Highlights
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• Atypical recurrent painful ophthalmoplegia neuropathy (RPON) cases broaden the spectrum and challenge its disease definition.
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• Facial neuropathy is common in RPON, uniformly peripheral, and may recur.
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• RPON may involve non-ocular cranial nerves, consistent with inflammatory neuropathy.
Introduction
Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is a rare disorder characterized by recurrent episodes of paresis affecting one or more ocular motor cranial nerves accompanied by ipsilateral headache, and it remains a diagnosis of exclusion. 1,Reference Kim, Kang, Kang and Lee2 In the first edition of the International Classification of Headache Disorders (ICHD), OM was classified as a subtype of migraine, although migrainous headache was not included in its diagnostic criteria. 3,Reference Furia, Liguori and Donadio4 With the increasing use of brain MRI, reversible thickening and contrast enhancement of the affected cranial nerve were reported in patients with OM. Reference Furia, Liguori and Donadio4,Reference Mark, Blake, Atlas, Ross, Brown and Kolsky5 These observations supported a potential inflammatory mechanism underlying OM. Reference Furia, Liguori and Donadio4 Reflecting this shift, OM was reclassified under cranial neuralgias and central causes of facial pain in the second edition of the ICHD, and the diagnostic criteria were revised to require migrainous headache. Reference Furia, Liguori and Donadio4 In the third edition of the ICHD published in 2018, the term OM was replaced with RPON, and the requirement for migrainous headache was removed from the diagnostic criteria. 1 Nevertheless, many patients with RPON continue to report migrainous headache or migraine-associated symptoms, suggesting that a link to migraine pathophysiology may persist despite this change. Reference Furia, Liguori and Donadio4
RPON typically presents in childhood or adolescence, occurs more often in females and is commonly associated with migrainous headache, with the oculomotor nerve being the most frequently affected. Reference Furia, Liguori and Donadio4,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Liu, Wang and Bian7 However, an increasing number of atypical cases have expanded the recognized spectrum of RPON and raised questions regarding its disease definition. Reference Kim, Kang, Kang and Lee2,Reference Furia, Liguori and Donadio4,Reference Liu, Wang and Bian7,Reference Dhoot and Sengupta8 Involvement of cranial nerves not responsible for ocular movement, including the trigeminal, facial and hypoglossal nerves, has rarely been reported within the presumed RPON spectrum. Reference Kim, Kang, Kang and Lee2,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Hutchinson and Donaldson9 This study aims to determine the frequency of involvement of these additional cranial nerves in patients who met the diagnostic criteria for RPON and to evaluate the clinical significance of such findings.
Methods
Study enrollment and ethical approval
Patients were consecutively enrolled from those who visited Chonnam National University Hospital between January 2008 and April 2025. This study was conducted in accordance with the recommendations of the Institutional Review Board of Chonnam National University Hospital (IRB number: CNUH-2025-282). All study subjects provided written informed consent in accordance with the Declaration of Helsinki.
Inclusion and exclusion criteria
Based on the diagnostic criteria of the third edition of the ICHD, inclusion required at least two attacks of paresis involving one or more ocular motor cranial nerves with ipsilateral headache. In addition, all patients underwent repeated evaluations to exclude other possible causes of painful ophthalmoplegia, including Tolosa–Hunt syndrome (THS), anti-GQ1b syndrome and orbital or parasellar lesions.
Diagnostic workup
To exclude alternative diagnoses, patients underwent a comprehensive laboratory and imaging workup. CSF cytology and gadolinium-enhanced brain MRI were performed, and a panel of anti-ganglioside antibodies was tested, including anti-GD1b IgM, anti-GD1b IgG, anti-GM1 IgM, anti-GM1 IgG, anti-GQ1b IgM and anti-GQ1b IgG. Additional testing included acetylcholine receptor antibodies and a full autoimmune marker panel, consisting of antinuclear antibody, anti-double-stranded DNA antibody, anti-neutrophil cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-SSA/Ro antibody, anti-SSB/La antibody and complement levels (C3 and C4). Tumor markers assessed included alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19–9. Carbohydrate antigen 15–3 was measured in female patients, and prostate-specific antigen was measured in male patients.
MRI protocol
Brain MRI followed the standard imaging protocol of Chonnam National University Hospital when patients presented with an ophthalmoplegic attack or facial neuropathy. The protocol consisted of diffusion-weighted imaging, fluid-attenuated inversion recovery, gradient-echo imaging, time-of-flight magnetic resonance angiography and sequential gadolinium-enhanced imaging.
