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Opthalmoplegic Migraine / Recurrent Painful Ophthalmoplegic Neuropathy

HomePediatric Ophthalmology and Strabismus / Special Forms of Strabismus
Title: Opthalmoplegic Migraine / Recurrent Painful Ophthalmoplegic neuropathy
Date: 09/2015
Keywords: Opthalmoplegic Migraine, Recurrent Painful Ophthalmoplegic neuropathy

Brain MRI T-1 with contrast axial cut

Brain MRI T-1 with contrast axial cut

Brian MRI T-1 with contrast coronal cut

Brian MRI T-1 with contrast coronal cut

Case Report:

Chief Complaint: Lid drooping and drifting eye

History of Present Illness: 3 year 3month old girl with past medical history of oculomotor nerve palsy (episode 2 years prior, resolved) presents with recurrent symptoms of oculomotor palsy. Four days prior, she experienced a GI illness with vomiting and decreased energy. Her parents deny fever, upper respiratory infection, cough, eye pain, rash or HA. The GI illness resolved two days later and around the same time her right upper eyelid began to droop. Over the next two days the drooping progressed and the patient developed deviated eye and asymmetric pupils. Her previous episode of oculomotor nerve palsy developed much like the present one. The parents report a sub-acute onset over a few days that progressed from ptosis, to anisocoria and strabismus. The episode resolved without treatment over about one week. An MRI was performed at an outside hospital and the read was as follows: “Enhancement of the right third cranial nerve which is most prominent immediately adjacent to the origin of the nerve at the brain stem. The enhancement extends anteriorly along the nerve to the cavernous sinus.” Her clinical presentation and imaging were felt to be consistent with inflammatory neuritis, most likely post viral.

Past Medical History: Otherwise non-contributory

Past Surgical History: None

Medications: None

Allergies: No known drug allergies

Immunizations: Up to date

Development: Age appropriate

Family History: No family history of eye disease, migraine, MS, neurologic disease, childhood cancers. Maternal cousins with celiac disease and DM1

Social History: Lives with parents; 2 cats and a dog. Attends daycare

Review of Symptoms: All negative except as above

Ocular Physical Exam:

Vital signs and labs:

Image 1: Axial MRI T1 with contrast showing enhancement of the right 3rd nerve in the cisternal segment.
Image 2: Coronal MRI T1 with contrast showing enhancement and thickening of the cisternal portion of the right oculomotor nerve.


Case Discussion:
Based on clinical presentation, the list of differential diagnoses for our patient’s third nerve palsy would be quite extensive. ADEM and Miller-Fischer syndrome can present as third nerve palsies but they would also tend to be accompanied by other neurologic deficits such as ataxia or areflexia. When the recurrent and resolving history is taken into account aneurysm, schwannoma, TB, Lyme, sarcoid, and lymphoma become less likely as these would tend to be slowly progressive and unlikely to resolve without treatment. Imaging confirms the absence of schwannoma and also rules out Tolosa-hunt which would show inflammation in the cavernous sinus and meningeal enhancement. Aneurysm, Tolosa-Hunt, and Miller-Fisher syndrome would also be quite rare in this age group.
With all of these factors taken together the most likely diagnosis is either post-viral neuritis or Ophthalmoplegic migraine/Recurrent painful ophthalmoplegic neuropathy (OM/RPON). It is possible that these two conditions are related.

OM/RPON is a rare condition with a prevalence of 0.7 per million6; it usually begins in childhood.2,3 A systematic review authored by Gelfand found a median age of onset at 8 years old (interquartile range 3, 16). They also found that approximately 2/3 of patients affected by OM/RPON were female. 4

Signs and Symptoms
OM/RPON typically presents as a headache followed ophthalmoplegia. If headache is present, it is typically unilateral and ipsilateral to the affected eye. The headache may or may not have migrainous features; accompanied by photophobia, phonophobia, or nausea/vomiting. The ophthalmoplegia can occur immediately or up to 14 days after the headache. One or multiple nerves may be affected. The frequency of nerves affected in Gelfand’s paper was CNIII 83%, CNVI 20%, and CNIV 2%. If multiple nerves were affected, CNIII was always included.4 When CNIII is affected it may be a partial or complete palsy. Both ptosis and mydriasis are common, especially among children.

