Abstract
The features and management of two adult patients with ophthalmoplegic migraine and longlasting sixth nerve palsies are described. Both had had previous shorter episodes of diplopia following migraine-like headaches. One recovered following an injection of botulinum toxin to the medial rectus of her affected eye 11 months after the onset of diplopia. The other patient had previously had surgery for a consecutive divergent squint and required further squint surgery to realign his eyes 1 year after the onset of his sixth nerve palsy. Both botulinum toxin and squint surgery may be useful in the management of longstanding sixth nerve palsy in patients with ophthalmoplegic migraine. The aetiology of ophthalmoplegic migraine is discussed.
Introduction
Ophthalmoplegic ‘migraine’ is a rare disorder defined as ‘recurrent attacks of headache with migrainous characteristics associated with paresis of one or more ocular cranial nerves (commonly the third nerve) in the absence of any demonstrable intracranial lesion other than MRI changes within the affected nerve’ (1). Although until recently considered an ischaemic microvascular phenomenon related to the migraine (2, 3), more recently swelling and contrast enhancement of the oculomotor nerve have been described in magnetic resonance imaging (MRI) scans from patients with oculomotor ophthalmoplegic migraine. From this evidence it has been considered that the oculomotor nerve pathology is inflammatory and unrelated to migraine (4–6), with reclassification of ‘oculomotor migraine’ as a demyelinating neuropathy (1). Most cases described have involved the third cranial nerve, usually in children, with involvement of the abducens nerve being rare (for example, (7)). Most previous reported cases involving the sixth nerve have recovered within a relatively short period (7–11) and none appears to have required surgical realignment. We report two cases in which a longlasting sixth nerve palsy occurred in adults following an episode of migraine and on their successful management with either botulinum toxin or squint surgery.
Case reports
Case 1
A 36-year-old female initially presented to her local eye department in 1999 complaining of a left-sided dull headache and horizontal diplopia. On examination she had a right convergent squint. She was a longstanding high myope (right eye −14.25/−4.00 × 15, left eye −15.00/−4.00 × 160). Full neuro-ophthalmological examination and investigations, including a lumbar puncture, computed tomography (CT) and MRI scans of the brain, were normal. Her right sixth nerve palsy and associated diplopia resolved spontaneously over a number of months. We have no documentation of the details of the headache in 1999. She presented again in 2001. The referral letter to the hospital stated that the headache had been similar in 1999. On the second occasion she had woken with a right hemicranial headache which she described as a ‘dull’ pain. There was no associated nausea, vomiting, photophobia or phonophobia, but the headache was exacerbated by movement and was of sufficient severity to keep her in bed for that day. She woke the next morning with the headache still present and double vision. The headache persisted for about 3 weeks and the double vision recovered after several weeks.
She then presented with a left sixth nerve palsy associated with a similar headache, which again persisted for 3 weeks. On initial examination she had a marked left esotropia of more than 90 prism dioptres and was unable to abduct the left eye beyond the midline. Eleven months after the start of the episode, the angle of her strabismus had reduced to 30 prism dioptres, but she still had troublesome double vision, although some suppression had developed. She underwent an injection of botulinum toxin into her left medial rectus muscle under EMG control. Four months later, she had a small controlled esophoria (12 prism dioptres) with full abduction, no diplopia and with gross stereopsis (Wirt Fly + ve, indicating a stereoacuity of 3000 s of arc).
Case 2
A 44-year-old man was initially referred to the strabismus service in 2001 for correction of a longstanding right consecutive divergent squint. He had had a right convergent squint as a child, for which he had undergone two previous operations, in addition to glasses and occlusion therapy. His right eye was amblyopic, with a best-corrected Snellen visual acuity of 6/36. His acuity was 6/4 in the left eye. His divergent squint had developed from the age of 16. He largely suppressed his right eye and was troubled by diplopia only when very tired. He underwent an adjustable right medial rectus advancement and lateral rectus recession. Eight months postoperatively he had a cosmetically excellent small convergent squint of 6 prism dioptres for distance and 2 prism dioptres for near with no diplopia.
He gave a history of migraine headaches throughout his adult life. These usually commenced at the right brow and remained localized. The headaches were relieved by simple analgesics and rarely lasted more than 2–3 h. There was no associated nausea, vomiting, photophobia, phonophobia or dysautonomic features and no exacerbation by movement. Once or twice in a year he would experience a similar but more severe headache associated with photophobia and phonophobia accompanied by diplopia, which would last for a matter of hours only.
