In this rare variety of complicated migraine the headaches are associated with ocular motor nerve palsies.{85,86} Usually the ophthalmoplegia is transient; however, it can become permanent especially after repeated attacks. Major controversy has surrounded the diagnostic and nosologic position of ophthalmoplegic migraine since its initial recognition in the mid 1880s. A detailed review of the early history of the disorder is admirably presented by Bruyn.{66} Until the l930s and 1940s when angiography was introduced and practiced, it was impossible in many cases to rule out aneurysms and other lesions in the vicinity of the cavernous sinus. Multiple etiologies were cited as underlying causes of "ophthalmoplegic migraine," including aneurysm, basilar arachnoiditis, and tumors; indeed, many physicians believed that no separate clinical syndrome of ophthalmoplegic migraine existed, but that all patients had specific organic lesions.

As pointed out by Walsh and Hoyt,{43} "at the root of the problem has been a lack of strict criteria for the clinical diagnosis of ophthalmoplegic migraine and insufficient knowledge of the pathophysiologic events that occur during a migraine attack." Walsh and O'Doherty{87} presented specific criteria for the diagnosis of the syndrome:
1. A history of typical migraine headache, ie, a severe throbbing headache usually unilateral, but occasionally bilateral or alternating. It is typically of the crescendo type and may last several hours or days.
2. Ophthalmoplegia including one or more nerves and possibly alternating sides with attacks. Extraocular muscle paralysis may occur with the first attack of headache or, rarely, precede it. However, the paralysis usually appears subsequent to an established migraine pattern.
3. Exclusion of other causes by arteriography, surgical exploration or autopsy.
Alpers and Yaskin{75} presented the case of a patient with this clinical syndrome, who had no organic lesion found at autopsy. Additional cases which fulfill all the clinical criteria for ophthalmoplegic migraine have been recorded.{88-90}
In a review of 5,000 migraine patients, Friedman et. al.{91} found 8 patients with ophthalmoplegic migraine, thus attesting to its rarity. All 8 patients (5 male and 3 female) had periodic migraine headaches and unilateral ophthalmoplegia. Three patients had persistent ophthalmoplegia after years, and 1 had a definite family history of migraine. Six patients had arteriograms during the attacks; all results were normal. The details of this review are listed below:
Number of attacks: 4 patients with 20+ attacks; 2 patients with 5 to 10 attacks; 2 patients with less than 5 attacks; and 1 patient with a single attack. Age at onset: 2, 2, 3, 3, 5, 8, 17, and 30 years. Clinical findings: Oculomotor paresis in all; pupillary involvement in 7. Pain: Always on the same side as ophthalmoplegia. Paresis: Occurred 3 to 5 days after onset of headache in 6 patients. Recovery: 1 to 4 weeks. Arteriogram: Normal in attack in 6 of 6. Therapy: Limited success.
In most patients with well-defined cases the onset of ophthalmoplegia occurs before age 10. Woody and Blaw{92} reported two cases of ophthalmoplegic migraine occurring in infants five and seven months old. The infants had recurrent attacks with almost complete clearing between episodes. Both children were treated with prednisone during subsequent attacks which seemed to shorten the duration of the episodes.
In ophthalmoplegic migraine the third nerve is most frequently involved. Walsh and Hoyt{43} state that abducens palsy occurs 1:10 as frequently as third nerve palsy, with even rarer affliction of the fourth nerve. In most cases positive family history is not present. Thus, a typical clinical syndrome emerges: a child or young adult with periodic headache has ophthalmoplegia involving all functions of the third nerve, beginning at the height of an attack of cephalgia, which is primarily unilateral and in the orbital region; the paresis lasts for days to weeks following the cessation of headache; recovery is gradual and tends to be less complete after repeated attacks. The following case report is considered exemplary:

A 3-year-old boy presented with a complete left oculomotor palsy. The day before he had complained of headache, was lethargic, and went to bed early. The following morning he awakened with complete ptosis of the left upper lid, but his headache was gone. On examination the left pupil was 6 mm and slightly reactive to light; all muscles supplied by the left third nerve were profoundly affected.
Figure 10. Third nerve palsy, child unable to look up.
The neurologic examination and plain skull x-rays were entirely normal. The child recovered completely in 3 weeks' time. An exactly similar episode occurred 20 months later, also with rapid spontaneous resolution, and a third episode occurred 1 year after that. The child is now well and suffers only occasional headaches.

