Recurrent Painful Ophthalmoplegic Neuropathy: A case report with atypical features and a review of the literature.

INTRODUCTION: Recurrent Painful Ophthalmoplegic Neuropathy, previously known as Ophthalmoplegic Migraine, is a poorly characterized disorder mainly because there are few cases described. We report a new case of Recurrent Painful Ophthalmoplegic Neuropathy and a review of the literature to contribute to increasing the knowledge of the clinical features of this disorder. CASE REPORT AND REVIEW OF LITERATURE: A 45-year-old woman presented with adult-onset recurrent attacks of abducens and oculomotor palsy associated with diplopia followed by headache. Most notably, pain always presented many days after oculomotor impairment, a feature never described in the literature. A diagnosis of possible Recurrent Painful Ophthalmoplegic Neuropathy was made after excluding other possible mimicking disorders. Symptoms usually resolved gradually with corticosteroid therapy, albeit without a clear-cut benefit.Clinical data collected from 1989 to 2022 showed that adult onset in Recurrent Painful Ophthalmoplegic Neuropathy is not uncommon. While III cranial nerve palsy is typical, VI and IV nerve palsy have also been described. PATHOPHYSIOLOGY AND DIAGNOSIS: Several hypotheses have been proposed, including nerve compression, ischemia or inflammation/demyelination, but none has been completely accepted.Diagnosis remains of exclusion; magnetic resonance imaging and blood exams are key in differential diagnosis. CONCLUSIONS: Our case gives us the possibility to expand the clinical features of Recurrent Painful Ophthalmoplegic Neuropathy, also contributing to updating the pathophysiological hypotheses.

Proposed modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy: Five case reports and literature review.

BACKGROUND: Recurrent painful ophthalmoplegic neuropathy (RPON) is an uncommon disorder characterized by recurrent unilateral headache attacks associated with ipsilateral ophthalmoplegia. We intend to study the clinical picture in our case series along with the published literature to discuss the pathogenesis and propose modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy. METHODS: We reported five cases diagnosed as ophthalmoplegic migraine/RPON in our medical centers and reviewed the published literature related to RPON from the Pubmed database between 2000 and 2020. In one of these cases, a multiplanar reformation was performed to look at the aberrant cranial nerve. RESULTS: The mean onset age for RPON was 22.1 years, and the oculomotor nerve was the most commonly involved cranial nerve (53.9%) in 165 reviewed patients. In most patients, ophthalmoplegia started within 1 week of the headache attack (95.7%, 67/70). Additionally, 27.6% (40/145) of patients presented enhancement of the involved nerve(s) from MRI tests. Finally, 78 patients received corticosteroids, out of which 96.2% benefited from them. CONCLUSION: This is the first time multiplanar reformation has been performed to reveal the distortion of the oculomotor nerve. Modified diagnostic criteria are proposed. We hope to expand the current knowledge and increase the detection of recurrent painful ophthalmoplegic neuropathy in the future.

[A case of recurrent headache and ophthalmoplegia with a contrast-enhanced lesion of the oculomotor nerve in the cavernous region: an atypical phenotype of recurrent painful ophthalmoplegic neuropathy].

The patient was a 14-year-old boy with two previous episodes of self-remitting right ophthalmoplegia with right temporal pain at ages 9 and 12. In 2019, he developed right eyelid ptosis and diplopia 2 days after a pulsating right-sided temporoparietal headache. Recurrent headaches with ophthalmoplegia responded to high-dose steroid therapy, and the clinical features resembled recurrent painful ophthalmoplegic neuropathy (RPON). RPON generally presents with MRI findings of hypertrophy and inflammation at the root of the oculomotor nerve, a vulnerable site of the blood-brain barrier. However, the imaging features in this case were different from those in typical cases of RPON, and oculomotor nerve inflammation was found in the cavernous sinus. The order of onset of headache and oculomotor nerve palsy differed in each recurrence, suggesting that both autoimmune and vascular mechanisms may have been involved in the onset of the disease in our case.

Recurrent Painful Ophthalmoplegic Neuropathy with Unilateral Oculomotor and Trochlear Nerve Palsy in an 8-year-old Girl.

BACKGROUND: Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder with a unilateral headache accompanied by ipsilateral episodes of painful ocular cranial nerve neuropathy, which typically occurs in childhood. CASE REPORT: We report an 8-year-old female with four episodes of RPON involving unilateral third and fourth cranial nerves. Right eye exotropia and complete ptosis were detected on examination. Brain MRI images revealed right third nerve enhancement where it exits from the brainstem. She completely recovered after 5 weeks with the administration of prednisolone and indomethacin. DISCUSSION AND CONCLUSION: Due to the rarity of this condition in children, recurrent painful ophthalmoplegic neuropathy should be considered as a differential diagnosis of unilateral or bilateral painful ophthalmoplegia, particularly with a history of migrainous headache. Since it is a treatable entity, and repeated attacks may lead to permanent sequela, early intervention is crucial.

