As we stand today at the doorstep to a new classification of headache disorders by the International Headache Society (IHS), debates continue for the nosological entity and diagnostic criteria of several headache disorders, prominent among which is ophthalmoplegic migraine (OM). We feel that future classification systems need to be simple, pragmatic, unambiguous and easy to be used by clinicians both for research purpose and routine patient assessment and care. It is in the backdrop of this that new classification, nomenclature and diagnostic criteria for OM (an uncommon entity known for over 150 years) need to be discussed.
The currently prevailing International Classification of Headache Disorders 2004 (ICHD-2),[1
] classifies OM not as a subtype of migraine but as a cranial neuralgia. This probably had been made in view of a suggestion by Daroff[2
] in an editorial published in connection with a publication by Lance and Zagami[3
] in 2001, describing a single patient (one out of five cases) where thickening and contrast enhancement could be seen at the exit zone of the third cranial nerve on contrast-enhanced magnetic resonance (MR) imaging and another who developed ophthalmoplegia with headache following an injection of triple vaccine. This was interpreted as an inflammatory demyelinating neuropathy and the migraine–like headache being generated through activation of the trigemino-vascular pathway stimulated by noxious stimuli carried by proprioceptive fibers of the ophthalmic division from the trunk of the third cranial nerve. Of course, there had been at least 11 similar reports (describing 18 patients) prior to Lance and Zagami's[3
However, only 1 year later, Carlow[4
] reported similar findings in six children with OM and offered an excellent hypothesis encompassing the then-known migraine pathophysiology that would be convincing enough to consider OM a migraine variant. Thus, where do we stand? The concept of OM remains debatable even today as we have no histologic/immunologic evidence about the exact pathology. However, ICHD is primarily a clinical classification system based on clinical characteristics and radiological findings. And, to call a headache disorder “secondary” or nonprimary may be problematic when the cause–effect relationship is not clear and purely hypothetical.
] made an excellent summary of all cases of OM reported between 1993 (that is after availability of MR imaging) and 2007 (including three patients of their own) and pleaded for a new classification system and diagnostic criteria. Lane and Davies[6
] described only two patients of OM but with diverse clinical details pointing out the heterogeneous nature of OM and also pleaded for an all-encompassing new classification. In an editorial following this and another report, Friedman[7
] has proposed a new classification of OM in 2009. However, this new system is also not unambiguous and, although the editorial mentions of a large series of OM patients (mostly adults) from India by Lal et al
] an essential feature highlighted in this study, is not reflected in the proposed classification. And, this is the difference in clinical and radiological features between childhood-onset and adult-onset patients with OM. We are also not at ease with introduction of the term “probable” in a condition with a positive clinical sign where use of such adjectives would only increase the preexisting confusion rather than clarifying it.
In this communication, we would first present our own observations on OM seen over 5 years and would then proceed to describe a more simple classification and diagnostic criteria for this vexing disorder.
Summary of case studies of OM: Our experience (2005–2010)
Between June 2005 and May 2010, we encountered 18 new cases of OM in our general neurology clinic, which mostly caters to adult patients. All cases fulfilled the ICHD2 diagnostic criteria of OM except that all had single attacks initially (but had past history of having had several attacks of migraine without aura [MAO]). The total number of headache patients seen during this period would be approximately 4000, yielding an approximate clinic incidence of OM to be 0.45%. The age of the subjects at presentation varied from 27 to 51 years (mean – 37 years) and there were 13 female and five male patients. No patient had past history of ophthalmoplegia, but all suffered from MAO in the past for 6–14 years. However, none ever had been on any migraine prophylaxis on a regular basis. None reported any systemic symptoms. Diabetic painful carnial neuropathy, ophthalmoplegia from tubercular basal meningitis, Tolosa-Hunt syndrome, orbital myositis, sarocoidosis, unruptured infraclinoid aneurysm of internal carotid artery and parasellar tumors were carefully excluded by detailed clinical examination and appropriate investigations like hematology, routine blood biochemistry, cerebrospinal fluid (CSF) studies in some, contrast MR imaging of brain and orbits and MR angiography.
All 18 cases underwent detailed hematological (including coagulation profile), biochemical (including lipid profile and glucose tolerance test) and vasculitis screening tests (ESR, C-reactive protein, rheumatoid factor, ANA, DS-DNA, P-ANCA and C-ANCA) and chest radiographs. All these yielded normal results. All underwent contrast-enhanced MR scan of brain and orbit using 3 mm slices with a 1.5T scanner and the region of the basal cisterns and cavernous sinuses were carefully examined. All yielded normal results. MR angiographies were performed in the same sitting and were normal in all cases. CSF studies were performed in seven cases, and yielded normal results.
Pain was ipsilateral to the ophthalmoplegia in all, involving the orbit, periorbital, frontal and temporal regions. In eight patients, pain spread to the occipital region but none reported holocranial pain. Pain was pulsatile (like their previous migraine headaches) in most (12 cases) and aching/boring in nature in six. It was variable during the day from moderate to severe and, in all cases, was associated with nausea and photo and/or phonophobia but with vomiting in a minority (three cases). None reported any increase in frequency or severity in their migraine attacks preceding the pain onset that led to ophthalmoparesis.
Time from onset of pain to ophthalmoplegia varied from 4 to 7 days (mean 5.5 days). Pain persisted all along till presentation to clinic (2–6 days) and continued till institution of therapy. In no case did pain subside with onset of ophthalmoplegia.
Of the 18 cases, 14 had sixth nerve palsies and the remaining four had palsies of the third cranial nerve. No case had more than one ocular motor nerve involvement. None had any sensory loss in the distribution of the ophthalmic division of trigeminal nerve. Detailed clinical examination did not reveal any other abnormal neurological signs.
Based on our previous experience with a few similar cases, after full investigations, all cases were started on prednisolone 40–60 mg/day and continued for 5 days, after which the dosage of corticosteroids was gradually reduced and finally stopped in 2 weeks.
Pain subsided in all in 4–7 (mean 5.8) days time after institution of therapy, but ophthalmoparesis took 9–16 (mean 11) days to recover fully in all cases as assessed by disappearance of diplopia and return of full ocular movements. Orbital myositis, which is also steroid responsive, had been earlier excluded by contrast-enhanced MR imaging of brain and orbits.
All cases were followed-up for at least 6 months. In two patients, symptoms recurred within 4 and 7 weeks of withdrawal of corticosteroids. One developed pain with recurrence of ophthalmoplegia and one developed similar pain only but with vomiting. Both were restarted on steroids. Both became asymptomatic in 7–10 days time. Both had repeat neuroimaging (with contrast), which yielded normal results. These two cases apart, five more cases developed mild to moderate ipsilateral pulsatile headaches after about 3 months of therapy withdrawal and were started on Flunarazine (a Ca-channel blocker) to which they responded.