Neurological and neuro-ophthalmological evaluation
Comprehensive neurological and neuro-ophthalmological evaluations were performed for each attack by experienced neuro-ophthalmologists (JMK, SHL). Bedside examinations were used to assess the function of each cranial nerve, and when dysfunction was suspected, additional objective testing was performed. These tests included nine-cardinal gaze photography and fundus photography for the ocular motor nerves (cranial nerves III, IV and VI), as well as facial nerve conduction studies and blink reflex testing for the facial nerve.
Pain, headache and clinical data collection
To characterize pain or headache preceding ophthalmoplegia, we recorded onset pattern, duration, quality, location, severity and associated symptoms, particularly migrainous features. Baseline characteristics, clinical information and neuro-radiological findings were collected for all enrolled patients. To assess vascular risk factors, we reviewed medical histories for hypertension, diabetes mellitus, hyperlipidemia, cardiovascular disease and cerebrovascular disease. Laboratory evaluations included lipid profiles and hemoglobin A1c.
Results
Representative case 1 (Patient 3)
A previously healthy 48-year-old man presented with binocular horizontal diplopia for three days. He denied any history of diplopia, migraine or head trauma but reported a prior self-limiting episode of diplopia that had resolved within a month about 10 years earlier. Ten days before the onset of ophthalmoplegia, he experienced a moderate-to-severe throbbing headache localized to the ipsilateral periorbital and frontal regions, without migraine aura or other migraine-associated symptoms. Neurological examination showed an abduction deficit in the right eye, consistent with isolated right abducens nerve palsy (Supplementary Figure 1), while the rest of the neurological and cranial nerve examinations were unremarkable. Brain MRI with gadolinium enhancement revealed no abnormalities. To further evaluate the differential diagnosis, CSF cytology and serologic tests for anti-ganglioside antibodies, acetylcholine receptor antibodies and autoimmune and tumor markers were performed, all yielding negative results. Empirical high-dose intravenous corticosteroids (1 g/day for five days) were administered, resulting in complete pain relief within two days and gradual resolution of diplopia over the following month.
Seven months later, the patient returned with facial asymmetry and a three-day history of stabbing pain in the left postauricular region. He reported no recent infection or upper respiratory symptoms. Neurological examination revealed impaired eye closure, drooping of the mouth and reduced facial expression on the left side, findings suggestive of left-sided lower motor neuron facial nerve palsy. No other cranial nerve deficits, motor or sensory abnormalities or cerebellar signs were noted. Gadolinium-enhanced brain MRI showed focal enhancement in the labyrinthine segment of the left facial nerve (Figure 1A). The patient was treated empirically with oral steroids and acyclovir, resulting in complete symptom resolution within approximately 20 days.
Focal enhancement of the facial nerve on brain MRI in representative patients. During episodes of facial neuropathy, several patients (A: Patient 3; B: Patient 1) show asymmetric enhancement in the labyrinthine segment of the facial nerve on gadolinium-enhanced brain MRI (white and dotted arrows).
Figure 1. Long description
The MRI scan of the brain highlights asymmetric enhancement in the labyrinthine segment of the facial nerve for two patients. In image A, labeled as Patient 3, a dotted arrow points to the area of enhancement. In image B, labeled as Patient 1, a solid white arrow indicates the same. These enhancements are visible during episodes of facial neuropathy and are captured using gadolinium-enhanced brain MRI.
Diplopia recurred twice in the following years, at intervals of approximately 1.5 years (Figure 2). In the first instance, he developed left abducens nerve palsy preceded by an ipsilateral headache lasting 10 days; intravenous corticosteroids were administered, leading to complete recovery within two weeks. In the second instance, he presented with right abducens nerve palsy without preceding headache and treatment with intravenous corticosteroids again resulted in full resolution within one month.
Clinical timeline and sequential cranial nerve involvement in three representative cases. CN = cranial nerve; CR = complete remission; d = day; Ipsi = ipsilateral; Lt. = left; m = month; PR = partial remission; Rt. = right; y = year.
