Review Article
Cephalalgia
0(0) 1–6
Ophthalmoplegic migraine: ! International Headache Society 2014
Reprints and permissions:
From questions to answers sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0333102414523843
cep.sagepub.com
Paolo Ambrosetto1, Francesca Nicolini2, Matteo Zoli2,
Luigi Cirillo3,4, Paola Feraco5 and Antonella Bacci3
Abstract
Introduction: The International Classification of Headache Disorders classifies ophthalmoplegic migraine (OM) under
‘‘cranial neuralgias and central causes of facial pain.’’
OM is diagnosed when all the following criteria are satisfied:
A. At least two attacks fulfilling criterion B.
B. Migraine-like headache accompanied or followed within
four days of its onset by paresis of one or more of the III, IV and/or VI cranial nerves.
C. Parasellar orbital fissure and posterior fossa lesions ruled out by appropriate investigations.
In children the syndrome is rare and magnetic resonance (MR) shows strongly enhancing thickened nerve at the root
entry zone (REZ).
Method: The authors review the literature focusing on pathogenesis theories.
Results: The authors suggest that ischemic reversible breakdown of the blood-nerve barrier is the most probable cause of
OM and to include MR findings in the hallmarks of the disease.
Conclusion: OM is the same disease in adulthood and childhood, even if in adults the MR imaging findings are negative. In
the authors’ opinion, OM should be classified as migraine.
Keywords
Ophthalmoplegic migraine, neuroradiology, headache, cranial nerve palsy, pediatric
Date received: 7 March 2013; revised: 29 May 2013; 26 July 2013; 29 September 2013; 18 November 2013; 10 January 2014; accepted: 11 January 2014
Introduction
Ophthalmoplegic migraine (OM) is a rare episodic completely. Paralysis has been reported to recover in
childhood condition characterized by recurrent epi- four to 84 days (9), even if in some cases, after multiple
sodes of headache with unilateral ophthalmoplegia episodes, the deficit may be permanent with aberrant
due to paresis or paralysis of the III, IV or VI cranial regeneration of the third nerve (3,10–12). Contrast
nerves (1–4). Most often the disease is reversible and is enhancement MRI shows characteristic reversible
thought to be a self-limited condition (3). OM is recog- focal thickening and enhancement of the cisternal
nized as a cranial neuralgia and not as migraine accord-
ing to the most recent edition of the International 1
Department of Diagnostic Imaging, Villalba Hospital, GVM, Care and
Classification of Headache Disorders (ICHD) (5). In Research, Italy
2
ICHD-I, OM was grouped in the migraine variant Department of Neurosurgery, IRCCS Istituto delle Scienze
Neurologiche, Bologna, Italy
(6). In 2001, the second edition of ICHD (ICHD-II) 3
Department of Neuroradiology, IRCCS Istituto delle Scienze
classified OM in cranial neuralgias on the basis of mag- Neurologiche, Bologna, Italy
netic resonance imaging (MRI) and clinical features (7). 4
Department of Experimental, Diagnostic and Speciality Medicine
In the recently published ICHD third edition beta (DIMES), University of Bologna, Bologna, Italy
5
(ICHD-III-Beta), OM is classified among painful cra- Department of Radiology, Ospedale Santa Chiara, Trento, Italy
nial neuropathies and more specifically as recurrent
Corresponding author:
painful ophthalmoplegic neuropathy (8). Francesca Nicolini, Department of Neurosurgery, IRCCS Istituto delle
The onset of the disease typically occurs in child- Scienze Neurologiche, Via Altura 3, Bologna 40138, Italy.
hood and ocular motor nerve palsy usually recovers Email:
, 2 Cephalalgia 0(0)
tract of the involved nerve, usually the III cranial nerve, knowledge; we found very few cases of positive CT
at the root exit zone (REZ) (6,13,14). (13,21,33). MRI performed during or immediately
Even if in adults the clinical presentation is the same, after the migrainous-like headache attack usually
the MR findings are negative (15). detects enlargement and homogeneous enhancement
Many pathogenetic theories have been suggested, of the III cranial nerve at the REZ even though few
but none of them seem to be conclusive (3,15–18). We cases of OM in children with normal MR have been
briefly discuss the previously reported pathogenesis, reported in the literature (33–35). Enlargement is usu-
and emphasize the theory involving a reversible ische- ally round or trapezoid with the widest area adjacent to
mic breakdown of the blood-nerve barrier. the midbrain, but in some rare cases the enlargement
Finally, we discuss whether OM in children and in and the enhancement of the nerve is linear and spreads
adults is the same disease and whether it should be along the nerve (9,28). Interestingly, in the patient with
classified as migraine or cranial neuralgia. OM and right abducens palsy, reported by Lee et al.
