Recurrent Painful Ophthalmoplegic Neuropathy Research Articles

Evaluation of Patients with Painful Ophthalmoplegia for Benign and Secondary Etiologies

ABSTRACT This study aims to establish the final definite etiology among patients with long-term follow-up for painful ophthalmoplegia. The data of 44 cases (16 females, 28 females) were examined. In the first diagnosis, subjects were scanned in terms of benign and secondary etiologies. Clinical and radiological follow-up results of patients were recorded. During the follow-up period, data on clinical outcomes (relapse or progression), treatment responses, and final diagnoses were evaluated In total, 49 episodes of painful ophthalmoplegia (44 patients) were evaluated. Secondary etiologies were identified in 21 patients benign/secondary tumours causes in 10, inflammatory in 1, infectious in 3, vascular in 3, demyelinating disease in 1, autoimmune in 2, drug-related cause in 1. 23 patients with benign etiologies; 11 had Tolosa-Hunt syndrome (THS), 2 had Recurrent Painful Ophthalmoplegic Neuropathy (RPON), and 10 had diabetic ophthalmoparesis (DO). 7 of 11 patients with THS met the International Classification Headache Disorders 3rd edition (ICHD-3 beta) criteria, 4 were with a normal MRI, and 1 had a recurrence. 9 of 10 patients with benign/secondary tumours causes were malignant, and 7 died due to disease progression during the treatment process. One of ten patient was followed with diabetic ophthalmoparesis and was diagnosed with cavernous sinus involvement of B-cell lymphoma as a result of clinical progression during follow-up. Painful ophthalmoplegia is a complex clinical condition with a broad differential diagnosis with malignant and benign etiologies. A detailed clinical examination, imaging, and long-term follow-up are essential for accurate diagnosis and treatment management.

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

BackgroundTolosa-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 presentationOur 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.ConclusionUnilateral 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.

Case Report Recurrent Painful Ophthalmoplegic Neuropathy

This is a case report of recurrent painful ophthalmoplegic neuropathy (RPON), a rare disorder characterized by recurrent unilateral headaches and paralysis of the ocular cranial nerves. The condition was previously referred to as ophthalmoplegic migraine but was renamed due to potential misinterpretation of its underlying mechanisms. The case involves a 16-year-old female patient treated at the Hospital do Servidor Público Estadual de São Paulo. She experienced episodes of headache, periorbital pain, and cranial nerve paresis. Neurological examinations and imaging tests ruled out other causes. After diagnosis of RPON was considered, the patient received corticosteroid treatment. This article case report discusses the diagnostic criteria, clinical features, atypical aspects of the case, diagnostic challenges, treatment options, and the unresolved pathophysiology of RPON. Since RPON is a rare syndrome, research relies on observational studies and case reports like the one presented to enhance understanding and treatment approaches.

Erenumab as treatment for recurrent painful ophthalmoplegic neuropathy

Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is a rare condition characterised by recurrent attacks of unilateral headache with ipsilateral ophthalmoplegia. Although classified as a cranial neuralgia, the exact pathophysiology behind RPON is unclear and the clinical presentation often resembles migraine headaches. Here, the authors present the case of a patient with RPON who, after numerous therapeutic failures, received erenumab and experienced significant improvement. This case supports the argument that RPON should be reclassified as a migraine variant, which would enable the use of specific prophylactic medication in patients suffering from this disorder.

A clinical observation of recurrent painful ophthalmoplegic neuropathy in a 49-year old female patient

Recurrent painful ophthalmoplegic neuropathy is a rare clinical syndrome, included into the International Classification of Headache Disorders, 3rd edition, and characterized by recurrent headache episodes associated with dysfunction of one or more ocular motor nerves. The diagnosis implies mandatory exclusion of other potential causes of the symptoms. The paper presents a clinical case of a 49-year old female patient with a unilateral headache paroxysms and subsequent paresis of the oculomotor nerve. A thorough clinical assessment, with neuroimaging (brain magnetic resonance imaging and magnetic resonance angiography of arteries and veins of the head) showed no morphological abnormalities that could cause clinical symptoms of oculomotor neuropathy. Her past history was remarkable for a similar episode of prolonged unilateral headache and oculomotor paresis about 10 years before, which were at that time considered as an acute cerebrovascular accident. Thus, two episodes of similar clinical signs of painful neuropathy, the absence of other possible causes of the disease, and the complete regression of symptoms after treatment (ibuprofen and gabapentin) confirmed the diagnosis of recurrent painful ophthalmoplegic neuropathy.

