Ophthalmoplegic Migraine

Avery H. Weiss, MD, and James O. Phillips, PhD

Ophthalmoplegic migraine is a rare presentation of migraine complicated by an isolated oculomotor paresis. Vasodilation of extracranial vessels is believed to underlie the headache, and vasoconstriction to account for the ophthalmoplegia. Whether the vascular insult involves the central or peripheral portions of the oculomotor nerve is still uncertain. We describe a child who presented with ophthalmoplegic migraine and was demonstrated to have a deficiency of the near triad documented by eye movement and pupillary recordings. Voluntary conjugate eye movementssaccades, smooth pursuit, and optokinetic nystagmuswere normal. Vergence amplitudes appropriate to fixation distance were elicited for Snellen optotypes but not to a point source of light. Concurrent measures of pupillary diameter failed to reveal significant modulation to either stimulus. Brain magnetic resonance imaging scan was normal, and there was no contrast enhancement of the oculomotor nerve at its exit from the midbrain. Both the oculomotor paresis and concurrent presence of a deficiency of the near triad localized the vascular insult to the oculomotor nerve complex in the brainstem. 2004 by Elsevier Inc. All rights reserved. Weiss AH, Phillips JO. Ophthalmoplegic migraine. Pediatr Neurol 2004;30:64-66.

tudes, and pupillary constriction to accommodative stimuli. To our knowledge, this is the first report of this association. Case Report
A healthy 7-year-old child was observed to have abrupt onset of ptosis and exodeviation of the left eye with horizontal and vertical diplopia. He complained of left supraorbital pain but denied nausea, vomiting, or headache. There were no associated neurologic signs. He was diagnosed with an isolated oculomotor paresis. Pertinent history revealed an ophthalmoplegic episode at age 2 years, which resolved over 2 days. Also he had migraine attacks every 3 to 4 months characterized by listlessness and left supraorbital pain followed by nausea and vomiting which resolved over 1 to 2 days. There was no family history of migraine. Growth and development were age appropriate. Physical examination revealed an alert, comfortable child. There was no proptosis or injection of the left globe. Palpebral fissure height was 9 mm right eye and 4 mm left eye. Motility assessment revealed a 30-diopter (30-D) left exotropia and limited ductions of 25 to 30 in gaze up, in, and down and normal abductions (40). Pupils measured 5 mm in the right eye and 6 mm in the left eye. Pupillary constriction was brisk in the right eye and sluggish in the left eye to direct and consensual light stimulation. Amplitude of accommodation as measured with a Prince rule was 6.6 D. Examination of the anterior and posterior segments was normal. Treatment was not recommended. He returned to the eye clinic 2 weeks later with complete resolution of the ptosis and exotropia at distance, but complained of horizontal diplopia and blurred vision in the left eye at near. Palpebral fissures were symmetric and his eye alignment was normal at distance. However, there was an intermittent 12-D exotropia at near fixation (33 cm). Fusional vergences were reduced at distance (eye alignment breaks with 10-D base out or 8-D base in prism) and at near (eye alignment breaks with 10-D base out or 8-D base in prism). A complete blood count, erythrocyte sedimentation rate, and fasting blood glucose were normal. Magnetic resonance imaging of the brain was performed with head coil, and T1, T2, and fluid-attenuated inversionrecoveryweighted images were obtained in three planes (slice thickness 3 mm). After administration of gadolinium, T1-weighted images were acquired. The images of the brain and brainstem were normal, and no contrast enhancement of the oculomotor nerve at its exit from the midbrain was observed. Several foci of white matter hyperintensity measuring 3 mm or less were identified in the dorsal periventricular region but there was no contrast enhancement. Eye movement and pupillary recordings were performed with binocular infrared video-oculography (Sensomotoric Instruments, Berlin). We recorded version and vergence eye movements, and pupillary diameter in response to visual stimuli. Gaze holding was steady in primary gaze and at horizontal and vertical eccentricities of 15. Pursuit of a point target moving 10 (horizontal or oblique) at 10, 20, and 30/s indicated a normal gain. Acquisition of point targets stepped 5 to 20 (horizontal or vertical) elicited normometric saccades. Horizontal saccades had normal latencies (200-250 ms); vertical saccade latencies were variable (200-350 ms). Horizontal optokinetic nystagmus in response to 0.1 cycles per degree, 100% contrast, square wave luminance gratings drifted at 15/s had normal gain (0.5). Vergence and pupillary diameter were measured in response to a point source of light or accommodative stimulus (Snellen

Introduction Oculomotor nerve palsy is a rare complication of migraine with onset in childhood. [1-3] Although the underlying defect is thought to be vascular, it is unclear whether this is central or peripheral in origin. We describe herein a child with ophthalmoplegic migraine associated with abnormalities of the near triadreduced accommodation, vergence ampli-

From the Division of Ophthalmology, Childrens Hospital & Regional Medical Center, Seattle, Washington.