Figure 2. Long description
The image presents a clinical timeline and sequential cranial nerve involvement in three representative cases of recurrent painful ophthalmoplegic neuropathy. The timeline spans from ages 16 to 64 years and details the progression and remission of symptoms affecting various cranial nerves. Key events include the onset of pain, headache, and remission periods for each patient. The timeline uses color-coded markers to indicate different stages and outcomes, such as complete remission and partial remission. Each case shows the specific cranial nerves affected and the duration of symptoms. The timeline highlights the variability in the sequence and duration of cranial nerve involvement among the patients.
Representative case 2 (Patient 5)
A previously healthy woman developed her first episode of left-sided peripheral facial palsy at the age of 16. Over the subsequent four years, she experienced two additional episodes of facial palsy on the same side at approximately two-year intervals, each preceded by ipsilateral postauricular pain. Each episode was completely resolved within one month after treatment with oral corticosteroids and acyclovir. The patient had a history of intermittent headaches since adolescence, occasionally accompanied by photophobia and phonophobia, but she did not regularly take analgesics.
Approximately seven months after her last episode of facial palsy, she presented with binocular horizontal diplopia for three days. A moderate-intensity dull headache in the ipsilateral periorbital and frontal areas preceded the diplopia by one day, accompanied by photophobia and phonophobia. Neurological examination revealed right abducens nerve palsy. CSF analysis and serologic workup including tumor markers, anti-ganglioside antibodies and autoimmune markers were unremarkable. Brain MRI with gadolinium enhancement revealed focal enhancement in the cisternal space of the right abducens nerve. Following five days of intravenous corticosteroid therapy, the headache rapidly resolved within several days, and the diplopia completely improved within 20 days.
Eight years later, the patient presented again with binocular diplopia. A moderate-intensity dull headache in the same location preceded the diplopia by three days, accompanied by photophobia and phonophobia. Neurological examination revealed a recurrence of right abducens nerve palsy (Supplementary Figure 2). Brain MRI with gadolinium enhancement, CSF cytology and serologic testing were repeated; all findings were unremarkable. Following five days of intravenous corticosteroid therapy, both headache and diplopia resolved completely within one week.
Representative case 3 (Patient 7)
A woman with a more than 20-year history of migraine developed her first episode of left-sided peripheral facial palsy at the age of 54. Her migraines were characterized by pulsatile headaches accompanied by photophobia and phonophobia. They occurred 2–3 times per month and were controlled with analgesics. She also had diabetes mellitus and hypertension. Over the subsequent two years, she experienced two additional episodes of facial palsy on the same side, each preceded by ipsilateral postauricular pain. Each episode was completely resolved within one month after treatment with oral corticosteroids and acyclovir.
At age 61, the patient presented with binocular horizontal diplopia and ptosis. A severe throbbing headache, maximal in the ipsilateral periorbital region, preceded the diplopia by four days and was accompanied by photophobia and phonophobia. Neurological examination revealed partial ptosis; deficits in adduction, supraduction and infraduction; and loss of the pupillary light reflex in the left eye, consistent with left oculomotor nerve palsy (Supplementary Figure 3). CSF analysis and serologic workup including tumor markers, anti-ganglioside antibodies, acetylcholine receptor antibodies and autoimmune markers were unremarkable. Brain MRI with gadolinium enhancement demonstrated no significant abnormalities. Following a five-day course of intravenous corticosteroid therapy, the headache resolved within two weeks; however, the diplopia and ophthalmoparesis persisted.
Diplopia recurred twice over the following three years, at intervals of two years and one year, respectively. In the first instance, the patient developed right abducens nerve palsy preceded by a 10-day ipsilateral dull headache with photophobia and phonophobia; in the second instance, she presented with left abducens nerve palsy preceded by a 6-day ipsilateral dull headache accompanied by photophobia and phonophobia. In both instances, repeat brain MRI, CSF analysis and comprehensive serologic workup revealed no significant abnormalities, and intravenous corticosteroid therapy resulted in complete resolution of symptoms within one month.
Analysis of baseline characteristics and ophthalmoplegic attack features
Including a case previously reported (Patient 1), Reference Kim, Kang, Kang and Lee2 eight patients were enrolled in this study (five females; mean age, 53.3 ± 15.6 years at RPON diagnosis) (Table 1). The mean age at first onset of ophthalmological attack was 49.4 ±16.3 years. Regarding vascular risk factors, three patients had hypertension (37.5%), two had diabetes mellitus (25%) and one had hyperlipidemia. A current or previous history of migraine was identified in five patients (62.5%). The median number of ophthalmoplegic attacks was three per patient (range, 2–5).
