Recurrent painful ophthalmologic neuropathy (RPON), previously termed ophthalmoplegic migraine, is characterised by repeated attacks of one or more ocular cranial nerve palsies with ipsilateral headache. Its cause remains unclear; it is currently thought to be neuropathic in origin, but there is debate in the literature. In documented cases, a third cranial nerve palsy is by far the most common. Here we present a case of RPON involving the fourth and sixth cranial nerves only. Thorough investigation, including MR scan of brain and lumbar puncture, found no alternative explanation. This case adds to the debate over whether the cause of RPON is truly neuropathic or migrainous.
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Recurrent painful ophthalmoplegic neuropathy is a rare syndrome characterised by repeated attacks of one or more ocular cranial nerve palsies with ipsilateral headache, in which secondary causes have first been excluded.1 2 Its older name, ophthalmoplegic migraine, appears outdated, particularly since a painful cranial nerve neuropathy is sometimes the cause.1 3 However, we present a case that suggests the older term might still be relevant.
A 26-year-old woman presented to the emergency department with diplopia and several days of headache. She had a 7-year history of similar episodic stereotyped, headaches, involving continuous, moderate intensity unilateral right hemicranial pain. Each would last continuously for several days, with ipsilateral drooping of the right upper eyelid and right eye tearing. There was no photo or phonophobia but she did report nausea, sensitivity to smells and motion sensitivity, but without restlessness or agitation.
This episode began with her typical stereotyped gradual onset headache with ipsilateral autonomic features, but then late on the second day, for the first time, she had diplopia. An ophthalmologist diagnosed a right trochlear and abducens nerve palsy. An MR scan of brain was normal. The headaches resolved over 2 weeks with simple analgesia and the diplopia resolved a few days later, after brief use of ophthalmic prisms.
She was well for 3 weeks but then again developed stereotyped headache; after 1–2 days she again developed diplopia, worse on looking to the right and looking down. On examination, she had a mild non-fatiguable partial right-sided ptosis. The pupils were equal and reactive to light. She had abnormal trochlear and abducens function with slight limitation of right globe abduction and oblique diplopia on looking down. The remaining neurological examination was normal. Blood results were normal, including serum antineutrophil cytoplasmic antibody, Lyme titres and HIV. Imaging was normal, including MR scan of brain, orbit and cavernous sinus with contrast, and MR cerebral angiogram. Lumbar puncture showed normal opening pressure and constituents. We started her on a short course of high-dose corticosteroids and topiramate; the headache resolved within 2 weeks but the ophthalmoplegia took 6 weeks to recover fully.
Recurrent painful ophthalmoplegic neuropathy is rare. It is important first to exclude a secondary cause such as Tolosa–Hunt syndrome, aneurysm, diabetic ocular neuropathy or neoplasm. Table 1 highlights the main differences between recurrent painful ophthalmoplegic neuropathy and its mimics.
In the latest edition of the International Classification of Headache Disorders, the term ophthalmoplegic migraine was rejected, and renamed recurrent painful ophthalmoplegic neuropathy; the classification states that the term ‘migrainous’ is not appropriate, and that the condition is a recurrent painful neuropathy.1 This reflects the findings of focal nerve enhancement or thickening on MR imaging. Moreover, corticosteroid therapy can help some patients. However, the existing evidence is far from conclusive. While cranial nerve thickening or enhancement commonly occurs in children with this condition,4 Lal’s Indian study of adult cases did not replicate this.2 In Gelfand et al’s3 series, corticosteroids helped clearly in only about half the cases; they did not help in our case. Corticosteroids can sometimes help other primary headache disorders including cluster headache and migraine.
Given that the typical headache of recurrent painful ophthalmoplegic neuropathy precedes the ophthalmoplegia, a migrainous cause does seem at least possible. The fact that the headaches are not always fully migrainous in character might argue against a migrainous cause. However, most cases do have migrainous features.3 Typical migrainous headaches last for 4–72 hours without treatment. Some cases of recurrent painful ophthalmoplegic neuropathy fulfil this duration3 although many other cases, including in this patient, last for longer. Status migrainosus is when an otherwise typical migrainous headache lasts for longer than 3 days; it is probably not rare. Vascular complications can rarely follow migraine, for example, migrainous infarction; ischaemia secondary to migraine may be an alternative explanation for the signs and even MR imaging findings in recurrent painful ophthalmoplegic neuropathy. Finally, side-locked migraines can occur in up to 17% of migraineurs.4
Our case was unusual because of the long-standing previous episodes of headaches with migrainous and unilateral autonomic symptoms, lacking only the newer ophthalmoplegic features. The combination of abducens and trochlear nerve without oculomotor involvement in recurrent painful ophthalmoplegic neuropathy is rare.2 Unilateral autonomic features can occur with oculomotor nerve involvement, with ptosis (as in our case) and mydriasis (not in our case), but there was no enhancement of the oculomotor nerve in our case during an attack of ophthalmoplegia (figure 1). Sympathetic dysfunction (Horner’s syndrome) could also explain a partial ptosis, but our case had no miosis and tearing would be atypical. Unilateral autonomic features can be elicited via the trigeminal autonomic reflex. Our patient however showed no clinical or radiological evidence of involvement of this reflex arc (figure 1 includes afferent limb). The unilateral autonomic features described in our case of right-sided ptosis and lacrimation were identical to the many prior episodes she had had of headache without ophthalmoplegia, and are commonly reported in migraine.
Unilateral autonomic features might be elicited via central mechanisms such as hypothalamic activation or activation of the trigeminocervical complex leading to increased sensitivity of an otherwise normal local reflex arc.5 Hypothalamic involvement is also seen in trigeminal autonomic cephalalgias but the classification of these does not fit in with descriptions of recurrent painful ophthalmoplegic neuropathy.
The debate about pathophysiology in recurrent painful ophthalmoplegic neuropathy is not purely academic. Better understanding of its mechanism may better direct treatment. Some cases respond to corticosteroids and some to migraine prophylaxis; some even respond promptly to indometacin.6 However, as yet there are no clear evidence-based treatment guidelines. The existing guidance suggests that recurrent painful ophthalmoplegic neuropathy is a painful cranial neuropathy rather than migraine. However, the available evidence does not justify such a black and white view, and cases such as ours suggest a migrainous component in this rare but important condition.
Recurrent painful ophthalmoplegic neuropathy is a rare but striking neurological condition characterised by unilateral headache with reversible ipsilateral involvement of cranial nerves III, IV or VI.
The diagnosis requires exclusion of alternative causes, such as aneurysm, neoplasm or Tolosa–Hunt syndrome.
Recurrent painful ophthalmoplegic neuropathy was previously called ‘ophthalmoplegic migraine’: our case suggests that the older term might still be relevant; the distinction is not merely academic and may suggest different treatment approaches.
Contributors CH and MA wrote the initial manuscript, which was edited by BL. TY extensively edited the manuscript following the peer review.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Neil Anderson, Auckland, New Zealand.
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