Diagnostic Criteria:
According to the International Classification of Headache Disorder 3-beta1:
A. At least Two attacks fulfilling criterion B.
B. Unilateral headache accompanied by ipsilateral paresis of one, two or all three ocular motor nerves.
C. Orbital, parasellar, or posterior fossa lesion has been excluded by appropriate investigation.
D. Not better accounted for by another ICHD-3 dx
As stated above, before the diagnosis of OM/RPON is made it is very important to rule out other possible etiologies such as aneurysm, schwannoma, granulomatous disease, and inflammatory neuropathy.2

The pathophysiology of OM/RPON is a topic of ongoing debate. The diagnostic criteria in ICHD have been updated over the years to mirror the trends in the etiologic discussion by classifying it first as a migraine, then as a neuralgia, and most recently as a neuropathy.5 In fact, with the newest release of ICHD-3beta, the International Headache Society recommended the term ‘ophthalmoplegic migraine’ be abandoned.1 The driving force for this progression has been the need to explain the reversible contrast enhancement at the root entry zone of the affected cranial nerve.
Some who support the viewpoint of a neuropathy will point to the possibility of a benign neurotropic viral infection and highlight the similarities of the imaging in OM/RPON to those found in Bell’s Palsy.2 Others advocate for an immune-mediated neuropathy similar to chronic inflammatory demyelinating polyneuropathy (CIDP).5 In both of these explanations, the headache of OM/RPON is a result of inflammation of the nerve. The inflammation causes vasoconstriction of the nearby vasculature subsequently triggering the headache. However, these hypotheses are not without their weaknesses, CSF analysis and viral studies typically return unremarkable in OM/RPON.
Even with the current trend towards viewing OM/RPON as a neuropathy, there are still some who continue to advocate for a migrainous etiology. A paper published in 2014 proposed that a migraine induced vasospasm of the arteries supplying CNIII, IV, or VI could lead to ischemia of the nerves causing reversible breakdown of the nerve-blood barrier allowing for contrast extravasation and subsequent nerve enhancement on MRI.3 The authors make a great case, yet still leave questions unanswered. If migraine is the causal process then why does treatment with acute and prophylactic migraine medication offer little to no benefit or protection to patients?
In summary, there is still much work to be done towards reaching an understanding of how and why OM/RPON occurs. It is valuable to consider that OM/RPON may in fact have a multifactorial etiology resulting from processes and predispositions related to both neuropathy and migraine.

Treatment: With such ambiguity clouding the pathophysiology of OM/RPON it follows that there is also uncertainty regarding effective treatment for the condition. Migraine medications both acute and prophylactic have been tried with unconvincing efficacy while the results of steroids have been positive yet mixed. Gelfand found steroids to be beneficial in 54% of cases reviewed. Yet the effects were either unclear, not beneficial or even harmful in 35%, 8%, and 4% respectively.4

Prognosis: Prognosis in OM/RPON is generally excellent and most patients can experience a full recovery in days to weeks. However small minority of patients may be left with
persistent neurological deficits, especially those who suffer from repeated attacks.2,3,4,5

1. The International Classification of Headache Disorders, 3rd edition (beta version).
2. Alexander, et. Al. Ophthalmoplegic Migraine: Reversible Enhancement and Thickening of the Cisternal Segment of the Oculomotor Nerve on Contrast-Enhanced MR Images. AJNR Am J Neuroradiol 19:1887–1891, November 1998
3. Ambrosetto, et. Al. Ophthalmoplegic migraine: From questions to answers. Cephalalgia 2014, Vol. 34(11) 914–919
4. Gelfand, et. Al. Ophthalmoplegic ‘‘Migraine’’ or Recurrent Ophthalmoplegic Cranial Neuropathy: New Cases and a Systematic Review.

Identifier: Moran_CORE_21686

Financial Disclosure: None