Diagnostic controversies in recurrent painful ophthalmoplegic neuropathy: single case report with a systematic review.

BACKGROUND: Ophthalmoplegic migraine, renamed "Recurrent Painful Ophthalmoplegic Neuropathy" (RPON) in 2013 by the International Headache Society is a rare neurologic disorder characterized by recurrent attacks of ophthalmoplegia associated to ipsilateral headache. The etiology is still unknown. Typical magnetic resonance imaging findings show a focal nerve thickening and contrast enhancement. In the majority of cases, there is a full recovery within days or weeks. There is no evidence supporting a specific treatment. The review defines the characteristics of the recurrent painful ophthalmoplegic neuropathy in patients within 2 years of age underlying the importance of the role of magnetic resonance imaging even in presence of the first attack. Thus, an emblematic case report is presented. CASE PRESENTATION: The authors present a case of third cranial nerve paresis in a 17-month-old male child, presenting a neuroradiological pattern highly suggestive of schwannoma, aneurism or recurrent painful ophthalmoplegic neuropathy. Thus, a review of the literature with the pediatric casuistry of recurrent painful ophthalmoplegic neuropathy occurred within 2 years of age focusing on diagnostic considerations is presented. The authors highlight the importance to consider recurrent painful ophthalmoplegic neuropathy in presence of magnetic resonance imaging findings and clinical symptoms referable to aneurysm or schwannoma. Thus, the review defines the characteristics and the neuroradiological findings at the first RPON attack occurred under 2 years of age. CONCLUSION: Although two attacks are necessary, the review strongly suggests to consider recurrent painful ophthalmoplegic neuropathy even at the first attack, in presence of described characteristics and the aforementioned magnetic resonance imaging findings.

A case of adult-onset ophthalmoplegic migraine.

Ophthalmoplegic migraine (OM) also called recurrent painful ophthalmoplegic neuropathy (RPON) is not a so common disorder. It is characterized by childhood onset, ophthalmoplegia and migraine type of headache. The most common involved nerve is third cranial nerve. Involvement of fourth and sixth cranial nerve is unlikely. Adult cases are not so common. This is a case report of a man who presented with left-sided severe headache and diplopia of left eye. He had left oculomotor nerve palsy. The patient responded to treatment and recovered.

Recurrent painful ophthalmoplegic neuropathy revealing oculomotor nerve schwannoma.

Painful ophthalmoplegia is a common presenting symptom in neuro-ophthalmology emergencies. We report an unusual case of a recurrent painful ophthalmoplegia due to a third nerve schwannoma mimicking « ophthalmoplegic migraine ¼. A 18 year-old girl had presented 4 episodes of left eye painful ophthalmoplegia respectively in 8, 13, 16 and 17 years old. One year after the last episode, neurological examination was normal. Brain MRI focused on the oculomotor nerve showed an enhancing nodular lesion suggesting a third nerve schwannoma. Thus, recurrent painful ophthalmoplegia revealing oculomotor nerve schwannoma, as described in our case, is exceptional. To our knowledge, only thirteen cases have been reported in the literature. Third nerve schwannoma is a rare cranial nerve tumor, typically revealed by progressive palsy of the oculomotor nerve. Recurrent painful ophthalmoplegia with persistent headache and enhancement in brain imaging should suggest tumoral lesions.

Recurrent painful ophthalmoplegic neuropathy: a cause for recurrent third nerve palsy in a child.

Recurrent painful ophthalmoplegic neuropathy (RPON), previously called ophthalmoplegic migraine, is a rare condition characterised by recurrent episodes of headache and ophthalmoplegia. We report a case of 11-year-old girl with recurrent painful ophthalmoplegia due to isolated right oculomotor nerve involvement. MR brain imaging showed enhancing lesion of cisternal segment of right oculomotor nerve. A possibility of Tolosa Hunt syndrome was considered and she was treated with glucocorticoids, followed by azathioprine due to recurrence. In the fourth episode, she developed migraine headache followed by right third nerve palsy, after which the diagnosis was revised to RPON. She was started on flunarizine along with short-term glucocorticoids. At 1-year follow-up, she remained asymptomatic. RPON should be considered in patients with recurrent third nerve palsy to avoid inadvertent long-term exposure to immunosuppressive agents.

Recurrent Painful Ophthalmoplegic Neuropathy with Residual Mydriasis in an Adult: Should it Be Classified as Ophthalmoplegic Migraine?