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

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. 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. 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. Our case gives us the possibility to expand the clinical features of Recurrent Painful Ophthalmoplegic Neuropathy, also contributing to updating the pathophysiological hypotheses.

Could recurrent painful ophthalmoplegic neuropathy be caused by a neurovascular conflict?: A case report

Objective: Describe and discuss a typical case with recurrent painful ophthalmoplegic neuropathy (RPON), and demonstrate a likely extrinsic compression of the sixth cranial nerve by a vascular loop. Background: RPON is a rare, but well-known entity, characterized by attacks of ophthalmoplegia associated with ipsilateral headache. The etiology is unknown, but a neurovascular conflict (NVC) has been suggested as a cause. Method: A 62-year-old woman presented in the emergency department with a horizontal diplopia that developed a few hours after the onset of a left temporal headache. In the past she had presented to the clinic with the same problem several times. She had been thoroughly examined, but no cause had been found. The symptoms had resolved by themselves. In addition to a classic finding in RPON, gadolinium enhancement and thickening of a cranial nerve, the new MRI scanning detected an NVC. Herein we discuss the relevance of this finding. Conclusion: A neurovascular conflict causing inflammatory demyelination of a single cranial nerve and relapsing remitting painful ophthalmoplegic neuropathy is an alluring idea. However, it is hard to conceive theoretically, and more reported cases with compelling data are needed to give credibility to such an idea.

Case report recurrent painful ophthalmoplegic neuropathy

Recurrent Painful Ophthalmoplegic Neuropathy (RPON) is a rare condition, previously known as Ophthalmoplegic Migraine, it is characterized by headache ipsilateral to paresis of the III, IV or VI cranial nerve, usually affects children or young adults. This is a report of a case of RPON in a 16-year-old woman treated at the Hospital do Servidor Público Estadual de São Paulo.

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

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. 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). 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. Elevated serum CGRP levels during the ictal phase of OM/RPON favor migraine as the underlying cause of episodic headache with ophthalmoplegia.

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

ABSTRACT 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

BackgroundOphthalmoplegic 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 presentationThe 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.ConclusionAlthough 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 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).

Adult Onset Recurrent Painful Ophthalmoplegic Neuropathy: Isolated Abducens Paresis

Ophthalmoplegic migraine (OM), previously known as a form of migraine, was defined as recurrent painful ophthalmoplegic neuropathy according to the latest classification of the International Headache Society. The incidence of the disease is 0.7 per million and it is common in childhood. We present a 21-year-old female patient who admitted to our hospital with the complaint of migraine-like headache for 10 days, accompanied by blurred vision and double vision in the right eye within 4 days of its onset. It was learned that she had her first attack of migrainelike headache on the right side, double vision and inability to look outward in the right eye, which lasted about a month, four months ago. In her neurological examination, other examination findings were normal except sixth cranial nerve palsy in the right eye. Adult- onset OM with recurrent isolated sixth nerve involvement was found to be worthy of presentation because of its rarity.

海綿静脈洞近傍の動眼神経にMRI造影効果を認め，頭痛，複視を繰り返した再発性有痛性眼筋麻痺性ニューロパチー類似の14歳男性例

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.

A Clinical Retrospective Study of Recurrent Painful Ophthalmoplegic Neuropathy in Adults.

Introduction Recurrent painful ophthalmoplegic neuropathy (RPON) is quite rare and usually occurs in children. In this report, we describe the clinical features, diagnosis, and treatment of RPON in adults. Methods A retrospective review was conducted of all RPON cases seen and treated at the Zhongshan Ophthalmic Center of Sun Yat-sen University and the Department of Neurology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, over the period from January 2016 to May 2020. Results A total of 8 patients (3 males and 5 females) with a mean age of 42.9 years (range: 23–64 years) met the diagnostic criteria of RPON. Headaches were present prior to the onset of ophthalmoplegic neuropathy in 50% of these patients, while in the remaining 50%, headaches occurred simultaneously with eye symptoms. The degree of these headaches was described as being mild or moderate. Abnormalities involving cranial nerve III were the most frequently reported pathologies (6 cases, 75%), followed by nerve VI (4 cases, 50%) and then nerve IV (1 case, 12.5%) (more than one nerve was affected in some cases). Following either with glucocorticoid treatment or with observation only, symptoms and signs within all 8 patients completely dissipated within 3–28 days. Conclusions All adult cases of RPON along with their clinical features as reported here were similar to those of children.