Communications should be addressed to: Dr. Weiss; Childrens Hospital & Regional Medical Center; Division of Ophthalmology 6E-1; 4800 Sand Point Way NE; Seattle, WA 98105. Received December 31, 2002; accepted June 23, 2003.

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2004 by Elsevier Inc. All rights reserved. doi:10.1016/S0887-8994(03)00424-7 0887-8994/04/$see front matter

optotypes) ramped in the midline to fixation distances ranging from 60 to 15 cm. The accommodative stimuli elicited vergence amplitudes appropriate to fixation distance. By comparison, there were no vergence responses to the point light source. Concurrent measures of pupillary diameter revealed no consistent modulation with changes in fixation distance with either stimulus. On the basis of the history of oculomotor paresis with nausea and vomiting, recurrent presence of an oculomotor paresis, and normal magnetic resonance imaging without contrast enhancement, the child was diagnosed with ophthalmoplegic migraine.

Discussion Ophthalmoplegia is typically an isolated complication of migraine [1-3]. Because a history of head or eye pain may not be elicited in young children, the diagnosis is suspected when there is a history of episodic ophthalmoplegia with nausea, vomiting, and listlessness or irritability. Additional causes of acquired ophthalmoplegia including trauma, tumor, aneurysm, and infiltrative and infectious meningitis, are excluded by the presence of an otherwise normal neurologic examination and the results of brain magnetic resonance imaging [4,5]. Aneurysm is extremely rare in children less than 14 years of age [6]. Neuroimaging evidence of inflammation in the superior orbital apex and cavernous sinus region support a diagnosis of Tolosa-Hunt syndrome. However, proximal enlargement with gadolinium enhancement of the oculomotor nerve within the prepontine cistern has been reported in patients with ophthalmoplegic migraine and Tolosa-Hunt syndrome [7,8]. As gadolinium contrast enhancement is more consistent with inflammation than ischemia, some investigators believe that the magnetic resonance imaging findings support a diagnosis of TolosaHunt syndrome [7,9]. To date, the distinction between these two clinical disorders is blurred when there is proximal oculomotor nerve involvement. The association of oculomotor paresis with reduced strength of the near response can be explained on a neuroanatomic basis. The premotor neurons responsible for the initiation of vergence eye movements and accommodation co-localize to the supraoculomotor area [10,11]. Situated on the dorsal aspect of the oculomotor nuclear complex, the Edinger-Westphal nucleus gives rise to parasympathetic fibers, which join the somatic motor fibers and then diverge to connect with the ciliary ganglion [12]. Postganglionic fibers exiting by way of the short ciliary nerves are then distributed to the ciliary muscle, which regulates accommodation, and to the iris sphincter muscles, which mediate pupillary constriction. However, this area is reciprocally connected to the fastigial and interpositus nuclei of the cerebellum, which are strongly modulated by vergence and accommodation [10,11]. Injections of tracers reveal a bi-directional connection between the supraoculomotor area and the fastigial and interpositus nuclei of the cerebellum. Because of these anatomic relationships, oculomotor paresis or weakened near response, or a combination of both, can result from the same pathophysiology that underlies complicated migraine.

Abnormal vascular reactivity, both vasoconstriction and vasodilation, play a central role in the pathogenesis of migraine. The headaches are believed to result from excessive dilatation of extracranial cerebral arteries, whereas the visual disturbances and neurologic deficits are attributed to vasoconstriction (primary or secondary to compression). Accordingly previous investigators have looked for evidence of vascular abnormalities in ophthalmoplegic migraine. The most commonly cited mechanism is narrowing of the internal carotid artery within the cavernous sinus thereby compromising the blood supply to individual oculomotor nerves [1,13]. Imes et al. reported a vascular anomaly of the posterior cerebral artery in the region of the oculomotor nerve, but its pathophysiologic relationship to the recurrent paresis was uncertain [14]. Friedman et al. reported segmental narrowing of the basilar artery in one patient, but in the remaining cases of basilar artery migraine, vascular constriction was not confirmed by magnetic resonance imaging studies or angiography [2,15]. Alternatively, compression of the oculomotor nerve may result from edema or dilatation of the intracavernous portion of the carotid artery, but arteriograms performed during the attack fail to demonstrate this [16]. Our patient manifested an oculomotor paresis and attenuated near response that cannot be explained on the basis of peripheral nerve involvement. We believe that both neurologic deficits are best explained by a central vascular insult at the level of the oculomotor nerve complex. Consistent with noncytotoxic vascular ischemia or mild cytotoxicity below the threshold for detection by magnetic resonance imaging, there was no enlargement or contrast enhancement of the prepontine portion of the oculomotor nerve.
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[14] Imes RK, Monteiro MLR, Hoyt WF. Ophthalmoplegic migraine with proximal posterior cerebral artery vascular anomaly. J Clin Neuro-Ophthalmol 1984;4:221-3. [15] Lapkin ML, Golden GS. Basilar artery migraine: A review of 30 cases. Am J Dis Child 1978;132:278-81. [16] Vijayan N. Ophthalmoplegic migraine: Ischemic or compressive neuropathy? Headache 1980;20:300-4.

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