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

Abstract

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.

Introduction

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder characterized by repeated unilateral headaches and associated ipsilateral paresis of the ocular motor cranial nerves (1). In the third edition of the International Classification of Headache Disorders (ICHD-3), the terminology of ophthalmoplegic migraine (OM) was replaced by RPON based on the fact that the headache may develop up to 14 days prior to oculomotor paresis, gadolinium enhancement or nerve thickening can be demonstrated on magnetic resonance images (MRIs), and treatment with corticosteroid is beneficial in some patients.

In RPON, the oculomotor nerve is more commonly involved than the trochlear or abducens nerve (2). The symptoms of RPON are usually present for a few weeks with a full recovery during each episode (3). Accordingly, persistent ophthalmoplegia rather suggests other organic lesions involving the ocular motor cranial nerves.

In RPON, enhancement of the ocular motor cranial nerves could be seen in the cisternal segment during the acute phase, and the enhancement usually resolves within 12 weeks after recovery from the symptoms (4–6). However, patients with the features of RPON may show persistent enhancement of the ocular motor nerves even after resolution of the symptoms, and have been found to have tumors (7–11). We report two patients whose MRI findings are compatible with an oculomotor nerve schwannoma who initially presented with RPON, and reviewed the literature on ocular motor cranial nerve tumors that masqueraded as RPON.

Methods

We report our two patients with MRI findings of oculomotor nerve schwannoma that mimicked RPON, and reviewed the literature on ocular motor cranial nerve tumors masquerading as RPON. The literature search was conducted using PubMed (up to June 2014). The following keywords were used: recurrent painful ophthalmoplegic neuropathy, ophthalmoplegic migraine, oculomotor nerve tumor, trochlear nerve tumor, abducens nerve tumor and oculomotor schwannoma. We included all the patients described in case reports published in English. All potential references that were cited in these articles were also reviewed.

Report of patients

Patient 1

A 31-year-old woman presented with binocular diplopia and right ptosis for 30 days. One month earlier, she had suffered from acute headache in the right temporal area. The headache improved two days later, but then ophthalmoplegia and ptosis developed in the right eye. She had a five-year history of recurrent migrainous headaches associated with right oculomotor nerve palsy. The attacks tended to occur twice a year. The headaches had always been throbbing in the right temporal area. The headaches were associated with nausea and vomiting, and would last about a day. The ophthalmoplegia accompanied by headaches usually resolved within two weeks without particular treatments. This time, however, the ophthalmoplegia had persisted without improvement for a month until she was admitted to the hospital.

Examination showed right ptosis and limitations of eye motion except abduction in the right eye. The palpebral fissure measured 4 mm in the right eye and 10 mm in the left eye (Figure 1). The right pupil was dilated at 5 mm without a response to light and accommodative stimuli, while the left pupil measured 3 mm with normal reflexes. Other findings of neurological and neuro-ophthalmological examinations were normal.

Figure 1.

Nine gaze photographs of patient 1 show ptosis and limitations of eye motion except abduction in the right eye on admission.

The MRIs taken during the last attack revealed a 3-mm enhancing nodule on the cisternal segment of the right oculomotor nerve (Figure 2). She received intravenous methylprednisolone 1000 mg per day for five days that was followed by oral prednisolone 30 mg per day. The ophthalmoplegia partially improved after the steroid pulse therapy. The oral prednisolone was kept on for eight more months because of an incomplete recovery of the opthalmoplegia. Follow-up MRIs eight months after the onset of the last attack still showed the nodular enhancing lesion involving the right oculomotor nerve without a significant interval change (Figure 2). The follow-up examination one year later still showed an incomplete recovery of the ophthalmoplegia along with ptosis in the right eye.

Figure 2.

During the acute phase, MRIs (3.0 T, Vision, SIEMEN S (a–c)) show a 3-mm nodular enhancing lesion in the cisternal segment of the right oculomotor nerve (arrows). Follow-up MRIs (d–f) during the quiescent phase eight months later still demonstrate an enhancing lesion without a significant interval change (arrows). MRI: magnetic resonance images.

Patient 2

A 52-year-old man was referred for evaluation of headache and binocular diplopia. Three days earlier, he had developed severe pulsating headache in the right parietal area accompanied by ophthalmoplegia and ptosis in the right eye. He had a history of four headache attacks that had accompanied a complete right oculomotor palsy with a resolution within a week after steroid pulse therapy. The headaches were mostly throbbing in the right parietal area with a moderate intensity and associated nausea and vomiting. Those headaches would last about 24 hours. Findings of neurological examination had been reported to be normal between the attacks.

Examination during this attack showed ptosis and limitation of all ductions except abduction in the right eye (Figure 3). The palpebral fissures measured 2 mm in the right and 8 mm in the left eye (Figure 3). The right pupil was enlarged at 5 mm without a response to light and accommodative stimuli. The responses of the left pupil were normal. Other findings of general physical and neurological examination were normal.

Figure 3.

Nine gaze photographs of patient 2 show ptosis and limitations of eye motion except abduction in the right eye on admission.

