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Paediatric Tolosa-Hunt syndrome: the need for treatment guidelinesand renewed criteria

Karolina Pienczk-Reclawowicz, Ewa Pilarska,

Malgorzata Lemka, Seweryna KoniecznaDepartment of Developmental Neurology, Medical University of Gdansk, Gdansk,

Poland.

Correspondence to: pienczk@gumed.edu.pl

doi: 10.1111/j.1469-8749.2010.03687.x

SIR–Tolosa-Hunt syndrome (THS) is a rare disorder, espe-cially in the paediatric population, characterized by unilateralpainful ophthalmoplegia of, typically, a relapsing-remittingcourse and a substantial response to corticosteroids. Thesymptoms of THS are not specific and clinical criteria them-selves do not guarantee a firm diagnosis. Neuroimaging or

biopsy confirming granulomatous inflammation is essential toa diagnosis of THS.

 Although diagnostic criteria were established by the Inter-national Headache Society in 1988, then revised in 2004(Table I),1  THS remains a diagnosis of exclusion of other causes of painful ophthalmoplegia, (e.g. neoplasms,aneurysms, cranial neuropathy [diabetes mellitus], opthalmo-plegic migraine, intracranial vasculitis, pseudotumor of theorbit, basal meningitis, or cavernous sinus thrombosis).2

Scarcity of data on paediatric THS means that steroid dosesas well as the duration of steroid therapy are not clearly speci-fied. In the patient we report, lack of precise therapeutic

guidelines resulted in prolonged steroid administration andsubsequent severe side effects of the treatment.

 A 14-year-old female with no previous history of recurrent headaches or any chronic disorder was admitted to the Devel-opmental Neurology Department of the Medical University of Gdansk with left-sided frontal headache and retro-orbitalpain of subacute onset that was present for about a monthbefore admission. The symptoms were not preceded by injury,fever, or infection. The symptoms were constant (present alsoat night), of mild intensity, and unresponsive to intermittent 

analgesics. As time went by, diplopia appeared and the pain

became more intense.On admission, neurological examination revealed paresis of 

the left VI cranial nerve. The laboratory tests (e.g. blood mor-phology, C-reactive protein, erythrocyte sedimentation rate,coagulation studies) were normal. Magnetic resonance imag-ing (MRI) with magnetic resonance angiography (MRA) didnot show any abnormalities. Steroid therapy was started withlow doses of dexamethasone (about 0.2mg  ⁄  kg  ⁄  day). The paindiminished within 24 hours and disappeared completely after3 days. However, it was only after almost a week that diplopiadisappeared. The steroids were gradually reduced and totally 

 withdrawn within 2 weeks. After 24 hours of steroid discon-tinuation the female reported recurrence of severe pain in the

same location. Exophthalmos and paresis of the left IV and VIcranial nerves were observed. Repeat MRI and MRA showednarrowing of the carotid artery within the cavernous sinus andpost-gadolin enhancement of fatty tissue within the left orbit (Fig. 1a,b), most probably of inflammatory origin. Steroidtherapy was restarted (again about 0.2mg  ⁄  kg  ⁄  day). Painresolved within 24 hours, other symptoms within 5 days. Thepatient was discharged with the recommendation of gradual,slow reduction of dexamethasone. After 4 days she was admit-ted again owing to severe pain in the same location. Exo-phthalmos and slight paresis of the left III and VI cranialnerves, which resulted in mild diplopia with anizocoria (L>R),

 were noted (Fig. 1c,d). Repeat MRI and MRA showed no pro-gression. Repeat laboratory tests were normal. Increase of dexamethasone to 6mg (0.1mg  ⁄  kg  ⁄  day) was enough to resolvethe pain (24 h) and neurological symptoms (2 d).

 The female was seen in the outpatient department onseveral occasions during which recurrences of the painful oph-thalmoplegia were reported but the symptoms were muchmilder. Total reduction of treatment was not possible before4 months. Prolonged steroid therapy resulted in significant 

 weight gain, acne, and numerous striae of the skin. The femalebecame withdrawn and then depressed, requiring psycho-therapy.

Four months after steroid discontinuation, the femaleremained asymptomatic with total regression of MRI changes.