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare condition that manifests as headache and ophthalmoplegia. It typically occurs in children. Although migraine or neuropathy have been suggested as etiologies, the precise etiology remains unclear. In the International Classification of Headache Disorders 3rd edition-beta version (ICHD3ß) (code 13.9), RPON was categorized into painful cranial neuropathies and other facial pains. We encountered a 48-year-old woman who had diplopia and right ptosis. The administration of prednisolone led to the immediate improvement of her oculomotor palsy, but residual mydriasis remained. Based on this case, the pathophysiology of RPON may involve temporary nerve inflammation with migraine. Repeated and severe migraine attacks may cause irreversible nerve damage. Thus, medication for migraine prophylaxis might be needed to prevent RPON.

Ophthalmoplegic migraine with persistent dilated pupil.

Ophthalmoplegic migraine is a rare disorder characterized by childhood-onset ophthalmoplegia and migraine headaches. The third cranial nerve is commonly involved, while involvement of the sixth and fourth cranial nerves is uncommon. We present the case study of a 15-year-old female teenager whose condition was diagnosed with ophthalmoplegic migraine when she was 9 years old and since then has experienced multiple and recurrent attacks. Since the diagnosis, she has exhibited a persistent right-eye mydriasis, despite resolution of migrainous episodes. Pupillary involvement in ophthalmoplegic migraine is the rule in children, with total recovery in the majority of cases. We will discuss some aspects related to the eventual association between this entity and other comorbidities, such as Adie tonic pupil, emphasizing the fact that the underlying mechanisms of this residual mydriasis are not fully understood.

[A 56-year-old woman with adult-onset ophthalmoplegic migraine presenting with recurrent bilateral abducens nerve palsy].

A 56-year-old woman had been experiencing episodic left eye pain followed within 3 days by double vision and adduction of the left eye since the age of 30. The episodes occurred once per month, and her symptoms spontaneously resolved within 3 days. The patient was diagnosed with ophthalmoplegic migraine (OM) with left abducens nerve palsy at the age of 53 years. In May 2011, she developed bilateral retro-orbital pain followed by double vision and limitation of abduction of the right eye. She recalled having a cold and high fever 10 days before the onset of the headache. MRI showed no thickening or enhancement of the right abducens nerve. Constructive interference in steady-state (CISS) MRI showed neurovascular contact between the right abducens nerve and anterior inferior cerebellar artery. Right abducens nerve palsy accompanied by OM was diagnosed after other diseases that can cause ophthalmoplegia were excluded. The patient's eye symptoms gradually improved following steroid treatment. There have been a few similar case reports of adult patients with OM showing left and right abducens nerve palsy at different time points. In this case report, we discuss the possible mechanisms related to OM.

Ophthalmoplegic "migraine" or recurrent ophthalmoplegic cranial neuropathy: new cases and a systematic review.

Ophthalmoplegic migraine is a poorly understood neurologic syndrome characterized by recurrent bouts of head pain and ophthalmoplegia. By reviewing cases presenting to our centers in whom the phenotype has been carefully dissected, and systematically reviewing all published cases of ophthalmoplegic migraine in the magnetic resonance imaging (MRI) era, this review sets out to clearly define the syndrome and discuss possible etiologies. We found that in up to one-third of patients, the headache was not migrainous or associated with migrainous symptoms. In three-quarters of the cases involving the third nerve, there was focal nerve thickening and contrast enhancement on MRI. Observational data suggest systemic corticosteroids may be beneficial acutely. The etiology remains unclear, but may involve recurrent bouts of demyelination of the oculomotor nerve. "Ophthalmoplegic migraine" is a misnomer in that it is probably not a variant of migraine but rather a recurrent cranial neuralgia. A more appropriate name might be "ophthalmoplegic cranial neuropathy."

Adult-onset migraine-related ophthalmoplegia and omolateral fetal-type posterior cerebral artery.

A 33-year-old woman with a long history of typical migraine without aura developed a pupillary-involving right third nerve palsy, after a typical migraine attack. The right pupil was 5 mm and showed delayed direct and consensual photomotor responses; the left pupil was 3 mm and reactive. Pupillary reaction to convergence was slow on the right eye. Ptosis, impaired elevation of the eye and weakened adduction were noted in the right eye. CT scan of the brain showed no abnormalities, whereas a CT digital cerebral angiography revealed a fetal-type right posterior cerebral artery (PCA). MRI disclosed thickening and contrast-enhancement of the cisternal portion of the right oculomotor nerve. A lumbar puncture, performed 5 days after the onset of ocular symptoms, yielded acellular cerebrospinal fluid (CSF) with normal protein and glucose levels. Ptosis and diplopia recovered within a week, whereas blurred vision, anisocoria and accommodation deficit subsided after 10 weeks.