(30), MRI showed only subtle, linear, oblique reversible
enhancement within the right lower pons in an area
Discussion neuroanatomically corresponding to the intra-axial
The ICHD classifies OM under ‘‘cranial neuralgias and roots of the nerve.
central causes of facial pain,’’ and OM is diagnosed Repeat MRI in the quiescent period shows reduction
when all the following criteria are satisfied: or complete resolution of the enhancement, whereas the
thickening of the nerve may last for weeks, months,
years, or it may even be permanent (3). In 1997
A. At least two attacks fulfilling criterion B. Wong and Wong (16) suggested including these MRI
B. Migraine-like headache accompanied or followed findings associated with reversible ophthalmoplegia as
within its onset by paresis of one or more of the supportive diagnostic criteria in OM. As we previously
III, IV and/or VI cranial nerves. emphasized (13), the triad of migraine, III cranial nerve
C. Parasellar orbital fissure and posterior fossa lesions palsy, and enhancement of an enlarged III cranial nerve
ruled out by appropriate investigations. at the REZ during the acute phase, and subtle or no
enhancement during the quiescent phase, should be
When the criteria are satisfied, the diagnosis is def- considered as pathognomonic of probable OM, after
inite OM in patients who have suffered two or more the first attack, and of definite OM after the second
attacks, and probable OM in patients with only a or more attacks; further investigation should be
single attack. Laboratory data including erythrocyte avoided. Because of the self-limiting nature of the dis-
sedimentation rate, rheumatoid factor, lupus erythema- ease, there are few post-mortem studies of patients ful-
tosus (LE), antinuclear antibody, serum venereal dis- filling the general semiology of OM (36,37); none of
ease research laboratory (VDRL) and cerebrospinal them has been conclusive and the pathogenesis of this
fluid (CSF) pressure and analysis are all normal. syndrome remains questionable (36,37). Enhancement
OM in children is a rare condition, characterized by of the cisternal portion of the oculomotor nerve can
recurrent headaches followed by ocular motor nerve occur in a variety of neoplastic and infiltrative condi-
palsy (1–3), with an estimated annual incidence of 0.7 tions (3), benign such as schwannomas, and hemangi-
per million (19). The disease most often occurs in omas, or malignant such as lymphoma, leukemia, and
infancy or childhood, with average age at the onset carcinomatous meningitis (38), but none of these con-
under 10 years (3,20). It has rarely been reported, but ditions could resolve spontaneously.
in such cases patients frequently started their clinical Enhancement of the cisternal portion of the oculo-
history in infancy (9,15,21,22). Children with recurrent motor nerve also occurs in a variety of infectious and
oculomotor paresis without headache have also been noninfectious inflammatory conditions, such as neuro-
reported and diagnosed as having ‘‘ophthalmoplegic borelliosis (28,29,39,40), syphilis (41,42) coccidioidomi-
migraine variant’’ (9,23–27). Usually the III cranial cosis, and human immunodeficiency virus (HIV)
nerve is affected, but involvement of the IV (28) or VI infection (17). In these cases as well, it is highly unlikely
cranial nerves has rarely been reported (29–32); a case that these diseases resolved spontaneously without spe-
of recurrent OM with simultaneous oculomotor and cific treatment.
trochlear nerves palsy with reversible thickening and An arteriovenous malformation (AVM) may have a
enhancement of the trochlear nerve has also been clinical picture mimicking OM (43), but a true AVM
reported (28). In OM the clinical type of migraine unlikely regresses spontaneously and MRI shows evi-
varies from case to case, and may cover the whole dence of flow (3). In a reported case of oculomotor
migraine spectrum (32). Computed tomography (CT) nerve schwannoma at the REZ mimicking OM (44),
is usually reported as negative according to our the paper has too many speculative statements and
Cephalalgia
0(0) 1–6
Ophthalmoplegic migraine: ! International Headache Society 2014
Reprints and permissions:
From questions to answers sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0333102414523843
cep.sagepub.com
Paolo Ambrosetto1, Francesca Nicolini2, Matteo Zoli2,
Luigi Cirillo3,4, Paola Feraco5 and Antonella Bacci3
Abstract
Introduction: The International Classification of Headache Disorders classifies ophthalmoplegic migraine (OM) under
‘‘cranial neuralgias and central causes of facial pain.’’
