Abstract
Introduction
The Tolosa–Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by non-specific granulomatous inflammation in the cavernous sinus. In most cases, clinical manifestations respond dramatically to corticosteroid therapy (1). We report on a patient with THS who progressively became intolerant to steroids and was treated with radiotherapy.
Case report
A 32-year-old woman without any significant previous medical history developed an intense left temporo-orbital pain with horizontal diplopia, left adbucens nerve palsy and hypoaesthesia in the territory of the first branch of the left trigeminal nerve. The headaches were throbbing and constant all day long. Nausea and vomiting were sometimes present. A first workout was normal including laboratory testing (haematology, erythrocyte sedimentation rate, serum chemistry, Borrelia burgdorferi serology, anti-DNA antibodies and cerebrospinal fluid), brain magnetic resonance imaging (MRI), orbital computed tomography (CT), and chest x-rays. Prednisolone was started on 17 November with 32 mg/day. The pain disappeared after 3 days. The ophthalmoparesis and the hypoaesthesia resolved soon after. Prednisolone was completely stopped on 20 December. The orbital pain and the left sixth nerve palsy relapsed 8 days later. Steroids were restarted with clinical improvement within a few days. By the end of January, while still on 16 mg/day of Prednisolone, the headaches increased and a left third nerve palsy appeared. An intra-arterial angiogram of carotid arteries was normal. The orbital venography revealed a reduced perfusion of the left cavernous sinus. A second brain MRI revealed an enlargement of the left cavernous sinus with contrast enhancement (Fig. 1). Prednisolone was increased up to 64 mg/day. The pain disappeared in 24 h and the ophthalmoplegia regressed nearly completely within a few days. In April, she stopped taking Prednisolone on her own initiative and suffered a new relapse of her symptoms a few days later. Despite various systemic side-effects, Prednisolone was again started at 64 mg/day associated with 50 mg of Azathioprine. This time, the pain was not completely relieved. The steroids were slowly decreased. In July, while still on 4 mg/day of Prednisolone, the patient suffered a new relapse with intense left orbital headaches, left sixth nerve palsy, hypoaesthesia in the region of the three branches of the left trigeminal nerve and left masticator muscles paresis. A left carotid angiography was once again normal. Brain MRI revealed an abnormal mass lesion enlarging the left cavernous sinus, isointense to grey matter on T1- and hypointense on T2-weighted images with marked enhancement after i.v. gadolinium injection. The mass extended to the left foramen ovale, the left Gasserian ganglion, the tentorial notch, and the ipsilateral orbital apex (Fig. 2). Analgesics, 24 mg of Prednisolone, and 150 mg of Azathioprine a day, failed to relieve the symptoms.
Coronal section of brain magnetic resonance imaging (MRI), T1-weighted before (A) and after (B) gadolinium administration. Enlargement of the left cavernous sinus with contrast enhancement.
Coronal section, T1-weighted before (A) and after (B) gadolinium administration, axial section T1-weighted after gadolinium (C) and coronal section, T2-weighted of brain magnetic resonance imaging (MRI) (D). Abnormal mass lesion enlarging the left cavernous sinus, extending to the left foramen ovale, and the left Gasserian ganglion, with strong contrast enhancement.
The unacceptable aesthetic side-effects of the prolonged exposure to steroids and above all the occurrence of a myopathy with disabling proximal weakness of the lower limbs led us to choose this unusual low dose of Prednisolone. Radiotherapy was started on 8 August with 10 MeV photons and a total dose of 30 Gy over a period of 22 days. The headaches as well as the palsy of the fifth and sixth nerves improved after 15 days. In September, brain MRI revealed a marked reduction of the abnormal mass lesion. In November, corticoids and Azathioprine were stopped. The patient still complained of a slight hypoaesthesia of the left hemiface. During the following months, she only suffered from tension-type headaches and the neurological examination became normal. The ophthalmoplegia did not relapse. The visual acuity and visual evoked potentials remained normal. The last MRI, performed more than 3 years later, was normal (Fig. 3).
Coronal section, T1-weighted of brain magnetic resonance imaging (MRI) showing normal left cavernous sinus.
Discussion
Our patient met the International Headache Society (IHS) criteria for THS (2): (i) episodes of unilateral orbital pain; (ii) association with paralysis of one or more of the third, fourth and sixth cranial nerves; (iii) pain relief within 72 h after initiation of corticosteroids; and (iv) exclusion of other causative lesions by neuroimaging and carotid angiography. The complete workout showed no evidence for another aetiology. The characteristics of the abnormal mass lesion located in the left cavernous sinus were consistent with previous reports of MRI findings in THS (3, 4). Differential diagnosis includes other granulomatous diseases (sarcoidosis, Wegener vasculitis), meningioma, lymphoma and perineural neoplasic infiltration, but these diagnoses could be reasonably excluded because (i) there were no systemic symptoms and no other evidence of systemic disease even nearly 1 year after the onset; (ii) meningiomas rarely respond to steroid therapy and are usually not painful; and (iii) there was no extension of neoplasic tissue. The long course and the progressive intolerance to steroids justified a more aggressive therapy.
Considering the documented response of orbital pseudotumour to radiotherapy (5, 6) and the similarities between this affliction and THS, a beneficial effect was expected. Actually, we found an early objective clinical improvement, with normalization of the ocular movements and an important reduction of headaches. Follow-up MRI revealed a progressive disappearance of the granulomatous mass. There were no side-effects and particularly no radiation-induced damage to the optic nerves. More than 3 years later the patient remained asymptomatic. Radiotherapy also allowed a prompt and complete withdrawal of steroids and Azathioprine.
To our knowledge, there are only two previous reports of radiotherapy for THS. Nasr et al. (7) reported the case of a woman with THS permanently dependent on prednisone treatment. After 10 months of evolution, she was irradiated with 50 Gy. Two years later, she was free of pain with a minimal limitation of vertical movements of the right eye and a slight hypoaesthesia in the region of the maxillary nerve. Luchin et al. (8) also reported a case of THS with gradual resistance to steroid therapy and a high-density zone in the affected cavernous sinus on CT scan. The patient was treated with proton irradiation at a dose of 60 Gy. Four years of clinical remission were observed. The CT scan became normal. Other details are lacking. Our case is the third reported THS successfully treated with radiotherapy and, among these, the first with diagnosis and follow up supported by brain MRI. Thus, radiotherapy may be a safe and effective treatment for THS when the usual medical treatment is contra-indicated, not tolerated, or ineffective.