Abstract
Ophthalmoplegic migraine (OM) had been classified as a form of migraine by the Headache Classification Committee of the International Headache Society in the 1988 classification (1). The classification was revised by the same committee in 2004 and OM was classified under the heading of ‘Cranial neuralgias and central causes of facial pain’ and was defined as consisting of at least two episodes of headache accompanied or followed within 4 days of its onset by paresis of one or more cranial nerves: third, fourth and/or sixth with appropriate investigations having excluded paracellar, orbital fissure and posterior fossa lesions (2). Hansen et al. (3) estimated an annual incidence of 0.7 per million. Although it may have onset at any age, it occurs most frequently in infants and children under 12 years of age. The headache is unilateral and invariably ipsilateral to the side of ophthalmoplegia. It is typically severe and may precede the ophthalmoplegia by several days. In OM there is a predilection for males whereas the preponderance of persons with common migraine is female (4). We report two unusual cases: two women with probable OM, one having an onset at age 16 years and the other at 50, both with abducens palsy.
Case reports
Case 1
A 22-year-old girl was seen for the first time with right unilateral pulsating retroorbital headache on the right side. The headache was followed within 24 h by horizontal diplopia. She had no nausea or vomiting, but photophobia. She had experienced a right-sided peripheral facial palsy 3 months ago which had resolved incompletely. She had had four previous attacks accompanied by headache and right-sided abducens palsy in 1997, 1999, 2001 and 2002. In all the attacks the abducens palsy had occurred within 24–48 h after the appearance of the headache and lasted for 1–3 weeks. Apart from those attacks she had had no aura or headache. Her past medical history was unremarkable except for the above-mentioned disturbances. When she was seen on the second day, she had right-sided abducens palsy and a right-sided sequel peripheral facial paresis. The retroorbital headache subsided within 4 days, but the abducens palsy lasted for 2 weeks. Her complete blood count, blood biochemistry and cerebrospinal fluid (CSF) examination including protein, glucose levels and cell count were in normal range. Contrast-enhanced and non-enhanced 1.5-T axial, coronal and sagittal T1- and T2-weighted magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) were also normal.
Case 2
A 51-year-old woman was admitted to hospital because of diplopia which developed after a 3-day bout of left-sided pulsating severe headache localized to her left frontal, retroorbital region. She had nausea, vomiting and photophobia. The headache had subsided after the appearance of the diplopia and ended on the fifth day. She was neither hypertensive nor diabetic and did not smoke or use alcohol. She had had similar attacks of headache for 10 years, recurring approximately every 3–4 months, always localized to the left frontal, retroorbital region and lasting for 3–10 days, accompanied by photophobia, nausea and vomiting. She had experienced another attack with diplopia a year ago. Diplopia had developed on the fourth day of throbbing left retroorbital headache and lasted for 2 weeks. She had been investigated for that attack by MRI with normal results and was diagnosed as having migraine and was given eletriptan which gave good relief. Apart from a left-sided abducens palsy her examination was normal. Complete blood count, blood chemistry including HbA1c and oral glucose tolerance tests were normal. CSF examination was normal including protein, glucose levels and cell count. Contrast-enhanced and non-enhanced 1.5-T axial, coronal and sagittal T1- and T2-weighted MRI of the brain was normal as well. The abducens palsy lasted for 3 weeks and she returned completely to normal at the end of this time.
Discussion
The first attack of OM is commonly seen in infancy or childhood. Our first patient was aged 16 and our second was 50 years old when their first attack had occurred. In our second patient headache episodes always localized to the left retroorbital and frontal region and had started at age 40, but she experienced the first ophthalmoplegia episode associated with the headache at 50 years old. Verhagen et al. presented a 44-year-old woman with recurring left-sided abducens palsy preceded by severe ipsilateral pulsating pain behind the eye and resolving completely in 3 weeks to 2 months. All her laboratory examinations including CSF, contrast-enhanced and non-enhanced cranial MRI and MRA were normal (5). Lee et al. (6) presented a woman aged 42 years who had headache attacks meeting the criteria of migraine. However, no other patient having an onset at such an age could be found. The other interesting factor concerning our patients is the involvement of the abducens nerve, which is very rare. Donahue (7) reviewed 1600 cases of migraine and found diplopia in 14%, which is higher than the more recent reports. Isolated abducens nerve palsy was seen in seven cases (0.4%).
In our first patient an ipsilateral peripheral facial paresis had preceded the last ophthalmoplegia attack. Two patients diagnosed as Tolosa–Hunt syndrome (THS) have been reported in whom facial palsy preceded ophthalmoplegia (8) but there are no reports about the association of OM and facial paresis. The similarity of symptoms to those of THS has encouraged speculation that OM may be a variant of this disorder. The only differentiating feature depends on the finding of granulomatous lesions in the cavernous sinus, by either radiological or pathological methods, in THS (9). In none of our patients was a cavernous sinus pathology seen on MRI with gadolinium.
Diabetic ophthalmoparesis can produce clinical conditions similar to those of OM but none of our patients was diabetic and their blood biochemistry (including HbA1c and oral glucose tolerance tests in the second patient) were in the normal range.
The aetiology of OM is still unclear. A definitive study by Mark et al. (10) included six patients studied by MRI in the acute phase who all showed intraneural enhancement with enlargement of the oculomotor nerve at the point where it emerges from the midbrain and extending along the proximal course of the nerve. Such uptake is seen in the facial nerve in Bell's palsy (11) and in idiopathic trigeminal sensory neuropathy (12). This finding prompted some authors to propose that either a viral or non-infectious, inflammatory origin might be part of the pathogenesis of OM (10, 13). Lance and Zagami (14) proposed that the pain associated with the recurrent ophthalmoplegia was due to irri-tation of the trigeminal sensory fibres because of the inflammatory process affecting the oculomotor nerve. This would subsequently activate the trigeminovascular system in those who are already migraineurs, thereby triggering the associated migraine headaches (14). This hypothesis depends on the finding that in primates and other species, sensory fibres from the ophthalmic division of the trigeminal nerve enter the oculomotor nerve, pass through it into the brainstem and terminate in the spinal trigeminal nucleus (15).
We found no abnormality of the abducens nerve or the brainstem in our patients’ enhanced MRI studies which were performed when the abducens palsies were persisting. Thickening and MRI contrast enhancement of the abducens nerve itself has not been described in OM with abducens palsy (5). On the other hand, almost all cases with OM and oculomotor nerve palsy studied with MRI have shown the enhancement of the nerve in its cisternal portion (10, 13). A single case involving only the superior branch of the third nerve did not enhance (16). Another case with a fourth nerve OM also had no enhancement (17). Thus, there is not the same enhancement of the root of the sixth nerve in OM as there is of the third nerve in OM. This means third-nerve OM is convincingly a cranial neuralgia whereas sixth-nerve OM is still enigmatic and uncertain.
We presented two women, one young and the other middle aged, who were diagnosed as having OM with abducens palsy by excluding other possible conditions. None of them had contrast enhancement of the nerve on MRI during the acute attack.