 The most recent case report of paediatric THS by Zanuset al.3 describes an 8-year-old female in whom dexamethasonein a dose of 0.2mg  ⁄  kg  ⁄  day required only 8 days of administra-tion. In our patient the same dosage was used but it seems it 

 was too low to overcome the inflammation in a short time. Yeung et al. described a 9-year-old male for whom dexameth-asone in a dose of 1mg  ⁄  kg  ⁄  day selectively reduced orbitalpain, but only high-dose prednisolone therapy (2mg  ⁄  kg  ⁄  day),resulted in complete resolution of all THS symptoms.4 Inboth aforementioned cases it took much longer than 72 hours

Table I: Current diagnostic criteria for Tolosa-Hunt syndrome redefined in

2004 by the International Headache Society1

1. One or more episodes of unilateral orbital pain, persisting for weeks

if untreated.

2. Paresis of one or more of the third, fourth, and  ⁄  or sixth cranial

nerves and  ⁄  or demonstration of granuloma by magnetic resonance

imaging or biopsy.

3. Paresis coincides with the onset of pain or follows it within 2 wks.

4. Pain and paresis resolve within 72 h when treated adequately with

orticosteroids.

5. Other causes excluded by appropriate investigations.

ª The Authors. Journal compilation ª Mac Keith Press 2010 873

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for cranial nerves paresis to recede. Adult cases of THSdescribed by Cakirer demonstrated resolution of the cranialnerves paralysis within 2 to 8 weeks.5  This tendency has beenreported in many other cases of adult-onset THS.

 The need for the revision of the fourth diagnostic criterionfor THS was proposed for the first time in 2008 by Colnaghiet al.6 (according to them in this criterion only pain resolutionshould be limited to 72 hours), but their observations concernchiefly adult populations with THS. They claim that high-dose steroids are more likely than lower doses to be effectivein THS patients (regarding both resolution of symptoms andavoidance of recurrences) and emphasize the importance of repeat neuroimaging, which helps to avoid diagnostic pitfalls.Obviously this is all of paramount importance as parasellartumours, for example, may be responsive to steroids andimprove after such therapy.7

 The fourth criterion includes the feature of resolving thesymptoms within 72 hours of adequate steroid therapy, but 

does not define what ‘adequate steroid therapy’ means ineveryday practice.

O’Connor and Hutchinson report a case of a female with THS who was reluctant to take steroids but who had a dra-matic response to infliximab.8 Clinical trials are needed toconfirm if this could be an alternative treatment for paediatric

 THS patients.On the basis of our observations and review of the literature

 we suggest that (1) there is a need for the fourth THS diagnos-tic criterion revision, (2) in subacute forms of THS initial neu-roimaging can be normal, and (3) establishing an algorithm of therapeutic management in paediatric patients with THS is of essential importance (the kind and dosage of steroids, theduration of therapy, alternative drugs in cases of steroids un-responsiveness, or serious side effects). To our knowledge thisissue has also never been resolved in adult patients with THS.

REFERENCES

1. Headache Classification Committee of the International

Headache Society. The International Classification of Head-

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2. Curone M, Tullo V, Proietti-Cecchini A, Peccarisi C, Leone

 M, Bussone G. Painful ophthalmoplegia: a retrospective

study of 23 cases. Neurol Sci 2009; 30(Suppl.1): 133–5.

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5. Cakirer S. MRI findings in Tolosa-Hunt syndrome before

and after systemic corticosteroid therapy. Eur J Radiol 2003;

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6. Colnaghi S, Versino M, Marchioni E. ICHD-II diagnostic

criteria for Tolosa-Hunt syndrome in idiopathic inflamma-

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Cephalalgia 2008; 28: 577–84.

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a b c

d

Figure 1: (a,b) Magnetic resonance imaging findings after first recurrence of painful ophthalmoplegia. (a) Hyperintensity of fatty tissue within the medial part

of the left orbit suggesting inflammatory process. (b) Note narrowing of the left carotid artery within the left cavernous sinus. (c,d) Residual symptoms of the

left oculomotor and abducens nerve palsy with mild left-sided exophthalmos 24h after the second admission and increase of dexamethasone. (c) Note slight

left pupil dilation. Abducens nerve palsy appears as asymmetry of corneal light reflexes and diplopia.

874 Developmental Medicine & Child Neurology  2010, 52: 873–874