OM is diagnosed when all the following criteria are satisfied:
A. At least two attacks fulfilling criterion B.
B. Migraine-like headache accompanied or followed within
four days of its onset by paresis of one or more of the III, IV and/or VI cranial nerves.
C. Parasellar orbital fissure and posterior fossa lesions ruled out by appropriate investigations.
In children the syndrome is rare and magnetic resonance (MR) shows strongly enhancing thickened nerve at the root
entry zone (REZ).
Method: The authors review the literature focusing on pathogenesis theories.
Results: The authors suggest that ischemic reversible breakdown of the blood-nerve barrier is the most probable cause of
OM and to include MR findings in the hallmarks of the disease.
Conclusion: OM is the same disease in adulthood and childhood, even if in adults the MR imaging findings are negative. In
the authors’ opinion, OM should be classified as migraine.
Keywords
Ophthalmoplegic migraine, neuroradiology, headache, cranial nerve palsy, pediatric
Date received: 7 March 2013; revised: 29 May 2013; 26 July 2013; 29 September 2013; 18 November 2013; 10 January 2014; accepted: 11 January 2014
Introduction
Ophthalmoplegic migraine (OM) is a rare episodic completely. Paralysis has been reported to recover in
childhood condition characterized by recurrent epi- four to 84 days (9), even if in some cases, after multiple
sodes of headache with unilateral ophthalmoplegia episodes, the deficit may be permanent with aberrant
due to paresis or paralysis of the III, IV or VI cranial regeneration of the third nerve (3,10–12). Contrast
nerves (1–4). Most often the disease is reversible and is enhancement MRI shows characteristic reversible
thought to be a self-limited condition (3). OM is recog- focal thickening and enhancement of the cisternal
nized as a cranial neuralgia and not as migraine accord-
ing to the most recent edition of the International 1
Department of Diagnostic Imaging, Villalba Hospital, GVM, Care and
Classification of Headache Disorders (ICHD) (5). In Research, Italy
2
ICHD-I, OM was grouped in the migraine variant Department of Neurosurgery, IRCCS Istituto delle Scienze
Neurologiche, Bologna, Italy
(6). In 2001, the second edition of ICHD (ICHD-II) 3
Department of Neuroradiology, IRCCS Istituto delle Scienze
classified OM in cranial neuralgias on the basis of mag- Neurologiche, Bologna, Italy
netic resonance imaging (MRI) and clinical features (7). 4
Department of Experimental, Diagnostic and Speciality Medicine
In the recently published ICHD third edition beta (DIMES), University of Bologna, Bologna, Italy
5
(ICHD-III-Beta), OM is classified among painful cra- Department of Radiology, Ospedale Santa Chiara, Trento, Italy
nial neuropathies and more specifically as recurrent
Corresponding author:
painful ophthalmoplegic neuropathy (8). Francesca Nicolini, Department of Neurosurgery, IRCCS Istituto delle
The onset of the disease typically occurs in child- Scienze Neurologiche, Via Altura 3, Bologna 40138, Italy.
hood and ocular motor nerve palsy usually recovers Email:
, 2 Cephalalgia 0(0)
tract of the involved nerve, usually the III cranial nerve, knowledge; we found very few cases of positive CT
at the root exit zone (REZ) (6,13,14). (13,21,33). MRI performed during or immediately
Even if in adults the clinical presentation is the same, after the migrainous-like headache attack usually
the MR findings are negative (15). detects enlargement and homogeneous enhancement
Many pathogenetic theories have been suggested, of the III cranial nerve at the REZ even though few
but none of them seem to be conclusive (3,15–18). We cases of OM in children with normal MR have been
briefly discuss the previously reported pathogenesis, reported in the literature (33–35). Enlargement is usu-
and emphasize the theory involving a reversible ische- ally round or trapezoid with the widest area adjacent to
mic breakdown of the blood-nerve barrier. the midbrain, but in some rare cases the enlargement
Finally, we discuss whether OM in children and in and the enhancement of the nerve is linear and spreads
adults is the same disease and whether it should be along the nerve (9,28). Interestingly, in the patient with
classified as migraine or cranial neuralgia. OM and right abducens palsy, reported by Lee et al.