In the differential diagnosis, consideration should be given to aneurysm, tumor, diabetes, and sphenoid sinus mucocele. The age at onset, negative glucose tolerance test, and radiologic studies will usually rule out the listed possibilities. Other clinical entities confused with ophthalmoplegic migraine have included myasthenia gravis and the Tolosa-Hunt syndrome. The former condition is ruled out if the pupil is involved (and actually should not be considered in the presence of pain) and with response to edrophonium chloride (Tensilon); the latter possibility should be considered if pain persists. On rare occasions only limited involvement of the third nerve occurs.
Reports of transient, otherwise unexplained unilateral pupillary mydriasis have been tentatively attributed to migraine in young patients.{93-95} One should be careful to exclude intermittent angle-closure glaucoma with mydriasis as pointed out by Sarkies and colleagues.{96} They reported a 31 year old man with an 18 month history of episodic periorbital pain who, during an attack, noted blurred vision and a dilated pupil. He was found to have a sector palsy in the upper nasal quadrant of the left iris, an intraocular pressure of 16 mm Hg between attacks and on gonioscopy and narrow angle with a plateau-type iris. During an attack his intraocular pressure increased to 26 mm Hg. Following a provocative dark-room test, the patient developed a typical headache and was found to have an intraocular pressure of 45 mm Hg and a closed angle on gonioscopy. This report is important because it points out a condition which must be eliminated before considering episodic mydriasis with ocular pain to be a part of ophthalmoplegic migraine.
Rarely, ophthalmoplegic migraine may occur without headache. Durkan et al{97} described two children with isolated recurrent painless oculomotor palsy in whom neurodiagnostic investigations were all normal.
In the differential diagnosis, suspicion would be raised by 1) the absence of a migraine history; 2) severe persistent headache with total ophthalmoplegia; 3) onset after age 20; and 4) symptoms and signs of subarachnoid hemorrhage. Angiography is not warranted in a young patient strictly fulling the clinical criteria.
Now, however, this is a diagnosis of exclusion, and noninvasive imaging tests such as magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA) should be performed in all cases to exclude the possibility of aneurysm.{86} The finding of an entirely normal MRI in a child with a third cranial nerve palsy following a 4 day history of headache, who is otherwise well, should complete the workup. This is because aneurysmal third nerve palsies are extremely rare in children under age 14 years.{98} However, in third nerve palsy involving pupillomotor function, serious consideration should be given to angiography. The usual cause will be a posterior communicating artery aneurysm, which is best excluded by conventional angiography. However, newer techniques such as MRA or spiral contrast-enhanced computed tomographic scanning may soon provide sufficient resolution to exclude aneurysm as a cause.{86}
The pathophysiology of ophthalmoplegic migraine remains obscure. Theories include swelling of the posterior cerebral artery, pituitary swelling, vascular anomaly with compression of the third nerve, and unilateral brain swelling. None of these theories has been documented, and cerebral angiography is unrevealing. Walsh and O'Doherty{87} suggested that a swollen intracavernous carotid artery compressed adjacent cranial nerves within the cavernous sinus. Such swelling would also narrow the vessel, which they attempted to document angiographically. However, subsequent negative arteriograms during attacks do not support this theory.{91} In Nigeria, ophthalmoplegic migraine has been associated with an abnormal hemoglobin.{99}
Ideally, prophylactic therapy would prevent the occurrence of repeated episodes and prevent the development of permanent eye muscle palsies, but reports suggest that therapy has met with only limited success.{91} A trial with calcium channel blocking drugs such as verapamil or beta blocking drugs such as propranolol or even methysergide may be warranted if the attacks are frequent. However, given the fact that this entity is probably similar to Bell's palsy one now ( 2001 ) consider initial treatment with steroids and perhaps antiviral agents such as famcyclovir.