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.

A Case of Recurrent Painful Ophthalmoplegic Neuropathy Successfully Treated with Beta-blocker Eye Drop Instillation.

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder, which typically occurs in children, and causes headaches and unilateral oculomotor palsy. Early high-dose corticosteroid therapy is recommended to rapidly resolve acute episodes. However, the pathophysiology and therapeutic options for this disorder remain to be fully elucidated. We report a case with typical clinical features of RPON successfully treated with beta-blocker eye drop instillation after the effects of high-dose corticosteroid and other therapies were not sufficient. We propose that beta-blocker eye drop instillation should be considered for patients with corticosteroid-resistant RPON.

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 Painful Ophthalmoplegic Neuropathy with Associated Oculomotor Nerve Tumour.

Recurrent painful ophthalmoplegic neuropathy (RPON) replaced the term 'ophthalmoplegic migraine' as the condition behaves more like an inflammatory cranial neuropathy than a primary headache disorder. RPON may be associated with cranial nerve thickening on MR imaging and persistent oculomotor paresis. Oculomotor tumours have rarely been described in cases of relapsing painful ophthalmoplegia with and without persistent paresis. Here, we present a case of relapsing painful left ophthalmoplegia that gradually became persistent. MR imaging after 14 years of symptoms revealed an enhancing tumour of the left oculomotor nerve. It is unclear whether the tumour was the cause of the attacks or whether repeated cycles could lead to tumour development. MR imaging is indicated in patients with RPON who develop persistent deficits to screen for associated oculomotor tumour.

Facial pain: Overlapping syndromes.

Premise This review summarises the pain syndromes that overlap between headache and facial pain and overlap between pain and cranial nerve lesion. Problem These syndromes share two features in common. First, they show both cranial nerve impairment (e.g. palsy, autonomic dysfunction) and pain; second, they have inflammatory (and/or small vessel) processes as the underlying mechanism. A typical representative of these syndromes is recurrent painful ophthalmoplegic neuropathy, which was previously called ophthalmoplegic migraine and was regarded as a migraine subtype. It is now supposed that this syndrome is caused by an inflammation of one of the ocular motor nerves. Other syndromes discussed in this review are optic neuritis, Tolosa-Hunt syndrome, ischaemic ocular motor nerve palsy, and the very rare Raeder's syndrome. Treatment of all these syndromes is mainly based on steroids. Potential solution Management of possibly underlying disorders such as multiple sclerosis or atherosclerosis should also be considered.

Oculomotor nerve tumors masquerading as recurrent painful ophthalmoplegic neuropathy: report of two cases and review of the literature.

BACKGROUND: In recurrent painful ophthalmoplegic neuropathy (RPON) that was previously termed as ophthalmoplegic migraine, enhancement of the ocular motor cranial nerves could be seen in the cisternal segment during the acute phase. However, various tumors involving the oculomotor nerve may mimic RPON. METHODS: We report two patients with MRI findings of oculomotor nerve schwannoma who initially presented with RPON, and found through the literature review five more patients with oculomotor nerve tumors that masqueraded as RPON. RESULTS: All patients showed an involvement of the oculomotor nerve. The radiological or pathological diagnosis included schwannoma in five, venous angioma in one, and neuromuscular harmatoma in another one. MRIs with gadolinium documented an enhancing nodule involving the cisternal portion of the oculomotor nerve in six of them, which was also observed on follow-up MRIs without an interval change. CONCLUSIONS: It should be recognized that an incomplete recovery may occur during future attacks in patients with otherwise uncomplicated RPON. Follow-up MRIs are required to detect tumors involving the ocular motor cranial nerves, especially in patients with suspected RPON when the recovery is incomplete.

A Case of Adult-Onset Recurrent Painful Ophthalmoplegic Neuropathy With Bilateral Ophthalmoplegia.

Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine, is a disorder typically characterized by recurrent episodes of unilateral headache concurrent with ipsilateral ocular cranial nerve paresis which primarily affects children. Diagnosis is mostly one of exclusion, based on clinical symptoms, supplemented by imaging for enhanced or distorted oculomotor nerves. We present a case of RPON in a 24-year-old adult female with unique features of unilateral left headache with ipsilateral pupillary dilation spreading to bilateral dilation and no MRI findings of oculomotor nerve enhancement.