MRI showed a 3-mm nodular enhancing lesion on the cisternal segment of the right oculomotor nerve (Figure 4). The patient received intravenous methylprednisolone 1000 mg per day for five days, which was followed by tapering of oral prednisolone over the next two months. The headache resolved a day after the initiation of the steroid pulse therapy. However, unlike in the previous events, recovery of the ophthalmoplegia was incomplete, and follow-up examination 10 months later showed the right pupil still enlarged at 5 mm without a response to light and accommodative stimuli and a mild right ptosis in the presence of normal ductions. Follow-up MRIs one year later showed a still enhancing nodule on the right oculomotor nerve without a significant interval change (Figure 4).

Figure 4.

During the acute phase, MRIs (3.0 T, Vision, SIEMENS (a–c)) show a 2-mm nodular enhancing lesion (arrows) in the cisternal segment of the right oculomotor nerve. Follow-up MRIs (d–f) during the quiescent phase 12 months later still exhibit an enhancing nodule (arrows) without a significant interval change. MRI: magnetic resonance imaging.

Literature review

Through the literature search, we could find five well-described cases of ocular motor cranial nerve tumors that masqueraded as RPON (Table 1). Of interest, all affected the oculomotor nerve and no cases were found to involve the trochlear or abducens nerve.

Table 1.

Clinical findings in the patients with oculomotor nerve tumors masquerading recurrent painful ophthalmoplegic neuropathy.

Authors	Age/Sex	Duration of headache	Involved nerve	Involved portion	Diagnosis
Kawasaki et al. (1999)11	23/F	16 years	Oculomotor, Rt	Cisternal	Schwannoma
Berbel-Garcia et al. (2004)9	18/F	1 year	Oculomotor, Lt	Cavernous sinus	Venous angioma
Murakami et al. (2005)7	11/F	5 years	Oculomotor, Lt	Cisternal	Schwannoma
Bisdorff and Wildanger (2006)8	14/F	12 years	Oculomotor, Rt	Cisternal	Schwannoma
Akimoto et al. (2012)10	51/M	45 years	Oculomotor, Lt	Cisternal	Neuromuscular harmatoma
Kim et al. (2014)a	52/M	10 years	Oculomotor, Rt	Cisternal	Schwannoma
	31/F	5 years	Oculomotor, Rt	Cisternal	Schwannoma

^aCurrent study. Rt: right; Lt: left; F: female; M: male.

Including ours, five patients were women and two were men with ages ranging from 11 to 52 years (mean ± SD 28.5 ± 13.8 years). The mean duration from the initial migrainous headaches to the final assessment was 13.4 ± 9.8 years (range 1–45 years, median = 10 years).

MRIs with gadolinium enhancement were completed in all patients and 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. The remaining patient showed a high-velocity signal loss with flow-related enhancement in the cavernous sinus, which was confirmed as a venous angioma with cerebral angiography. Overall, the radiological or pathological (n = 4) diagnosis included schwannoma in five, venous angioma in one, and neuromuscular harmatoma in another one.

Discussion

We report two patients whose MRI features are compatible with the oculomotor nerve schwannoma that mimicked RPON (8). Like the typical cases of RPON, our patients showed a complete recovery of ophthalmoplegia and ipsilateral headaches during the first several attacks. However, the following attacks were characterized by an incomplete recovery of the ophthalmoplegia and the persistently enhancing nodule without an interval change on follow-up MRIs.

In RPON, the ophthalmoplegia generally lasts only for days to weeks after remission of the headache and recovers completely. Previously, only a few studies reported a persistent ophthalmoplegia in pediatric patients with RPON and no structural lesion (12–15).

In RPON, enhancement of the ocular motor cranial nerves could be seen in the cisternal segment only during the acute phase, and this enhancement usually resolves within 12 weeks after recovery of symptoms (4–6). Thus the incomplete recovery of ophthalmoplegia in our patients appears strongly related to the persistently enhancing nodules in the oculomotor nerve, which were diagnosed as schwannoma radiologically. Indeed, there have been several reports on various tumors involving the oculomotor nerves that masqueraded as RPON (7–11,16).

However, the mechanism of intermittent unilateral headaches and ipsilateral ophthalmoplegia remain speculative in these cases. Intermittent release of a chemical substance from the tumors and resultant stimulation of the trigeminal nerve receptors have been proposed as a mechanism of migrainous headache (7). Another hypothesis involves repeated inflammation leading to demyelination and remyelination with a potential to change into schwannoma from schwann cell proliferation (17). In our patients, the later development of incomplete recovery and persistent enhancing nodule are suggestive of the latter hypothesis as a more probable explanation of the attacks. However, serial follow-ups of MRIs in patients with uncomplicated RPON seem mandatory to prove this explanation.

In conclusion, clinicians should be aware of the possibility of an incomplete recovery 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.

Clinical implications

Oculomotor nerve tumors may masquerade as recurrent painful ophthalmoplegic neuropathy (RPON).

Clinicians should be aware that an incomplete recovery may occur during future attacks in patients with otherwise uncomplicated RPON.

Follow-up magnetic resonance images (MRIs) are required to detect tumors involving the ocular motor cranial nerves in patients with suspected RPON when the recovery is incomplete.