Demographic and clinical characteristics of the patients
Table 1. Long description
The table presents demographic and clinical characteristics of eight patients with recurrent painful ophthalmoplegic neuropathy (RPON). It includes columns for patient number, sex, age at attack, vascular risk factors, diagnostic workup, migraine-associated features, attack details, involved cranial nerve, preceding pain or headache, characteristics of pain or headache, focal enhancement on MRI, steroid therapy, and symptom duration. The table has eight rows for individual patients and a summary row at the bottom. Key trends include the predominance of female patients, the presence of vascular risk factors such as hypertension and diabetes, and a history of migraine in over half of the patients. Diagnostic workup consistently includes tests for ganglioside antibodies and various markers. The table details the specific characteristics and treatments for each patient’s attacks.
Ab = antibody; CN = cranial nerve; d = day; DM = diabetes mellitus; F = female; HTN = hypertension; Hx = history; ipsi = ipsilateral; IV = intravenous; Lt. = left; M = male; m = month; N/A = not applicable; N/V = nausea/vomiting; PO = per oral administration; Rt. = right.
Across the 25 total ophthalmoplegic attacks, the abducens nerve was the most frequently involved cranial nerve (15 of 25, 60%), followed by the oculomotor nerve (8 of 25, 32%) and the trochlear nerve (2 of 25, 8%). Preceding headache or periorbital pain occurred in 22 attacks (88%), with a mean interval of 4.0 ± 2.9 days before the onset of ophthalmoplegia. The pain was predominantly localized to the periorbital, frontal or hemicranial regions and was consistently ipsilateral (100%). Abnormal focal enhancement of the involved nerve on brain MRI was observed in two attacks (2 of 23, 8.7%). Most attacks were treated with intravenous or oral steroids, resulting in complete resolution of symptoms and extraocular movement limitations within one week to one month in 92% of cases (23 of 25; mean duration, 19.3 ± 10.9 days).
Analysis of other cranial nerve involvement in RPON
Facial nerve involvement was observed in most participants (7 of 8, 87.5%), with two patients (Patients 5 and 7) experiencing three consecutive recurrent episodes on the same side. One patient (Patient 8) also showed simultaneous involvement of the oculomotor and facial nerves on the same side. Among all 35 cranial nerve palsy events (ophthalmoplegia and facial palsy combined), facial nerve palsy was the second most frequent manifestation (n = 11), following abducens nerve palsy (n = 15). All episodes of facial neuropathy were consistent with peripheral involvement and were accompanied by postauricular pain (Figure 3). Postauricular pain typically occurred 2–7 days before onset, and no migrainous features were reported during these events. Among the cases in which MRI was performed, focal enhancement of the facial nerve was identified in two of three patients (Figure 1A and B). Most facial neuropathy attacks were treated with intravenous or oral steroids, often in combination with acyclovir, and resolved without sequelae within approximately one month (26.4 ± 6.7 days). No involvement of cranial nerves other than the facial nerve was observed in this cohort.
Blink reflex responses in Patient 1 during an episode of facial neuropathy. Blink reflex testing shows that ipsilateral stimulation of the right supraorbital nerve elicits delayed R1 (11.1 ms) and ipsilateral R2 (iR2) (34.7 ms) responses, and the contralateral R2 (cR2) latency is also prolonged (38.8 ms). These findings are consistent with an incomplete type of right-sided peripheral facial neuropathy. Lt. = left; Rt. = right.
Figure 3. Long description
Two line graphs showing blink reflex responses in Patient 1 during an episode of facial neuropathy. The left graph represents left stimulation, and the right graph represents right stimulation. Each graph has two channels, one for the right eye and one for the left eye. The left stimulation graph shows a delayed R 1 response of 9.5 milliseconds and a delayed ipsilateral R 2 response of 30.2 milliseconds. The right stimulation graph shows a delayed R 1 response of 11.1 milliseconds, a delayed ipsilateral R 2 response of 34.7 milliseconds, and a prolonged contralateral R 2 latency of 38.8 milliseconds. The x-axis represents time in milliseconds, and the y-axis represents voltage in microvolts. All values are approximated.