Recurrent Painful Ophthalmoplegic Neuropathy Responding to Lamotrigine: A Case Report.

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare neurological disorder characterized by recurring ipsilateral headache and paresis of one or more ocular motor nerves. We report the case of a 56-year-old woman with systemic lupus erythematosus (SLE) and hypertension, who presented with severe recurring headaches, nausea, and vomiting. Initially misdiagnosed with cerebral venous sinus thrombosis, her symptoms persisted despite anticoagulant therapy. Further evaluation led to the diagnosis of RPON. Management included intravenous analgesia, hydration, and indomethacin for pain relief. Persistent headache episodes necessitated the introduction of lamotrigine, resulting in significant symptom improvement. However, discontinuation of lamotrigine led to a recurrence of symptoms, which resolved upon resuming the medication. This case contributes to the limited RPON literature, providing insights into its diagnosis and management, with the goal of enhancing awareness and improving patient care.

Tolosa-Hunt syndrome and recurrent painful ophthalmoplegic neuropathy, case reports: what to do and when?

BACKGROUND: Tolosa-Hunt syndrome (THS) and recurrent painful ophthalmoplegic neuropathy (RPON) are rare diseases reported within the "Painful lesions of the cranial nerves" section of the International Classification of Headache Disorders-3rd edition (ICHD-3). In case of a first painful attack, differential diagnosis could be challenging and many pitfalls are due to the rarity of the disorders and the lack of information about correct medical management in youngsters. CASE PRESENTATION: Our main purpose was to report a new case of THS and a new case of RPON describing management and diagnostic investigation at the time of the first episode. In both cases of THS (13 years old) and RPON (14 years old) a unilateral periorbital headache associated with acute onset of ipsilateral third cranial nerve paresis, scarcely responding to non-steroidal anti-inflammatory drugs (NSAID), was present at the beginning of the first attack. Brain MRI with "time-of-flight" (TOF) angiography and the need to administer steroids (after 72 h from onset) in order to stop pain were the most important handles allowing us to adopt the correct management both in THS or RPON since onset and to face recurrences in RPON by avoiding useless therapy during follow-up. CONCLUSION: Unilateral periorbital headache associated with third-fourth or sixth cranial nerve paresis should ideally be investigated with a full work-up, comprehensive of brain MRI with TOF angiography since the first attack. In cases with negative brain MRI spontaneous resolution should be considered and watchful waiting might be advisable before starting steroid therapy.

[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.

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.

Role of Neurovascular Compression of Oculomotor Nerve in Ophthalmoplegic Migraine.

Ophthalmoplegic migraine is considered to occur more commonly in children than in adults. It commonly affects the oculomotor nerve among the cranial nerves. Demyelination of the nerve is proposed as the main mechanism for the etiology of ophthalmoplegic migraine, though it is not fully understood. Neurovascular compression as a cause of ophthalmoplegic migraine has not been well demonstrated in children. In this report, we present a case of a 13-year-old male with recurrent episodes of left ophthalmoplegic migraine. Oculomotor nerve enhancement with swelling was evident on MRI at the exit zone. Magnetic resonance angiography (MRA) revealed a sharp loop of the left posterior cerebral artery compressing the nerve. The case highlighted the unusual etiology of neurovascular compression resulting in ophthalmoplegic migraine in a pediatric patient. A supplemental case of ophthalmoplegic migraine in a seven-year-old male is also shown to highlight the role of neurovascular compression and the importance of using MR angiography to evaluate cases presenting clinically with ophthalmoplegic migraine.

Recurrent Painful Ophthalmoplegic Neuropathy in an Adult Patient: A Case Report With Literature Review.

Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine, is a rare disease that predominantly affects children. Recurrent episodes of ocular cranial nerve paresis with ipsilateral headache characterize this disorder. Diagnosis is mainly clinical with imaging being used as an adjunct. The pathophysiology of the disease is unknown. We present here a case of RPON in a 50-year-old female presenting with multiple episodes of headache and diplopia with associated transient thickening and enhancement of the ipsilateral oculomotor nerve on magnetic resonance imaging (MRI).

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.

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.