing more severe headaches and vomiting that were unresponsive to analgesics. Consequently, he was admitted to a local hospital for imaging and pain management. At that time, he exhibited mild exotropia in the right eye but was discharged a few days later following headache relief and normal magnetic resonance imaging (MRI) results. The mild exotropia in the right eye improved within 1 week of discharge.

The neurological examination revealed no abnormalities in the cranial nerves other than right eyelid ptosis. An ophthalmic examination, including an ice test to rule out myasthenia gravis, yielded normal results. Complete blood tests, serologic tests, and C-reactive protein levels were also within normal limits. While awaiting further evaluation, the patient reported diplopia and a mild restriction in the upward and medial gaze of the right eye. He was admitted for a cerebral spinal fluid (CSF) analysis and brain imaging to investigate potential central nervous system issues. The CSF analysis indicated no pleocytosis and normal protein levels, but showed an increased intracranial pressure (IICP) of 30 cmH₂O. Treatment with mannitol infusion was initiated to manage the IICP. MRI of the brain revealed a 5 mm nodular enhancing lesion at the right crural cistern, raising the possibility of a neurogenic tumor (Fig. 1A). Given his medical history, we reviewed the previous MRI from another hospital taken 4 years earlier. This review confirmed the presence of a nodular, enhancing lesion in the same location (Fig. 1B). Thus, we diagnosed him with ophthalmoplegic migraine and commenced treatment with prednisolone at a dosage of 2 mg/kg/day. In the first 2 days of treatment, his symptoms worsened, showing increased right ptosis, mydriasis, and limited upward and downward gaze, as well as adduction of the right eye. However, his symptoms gradually improved thereafter, and he was discharged on the 8th day with prednisolone. At the outpatient clinic, he continued to recover and was gradually tapered off prednisolone 1 month later. Repeated MRI scans conducted 3 and 8 months post-discharge showed significant reductions in both the intensity and size of the focal enhanced nodular lesion (Fig. 1C and D).

RPON is a rare disorder characterized by paralysis of the third, fourth, or sixth cranial nerves following a headache. The headache may occur up to 14 days before ipsilateral paresis of the ocular motor nerves. Repeated episodes can suggest the diagnosis, which is confirmed by MRI evidence of nerve thickening during an episode [1]. The prevalence of RPON is estimated at approximately 0.7 cases per million [2]. Although most cases begin in childhood, with an average age of onset at 8 years, the early onset of the first attack in infancy or childhood makes RPON challenging to diagnose in this population [3].

RPON is diagnosed by ruling out other disorders, and a diagnosis can only be confirmed when at least two attacks meet the specified criteria. Brain imaging plays a crucial role in excluding structural lesions in the orbital, parasellar, or posterior fossa regions. However, brain imaging alone is insufficient to determine whether the condition is related to metabolic issues, neoplasms, systemic inflammation, or infections. Differentiating neoplastic diseases such as schwannoma, which can be easily mistaken for RPON, is challenging. This is because tissue biopsy, which is highly invasive and often not feasible due to the risk of permanent disability, is the primary method for differentiation [4]. Consequently, lesions that enhance and show progressive growth over time on follow-up imaging may provide better indications of neoplastic diseases [5]. Nevertheless, the clinical practice does not always allow sufficient time to wait for verification of follow-up images, making the patient’s medical history crucial for diagnosing RPON. In this instance, the patient was diagnosed with RPON after a thorough review of his medical history and previous MRI scans.

The thickening and enhancement of one or more of the ocular cranial nerves, most commonly the oculomotor nerve, observed in brain imaging, coupled with a history of a previous attack, can aid in diagnosing RPON [6,7]. In most cases of RPON, if symptoms improve, follow-up brain MRI typically shows a reduction or complete resolution of focal enhancement in the cisternal portion of the involved nerve, a finding that is uncommon in schwannoma. In the case of our patient, MRI confirmed a reduction in size following treatment, supporting the diagnosis of RPON.

In most cases of RPON, ophthalmoplegia resulting from cranial nerve palsy tends to improve following the resolution of headache attacks. However, with repeated recurrences, permanent neurological sequelae such as ptosis or exotropia can persist in up to 30% of patients [8]. In such instances, surgical intervention may be necessary. Indeed, in our case, the exotropia did not resolve even after 21 months, leading to the patient undergoing a right rectus muscle resection operation.

In conclusion, we have reported a case of RPON characterized by ptosis and exotropia, followed by a severe headache attack. The diagnosis was challenging due to the similarity of the imaging findings to those of a schwannoma. Treatment options may vary based on the accurate diagnosis. Therefore, it is crucial for clinicians to thoroughly review the patient's medical history when diagnosing RPON.

This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2203-742-702). The review board waived the need for informed consent owing to the study's retrospective nature.