Discussion
The pathophysiology of RPON remains uncertain. Early hypotheses proposed several mechanisms, including mechanical compression of the oculomotor nerve by aneurysms or neurovascular contact and migraine-related arterial swelling that could cause secondary nerve ischemia. Reference Furia, Liguori and Donadio4,Reference Walsh and O’Doherty10 More recently, demyelinating or inflammatory neuropathy has been considered a more plausible mechanism of RPON, supported by observations of focal cranial nerve enhancement on MRI, favorable responses to steroid treatment and time delays of up to 14 days between headache or pain and the onset of ophthalmoplegia. Reference Kim, Kang, Kang and Lee2,Reference Furia, Liguori and Donadio4,Reference Liu, Wang and Bian7,Reference Walsh and O’Doherty10–Reference Smith and Schuster12
However, many patients with RPON still report migrainous headache, and in some cases, ophthalmoplegia developed as the intensity or duration of migraine attacks increased. Reference Furia, Liguori and Donadio4,Reference Liu, Wang and Bian7,Reference Smith and Schuster12,Reference Carlow13 Previous studies have also shown that focal enhancement of the affected nerve on MRI may be present in up to 70% of cases, although other reports, including our series, have found that a substantial proportion of patients show no abnormal MRI findings. Reference Kim, Kang, Kang and Lee2,Reference Furia, Liguori and Donadio4,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Liu, Wang and Bian7
The heterogeneity of clinical manifestations is another important feature of RPON. Compared with traditional descriptions, many patients have shown adult-onset symptoms, frequent involvement of the abducens nerve, preceding headache or pain without migrainous features and normal MRI findings, patterns that were also observed in our cohort. Reference Kim, Kang, Kang and Lee2,Reference Liu, Wang and Bian7 More unusual presentations have been reported as well, such as painless attacks, ophthalmoplegia occurring before headache and bilateral involvement during recurrent episodes. Reference Kim, Kang, Kang and Lee2,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Smith and Schuster12
In our study, three ophthalmoplegic attacks (12%) occurred without accompanying headache or pain. A previous literature review reported that 25% of patients with ophthalmoplegic migraine did not experience headache, eye pain or irritability during their first episode. Reference Smith and Schuster12 Although painless attacks were observed in our cohort, their consistent response to corticosteroid treatment, the presence of ipsilateral preceding headache in most other attacks and negative findings on extensive evaluations support the diagnosis of RPON. However, additional research is needed to clarify whether these atypical presentations fall within the broader heterogeneity of RPON or point to a separate disease entity.
In the literature, RPON has been described primarily as affecting the ocular motor nerves (cranial nerves III, IV and VI). However, a few reports have documented involvement of other cranial nerves, including the trigeminal, facial and hypoglossal nerves, in patients who met the diagnostic criteria for RPON or were considered within its presumed disease spectrum. Reference Kim, Kang, Kang and Lee2,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Hutchinson and Donaldson9 Familial cases have also been described in which recurrent peripheral facial neuropathy and ophthalmoplegia occurred, typically preceded by headache. Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Lee, Brazis and Eggenberger14 In many of these cases, however, headache did not precede ophthalmoplegia consistently, and the characteristics of the headache were not clearly documented, making it uncertain whether those cases truly represented RPON. Reference Lee, Brazis and Eggenberger14 Reports of RPON accompanied by a history of facial neuropathy remain rare. Reference Kim, Kang, Kang and Lee2,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Celebisoy, Sirin and Gokcay15
In a previous case report, we described a patient (Patient 1 in this series) who, during six documented RPON attacks, experienced an episode of seventh nerve enhancement on MRI accompanied by steroid-responsive facial palsy. Reference Kim, Kang, Kang and Lee2 Because the clinical course of this facial neuropathy closely mirrored the pattern observed in the RPON episodes, we suggested that facial neuropathy could represent another possible manifestation of RPON. Reference Kim, Kang, Kang and Lee2 Although it remains uncertain whether facial neuropathy is truly part of RPON or a coincidental finding, all reported cases, including ours, have shown a peripheral pattern and a favorable clinical outcome. Reference Kim, Kang, Kang and Lee2,Reference Gelfand, Gelfand, Prabakhar and Goadsby6,Reference Celebisoy, Sirin and Gokcay15