(30), MRI showed only subtle, linear, oblique reversible
enhancement within the right lower pons in an area
Discussion neuroanatomically corresponding to the intra-axial
The ICHD classifies OM under ‘‘cranial neuralgias and roots of the nerve.
central causes of facial pain,’’ and OM is diagnosed Repeat MRI in the quiescent period shows reduction
when all the following criteria are satisfied: or complete resolution of the enhancement, whereas the
thickening of the nerve may last for weeks, months,
years, or it may even be permanent (3). In 1997
A. At least two attacks fulfilling criterion B. Wong and Wong (16) suggested including these MRI
B. Migraine-like headache accompanied or followed findings associated with reversible ophthalmoplegia as
within its onset by paresis of one or more of the supportive diagnostic criteria in OM. As we previously
III, IV and/or VI cranial nerves. emphasized (13), the triad of migraine, III cranial nerve
C. Parasellar orbital fissure and posterior fossa lesions palsy, and enhancement of an enlarged III cranial nerve
ruled out by appropriate investigations. at the REZ during the acute phase, and subtle or no
enhancement during the quiescent phase, should be
When the criteria are satisfied, the diagnosis is def- considered as pathognomonic of probable OM, after
inite OM in patients who have suffered two or more the first attack, and of definite OM after the second
attacks, and probable OM in patients with only a or more attacks; further investigation should be
single attack. Laboratory data including erythrocyte avoided. Because of the self-limiting nature of the dis-
sedimentation rate, rheumatoid factor, lupus erythema- ease, there are few post-mortem studies of patients ful-
tosus (LE), antinuclear antibody, serum venereal dis- filling the general semiology of OM (36,37); none of
ease research laboratory (VDRL) and cerebrospinal them has been conclusive and the pathogenesis of this
fluid (CSF) pressure and analysis are all normal. syndrome remains questionable (36,37). Enhancement
OM in children is a rare condition, characterized by of the cisternal portion of the oculomotor nerve can
recurrent headaches followed by ocular motor nerve occur in a variety of neoplastic and infiltrative condi-
palsy (1–3), with an estimated annual incidence of 0.7 tions (3), benign such as schwannomas, and hemangi-
per million (19). The disease most often occurs in omas, or malignant such as lymphoma, leukemia, and
infancy or childhood, with average age at the onset carcinomatous meningitis (38), but none of these con-
under 10 years (3,20). It has rarely been reported, but ditions could resolve spontaneously.
in such cases patients frequently started their clinical Enhancement of the cisternal portion of the oculo-
history in infancy (9,15,21,22). Children with recurrent motor nerve also occurs in a variety of infectious and
oculomotor paresis without headache have also been noninfectious inflammatory conditions, such as neuro-
reported and diagnosed as having ‘‘ophthalmoplegic borelliosis (28,29,39,40), syphilis (41,42) coccidioidomi-
migraine variant’’ (9,23–27). Usually the III cranial cosis, and human immunodeficiency virus (HIV)
nerve is affected, but involvement of the IV (28) or VI infection (17). In these cases as well, it is highly unlikely
cranial nerves has rarely been reported (29–32); a case that these diseases resolved spontaneously without spe-
of recurrent OM with simultaneous oculomotor and cific treatment.
trochlear nerves palsy with reversible thickening and An arteriovenous malformation (AVM) may have a
enhancement of the trochlear nerve has also been clinical picture mimicking OM (43), but a true AVM
reported (28). In OM the clinical type of migraine unlikely regresses spontaneously and MRI shows evi-
varies from case to case, and may cover the whole dence of flow (3). In a reported case of oculomotor
migraine spectrum (32). Computed tomography (CT) nerve schwannoma at the REZ mimicking OM (44),
is usually reported as negative according to our the paper has too many speculative statements and