A case report of isolated abducens nerve palsy: idiopathic or ophthalmoplegic neuropathy?

BackgroundAbducens nerve is the most common nerve affected among other cranial nerves in terms of isolated ocular palsy. Despite its prevalence and progression made in neuroimaging, incidence of idiopathic cases continues to rise.Case presentationWe report a young adult male with no previous illnesses, who presented with sudden onset of binocular diplopia and headache and was later diagnosed with an isolated ipsilateral abducens nerve palsy secondary to an unknown cause and treated with steroids. The palsy and diplopia had resolved in 2-month time but the patient still continued to suffer from a migraine, such as headache.ConclusionAlthough, we labelled the patient as idiopathic initially, another plausible cause for this kind of presentation could be recurrent painful ophthalmoplegic neuropathy (RPON) owing to the nature of the presentation. Cases labelled as idiopathic could be attributed to a defined pathogenesis with detailed history and follow-up. Follow-up is vital for all patients, especially those labelled as idiopathic as recurrence of the illness have the chance of changing the diagnosis if supported by the detailed history and physical examination findings.

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.

Schwannoma Masquerading as Recurrent Painful Ophthalmoplegic Neuropathy: A Diagnostic Dilemma.

Recurrent painful ophthalmoplegic neuropathy, or ophthalmoplegic migraine, is characterized by recurrent cranial nerve paresis following headache. Imaging may demonstrate cranial nerve enhancement during episodes, but absence of structural lesions is required for diagnosis. [J Pediatr Ophthalmol Strabismus. 2020;57:e68-e70.].

Calcitonin gene related peptide in peripheral blood as a diagnostic marker in recurrent painful ophthalmoplegic neuropathy/ophthalmoplegic migraine

Recurrent Painful Ophthalmoplegic Neuropathy (RPON) / Ophthalmoplegic migraine (OM) is a rare neurologic disorder. Its nomenclature, classification and pathophysiology are still debatable despite its initial description dating back to more than a century. While the headache characteristics, temporal profile and response to treatment makes it similar to migraine; the nerve enhancement on imaging points towards a pathology primary to cranial nerves. Our objective was to determine the serum Calcitonin gene related peptide (S.CGRP) levels in peripheral blood in RPON/OM and assess if any correlation exists between the two. 31 clinically suspected RPON/ OM patients were recruited as per the predefined inclusion criteria.16 patients were excluded after investigations.Serum CGRP levels were estimated in ictal and interictal phase (after at least two weeks of clinical resolution of symptoms) and in matched healthy controls. Serum CGRP level were analyzed in 15 patients in ictal phase,12 patients of interictal OM and in 12 age and sex matched healthy controls. S.CGRP levels were found to be significantly elevated (p= 0.048) during the ictal phase (50.2 ng/L) compared to matching controls (33.2 ng/L). Serum CGRP level of 35.46 ng/L ictal phase of ophthalmoplegic migraine patients has sensitivity of 86.7% and specificity of 75%. Serum CGRP levels in the ictal phase, positively correlated with the duration of chronic headaches.There was no gender variability in S. CGRP levels. The raised levels of Serum CGRP levels may indicate a migrainous etiology of this disorder. It may be used as biomarker when in diagnostic dilemma.

Are some ophthalmoplegias migrainous in origin?

The 3rd edition of the International Classification of Headache Disorders replaced the term ophthalmoplegic migraine (OM) with Recurrent Painful Ophthalmoplegic Neuropathy (RPON) based on the presence of contrast enhancement of the involved cranial nerves on Gadolinium-enhanced magnetic resonance imaging. We review our experience and publications concerning ophthalmoplegia, migraine, and RPON. Majority of cases of acute ophthalmoplegia are associated with severe migrainous headaches. A positive history of migraine, increased severity of migraine headaches before the onset of ophthalmoplegia, and the close temporal association between migraine attacks and ophthalmoplegia all suggest an important role played by migraine in the causation of ophthalmoplegia. Enhancement of the involved cranial nerves may be due to the neuro-inflammatory cascade associated with migraine. OM should be considered along with RPON in differential diagnoses of painful ophthalmoplegic syndromes.