Facial neuropathy of a uniformly peripheral type, as observed in our series, may indicate infranuclear involvement similar to that seen in other ophthalmoplegic attacks. To evaluate whether these episodes resembled Bell’s palsy, full viral testing was available for one patient (Patient 1). IgM and IgG antibodies for varicella zoster virus and herpes zoster virus, as well as polymerase chain reaction testing for herpes simplex virus–1 and virus–2, were all negative, a pattern also reported in some patients with Bell’s palsy. Reference Zhang, Xu, Luo, Wu, Zhao and Li16 Recurrence of Bell’s palsy is uncommon (6.5%, mean interval 10.2 years) and typically associated with an underlying tumor. Reference Dong, Jung and Jung17 By contrast, two of seven patients with facial neuropathy in our study experienced three sequential recurrences on the same side (28.6%), a pattern more compatible with RPON. Although focal enhancement of the seventh cranial nerve on MRI was observed in some patients, this finding can also be seen in Bell’s palsy and therefore does not reliably distinguish between the two conditions. Reference Kinoshita, Ishii, Okitsu, Okudera and Ogawa18
Taken together, the notably high proportion of facial neuropathy in our series – particularly cases that were recurrent or occurred simultaneously with ophthalmoplegia – suggests that its presence may not be fully explained by coincidence or by migraine-related mechanisms. Ipsilateral pain around the ear and in the face or neck occurs in approximately 33–70% of patients with Bell’s palsy, Reference Berg, Axelsson and Engstrom19 and although its precise mechanism remains unclear, neural anoxia resulting from primary or secondary ischemia and associated inflammation with compensatory vascular dilation has been proposed as a cause. Reference Berg, Axelsson and Engstrom19 Similar to RPON, focal nerve enhancement on brain MRI in Bell’s palsy is typically reversible after the acute phase, raising the possibility that the two disorders may share overlapping inflammatory mechanisms.
THS is one of the representative causes of painful ophthalmoplegia, with reported recurrence rates ranging from 9.7% to 51.6%. Reference Kim, Lee, Lee, Choi and Kim20 In particular, recurrent THS should be carefully differentiated from RPON. Reference Furia, Liguori and Donadio4 According to the diagnostic criteria of the ICHD-3, THS requires granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy. 1 However, previous studies have shown that approximately half of reported THS cases do not demonstrate clear evidence of granuloma on imaging (so-called “benign” THS), and similarities in clinical presentation have been noted between cases with positive and negative MRI findings. Reference Hung, Chang and Wu21–Reference La Mantia, Curone, Rapoport, Bussone and International Headache23 In addition, the favorable response of THS to corticosteroid treatment further complicates differentiation from RPON. Reference Furia, Liguori and Donadio4
Despite these similarities, several distinguishing features have been described. THS typically involves the cavernous sinus, superior orbital fissure or orbit, whereas RPON often shows cranial nerve enhancement within the subarachnoid space on MRI. Reference Kim, Kang, Kang and Lee2,Reference Smith and Schuster12,Reference Kim, Lee, Lee, Choi and Kim20 In THS, involvement of the optic nerve or branches of the trigeminal nerve may occur in addition to the ocular motor nerves, whereas simultaneous involvement of these nerves is very rarely reported in RPON. Reference Kim, Kang, Kang and Lee2,Reference Smith and Schuster12,Reference Kim, Lee, Lee, Choi and Kim20 Even so, differentiating imaging-negative benign THS, particularly in recurrent presentations, from RPON remains a significant clinical challenge.
Conclusion
Our study suggests that facial neuropathy may be more common in RPON than previously recognized. Although coincidence cannot be completely ruled out, the observed patterns in our cohort support the possibility that facial neuropathy represents an additional manifestation within the RPON spectrum. These findings further imply that recurrent inflammatory cranial neuropathy, rather than migraine alone, may contribute to the underlying pathophysiology. Larger studies are needed to validate this hypothesis. In clinical practice, detailed history taking and thorough neurological examination remain essential for identifying involvement of various cranial nerves in patients with RPON.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/cjn.2026.10618.
Acknowledgments
None.
Author contributions
JMK conceived the study, analyzed the data, reviewed the literature, drafted the manuscript and approved the final version. YRK and HLL collected and analyzed the data, critically reviewed the manuscript and approved the final version. SHL conceived the study, interpreted the data, critically reviewed and edited the manuscript and approved the final version.
Funding statement
This study was supported by a grant (BCRI23027) from the Chonnam National University Hospital Biomedical Research Institute. The funding body contributed to data collection and covered the article processing charge.
Competing interests
J.M. Kim, Y.R. Kang, H.L. Lee and S.H. Lee have no conflicts of interest to disclose.
Target article
Facial Neuropathy in Patients with Recurrent Painful Ophthalmoplegic Neuropathy
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