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.

Serum Calcitonin Gene-Related Peptide Is Elevated in Patients With Migraine and Ophthalmoplegia.

BACKGROUND: There is ongoing debate about whether the oculomotor (III), trochlear (IV), or abducens (VI) nerve paresis in patients with migraine is directly attributable to migraine (ophthalmoplegic migraine [OM]) or is due to an inflammatory neuropathy (recurrent painful ophthalmoplegic neuropathy [RPON]). As migraine is associated with elevated serum calcitonin gene-related peptide (CGRP) levels, we studied serum CGRP levels among patients with OM/RPON to determine whether they are elevated during and between attacks. This is the first study assessing CGRP levels in the serum of patients with OM/RPON. METHODS: The aim of this case-control study was to assess serum CGRP levels in patients with ophthalmoplegia and a headache consistent with migraine according to ICHD-3 criteria. Serum CGRP levels were measured during the ictal and interictal phases in 15 patients with OM/RPON and compared with age-matched and sex-matched controls without migraine (12 patients). RESULTS: The median serum CGRP levels were significantly elevated ( P = 0.021) during the ictal phase (37.2 [36.4, 43.6] ng/L) compared with controls (32.5 [30.1, 37.3] ng/L). Serum CGRP levels during the attack correlated with the total duration of ophthalmoplegia. A CGRP level of 35.5 ng/L in the ictal phase of the attack had a sensitivity of 86.7% and specificity of 75.0% in diagnosing a patient with OM/RPON. CONCLUSIONS: Elevated serum CGRP levels during the ictal phase of OM/RPON favor migraine as the underlying cause of episodic headache with ophthalmoplegia.

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.

From ophthalmoplegic migraine to cranial neuropathy.

Ophthalmoplegic migraine (OM)/recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disease consisting of recurrent unilateral headache accompanied or followed by ipsilateral ophthalmoplegia. Because MRI findings suggest neuropathy and the relationship to typical migraine remains unclear, the disease has been renamed from "ophthalmoplegic migraine" to "recurrent painful oculomotor neuropathy" in the third edition of the International Classification of Headache Disorders (ICHD). However, it remains a fact that most cases of OM/RPON described in the literature have a history of migraine and that the headache during OM/RPON often has migrainous features. A more detailed clinical description of the headache during OM/RPON and additional results from imaging and possibly histology will be needed to better understand the pathophysiology of the disease and its relationship to typical migraine.

Vertical components of head-shaking nystagmus in vestibular neuritis, Meniere's disease and migrainous vertigo.

OBJECTIVES: To describe vertical and horizontal components of head-shaking nystagmus (HSN) in various vestibular disorders. DESIGN: Retrospective case review. SETTING: Tertiary care academic referral centre. PARTICIPANTS: Head-shaking nystagmus was assessed in 66 vestibular neuritis (VN) patients at acute (<7 days) and follow-up (2 months), and 65 Meniere's disease (MD) and 76 migrainous vertigo (MV) in interictal period. MAIN OUTCOME MEASURES: Head-shaking nystagmus was categorised as pure horizontal, pure vertical or mixed. Horizontal HSN was classified as monophasic or biphasic and paretic or recovery. Vertical HSN was classified as upbeat or downbeat. RESULTS: Abnormal HSN (pathologic monophasic, biphasic or delayed-peak HSN) showed different positive rates depending on the vestibular disorders and compensation (94% in acute VN; 89% in FU VN; 78% in MD; 50% in MV). Paretic HSN with the nystagmus towards the lesioned side was the most common type in VN and MD; however, recovery HSN with the nystagmus towards the intact side could be rarely observed especially in patients with MD or compensated VN. Vertical nystagmus could be combined with horizontal HSN, and upbeat HSN was observed in most (83%) of the patients with acute VN, but downbeat HSN was common in follow-up VN (83%), MD (97%) and MV (85%). Weak perverted HSN, which is assumed to be a central nystagmus, was rarely observed in MD and MV (6-9%), but not in VN. CONCLUSIONS: Head-shaking nystagmus (HSN) in horizontal plane is a valuable tool in the assessment of vestibular imbalance. Common observation of upbeat HSN in acute VN and downbeat HSN in follow-up VN, MD and MV suggests that vertical components are possibly related to the involvement of vestibular apparatus and compensation. Weak perverted HSN and delayed-peak HSN were rarely observed in MD and MV, and never observed in VN, suggesting that it is possibly related to either asymmetrically impaired vertical canals or misorientation of the velocity-storage system.

Ophthalmoplegic migraine: migraine or oculomotor neuropathy?

BACKGROUND: Ophthalmoplegic migraine (OM) is a rare condition characterized by the association of headaches and an oculomotor nerve palsy. The third cranial nerve is commonly involved in recurrent attacks, whereas involvement of the sixth and fourth nerves is uncommon. It is still debated whether an uncontrolled migraine or an oculomotor neuropathy may be the primary cause of ophthalmoplegic migraine. CASES: We report two patients affected by OM with normal magnetic resonance imaging findings and a history of uncontrolled migraine before an attack of OM. CONCLUSION: The cases reported allow us to hypothesize that OM may be considered a form of migraine rather than a cranial neuralgia. It is possible that different factors such as inflammatory or structural factors, may represent a vulnerability of the nerve during a severe migraine attack causing ophthalmoplegia.

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.

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 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: Migraine, Neuralgia, or Something Else?

Recurrent painful ophthalmoplegic neuropathy (RPON) is a very rare disease characterized by recurrent attacks (at least two) of unilateral headache associated with ipsilateral ophthalmoplegia due to paresis of one or more cranial motor nerves, not due to any orbital, parasellar, or posterior fossa lesions. The differential diagnoses for this condition are broad. In addition to disability during an acute attack, this disease could also cause a permanent neurologic deficit. The understanding of RPON pathogenesis has changed over time, leading to a change in the classification of this disorder between editions of the International Classification of Headache Disorders, in which the condition was moved from the chapter on migraine to the chapter on cranial neuralgias and central causes of facial pain. There is no consensus on the pathogenesis of RPON. It is possible that multiple pathogenic mechanisms underlie various clinical forms of the disease. A depiction of pathologic analyses of patients with radiologically confirmed changes in the affected nerves during and outside of attacks would significantly contribute to knowledge of its pathogenesis. Brain imaging should be performed in each patient during an acute RPON attack and at a regular schedule between attacks. Further case reports and case series are required before further conclusions can be made regarding RPON pathogenesis and proposals for treatment options.