Fourteen months after the strabismus surgery, in 2002, he had an attack of migraine which commenced in the right periorbital region and spread to become right hemicranial. He described this headache as being the most severe he had ever experienced. There was associated photophobia and phonophobia and nausea. The severe headache lasted for 2–3 days and was followed by a mild headache lasting 4–5 days. It was during the second period of mild headache that he developed diplopia whilst driving and presented again to us. On examination, he had a constant large right convergent squint of 55 prism dioptres, with horizontal diplopia and limitation of right abduction. Ocular examination and the cranial nerves were otherwise normal. An MRI scan of the brain and orbits showed no abnormality and his blood tests were normal. It was concluded that his right lateral rectus weakness was related to the severe migraine attack. One year after the migraine attack he was still convergent with troublesome diplopia, presumed to be because his right eye had moved out of its suppression area. He therefore underwent an adjustable right medial rectus recession and lateral rectus advancement. Postoperatively, he was slightly convergent (4 prism dioptres for distance and 8 prism dioptres near) with some diplopia present for near only. However, it was noted that his near vision was reduced and that a +1.00 dioptre lens placed before each eye reduced the convergence of the eyes and eliminated the diplopia. A pair of +1.50 dioptre reading glasses eliminated his symptom of diplopia.
In 2005 he had a second attack of severe headache followed by a right lateral rectus paresis essentially similar to that described in 2002.
Discussion
Ophthalmoplegic migraine is a rare condition, with an incidence of approximately 0.7 per million (7). It is more common in infancy and childhood, with a male predisposition (11). In ophthalmoplegic migraine, the nerve palsy usually occurs during or within a few days (1–7 days) of the migrainous episode (3). The commonest ocular motor paralysis occurring is a total or partial oculomotor nerve palsy, with involvement of the sixth nerve being less common (3). Hansen et al. have described eight cases with ophthalmoplegic migraine, with the oculomotor nerve being affected in seven patients and one patient having an isolated abducens nerve palsy (7).
This paper describes two patients with longlasting sixth nerve palsies following a migrainous episode. Ophthalmoplegic migraine involving the sixth nerve is rare and there appear to be no previous reports of patients with this condition being treated with either botulinum toxin or squint surgery. It is possible that the first patient would have eventually recovered without botulinum toxin, as the angle of her squint had decreased prior to her receiving this treatment. Evidence from the treatment of acute sixth nerve palsies with botulinum toxin is that it gives symptomatic relief, but does not improve long-term outcomes (12, 13). However, most of these were acute palsies, which typically recover within 3 months of onset, whereas the present patient still had a manifest deviation 11 months after the onset of symptoms. Botulinum toxin has previously been shown to produce a longlasting recovery of binocular function in some patients with a longstanding deviation (14).
Interpretation of the findings in the second patient is complicated by his pre-existing squint with suppression of vision in the affected eye. Following his first squint operation as an adult for consecutive divergence, his eyes were well aligned, with his deviating eye being aligned within his suppression scotoma so that he had no diplopia. Following his sixth nerve palsy, he became markedly convergent with an abduction deficit and experienced diplopia because his affected eye had moved out of its suppression area. He showed no recovery of alignment by 1 year and so underwent a further squint operation. This, together with the use of reading glasses to reduce his convergence for near, realigned his eye to within his suppression area, with abolition of his diplopia. Whether his longstanding lack of binocularity impeded the recovery of his alignment is an interesting point, since his abduction did recover.
Ophthalmoplegic migraine had been considered to have a microvascular, ischaemic aetiology (2, 3), but more recently it has been reclassified as a demyelinating condition affecting the oculomotor nerves (1) because of the demonstration of swelling and enhancement of the intracisternal portion of the third nerve on CT or MRI scanning in affected patients (5). However, it is difficult to see how a primary demyelinating lesion restricted to the sixth nerve could cause the 3 days of severe headache, photophobia, nausea and visual disturbance associated with the onset of the sixth nerve palsy in the second patient and in those described, for example, by Celebisoy (8). A localized ischaemic event has been shown pathologically to cause localized demyelination in the third nerve (15) and localized retinal ischaemia is well recognized to cause localized axoplasmic holdup in the retina in the form of cotton-wool spots, both in migraine (3) and in other conditions such as diabetic retinopathy. A microvascular occlusion can thus cause both focal demyelination and axoplasmic holdup. Patients with migraine are at increased risk of vascular occlusion affecting the brain (16), optic nerve head in anterior ischaemic optic neuropathy and in glaucoma, and central retinal artery occlusion (3). It seems more likely that the longlasting sixth nerve palsies described here were microvascular in origin rather than from inflammatory demyelination. Although the third nerve palsies described in ophthalmoplegic migraine may be different, it is of interest that the swelling and enhancement described in oculomotor migraine were intracisternal, whereas inflammatory third nerve lesions in general affect both intracisternal and more anterior regions of the third nerve (17).
The time course of onset and recovery of persistent third and sixth nerve palsy associated with migrainous sounding headaches closely resembles that seen after ischaemic microvascular palsies associated with diabetes and hypertension (18). The difference in ophthalmoplegic migraine is the stereotypical nature of the attacks, with often the same nerve on the same side being affected repeatedly. However, the question of aetiology can be resolved only by further observation.