|Year : 2014 | Volume
| Issue : 1 | Page : 47-50
Vivek Guleria, Daya Jha, Salil Gupta, Velu Nair
Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Web Publication||15-Mar-2014|
Medical Specialist, MH Palampur, Himachal Pradesh - 176 061
Source of Support: None, Conflict of Interest: None
Painful ophthalmoplegia refers to a multiple cranial nerve syndrome involving oculomotor, trochlear, abducens, and ophthalmic division of the trigeminal nerve. Among various etiologies of painful ophthalmoplegias, Tolosa-Hunt syndrome, a relatively benign condition, used to be a diagnosis of exclusion. With advent of newer imaging techniques, it can now be considered as primary differential in painful ophthalmoplegias and patient can benefit with early introduction of steroids. We describe herein a patient with painful ophthalmoplegia in which early diagnosis was made, based on clinical and magnetic resonance imaging (MRI) findings.
Keywords: Cranial nerve palsy, painful ophthalmoplegia, Tolosa-Hunt Syndrome
|How to cite this article:|
Guleria V, Jha D, Gupta S, Nair V. Painful ophthalmoplegia. Indian J Pain 2014;28:47-50
| Introduction|| |
Painful ophthalmoplegia refers to a multiple cranial nerve syndrome involving oculomotor, trochlear, abducens, and ophthalmic division of the trigeminal nerve. Various etiologies have been reported; these include infections, inflammations, sphenoid sinus mucocele, tumors, dural arteriovenous malformation, trauma, and diabetes mellitus.
Tolosa-Hunt syndrome (THS), a steroid-responsive painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus or orbital apex was first described by Tolosa in 1954.  Over the years various diagnostic criteria have evolved, helping in early diagnosis of THS.
| Case Report|| |
We present the case of a 29-year-old previously healthy female who was admitted at our center with 3 days history of severe right-sided, non-throbbing headache which was continuous. There was no history of similar complains in the past. Since last 24 h she had developed drooping of right eyelid and double vision while looking towards left side. Headache had persisted in spite of taking nonsteroidal anti-inflammatory drugs (NSAIDs).
On examination she had a weight of 69 kg; body mass index (BMI) 36 kg/m 2 ; blood pressure (BP) 126/70 mmHg; pulse 88/min; 6/6 vision bilaterally; complete right palpebral ptosis [Figure 1]; exotropia of the primary look of the right eye; paresis of the third, fourth, and sixth right cranial nerves [Figure 1]; right pupil dilated; and not reacting to direct and indirect light with normal left pupil reacting to both direct and indirect light. Fundus examination was normal. Left eye and the rest of the physical examination did not show any abnormalities.
|Figure 1: Ptosis of right eye with right medial rectus palsy on admission. Complete recovery within 24 h of steroids|
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Her laboratory tests showed hemoglobin of 12 g/dl, white blood cell count 7, 600/dl, platelets 3.1 lakh/dl, glucose 98 mg/dl, urea 28 mg/dl, creatinine 0.6 mg/dl, serum bilirubin 0.8 mg/dl, aspartate aminotransferase (AST) 23 IU/L, alanine aminotransferase (ALT) 34 IU/L, C-reactive protein (CRP) negative, erythrocyte sedimentation rate (ESR) 18 mm 1 st h, enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative; and hepatitis B surface antigen (HBsAg) negative.
Chest X-ray was normal. Thyroid function tests showed; total triiodothyronine (T3) 0.53 ng/ml (normal 0.60-1.81), thyroxin (T4) of 5.70 mg/dl (5.01-12.45), and thyroid-stimulating hormone (TSH) of 0.93 mIU/ml (0.35-5.50). Cerebral spinal fluid showed 3 mononuclear cell/μl; glucose 60 mg/dl (blood glucose 146 mg/dl); proteins 24 mg/dl; and staining,Adenosine deaminase ADA, and cultures were negative. Antinuclear antibody (ANA) was negative, cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and perinuclear ANCA (p-ANCA) negative. Magnetic resonance imaging (MRI) showed 1.7 × 1.7 cm size (T1 and T2) isodense soft tissue in region of right orbital apex and cavernous sinus region with post-contrast enhancement [Figure 2]. Based upon the findings a diagnosis of THS was made and patient was started oral prednisolone 1 mg/kg. She showed a dramatic response to steroids within 24 h as shown in [Figure 1]. Steroids were gradually tapered over 2 months.
|Figure 2: A 1.7 × 0.7 cm size T1 and T2 isointense soft tissue mass in the region of right side of orbital apex and cavernous sinus which shows post contrast enhancement|
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| Discussion|| |
Painful ophthalmoplegia caused by inflammatory conditions in the region of the superior orbital fissure has been recognized for over a century. In addition to inflammmatory conditions, there are various other etiologies as well.
Causes of painful ophthalmoplegia
Skull base fracture
Carotid artery aneurysm
Intracavernous internal carotid artery aneurysm
Cavernous sinus thrombosis
Primary tumors meningioma
Systemic lupus erythematosus
Giant cell arteritis
Among all the etiologies of painful ophthalmoplegias, THS is a relatively benign disease. Tolosa  in 1954 reported a patient with left orbital pain, ipsilateral visual loss, and total left ophthalmoplegia. Patient died 3 days after exploratory craniotomy. At postmortem, he found a nonspecific granulomatous lesion, compressing carotid artery and nerve trunks in lateral wall of cavernous sinus.
In 1961, Hunt et al.,  described six patients with similar complaints and proposed that this syndrome of painful ophthalmoplegia was caused by inflammation in cavernous sinus. They postulated the following diagnostic criteria:
- Pain may precede the ophthalmoplegia by several days, or may not appear until sometime later. It is a steady pain behind the eye that is often described as "gnawing" or "boring".
- Neurological involvement is not confined to the third cranial nerve, but may include the fourth, sixth, and first division of the fifth cranial nerves.
- Symptoms last for days to weeks.
- Spontaneous remissions occur, sometimes with residual neurological deficit.
- Attacks recur.
- Studies, including angiography, surgical exploration, produce no evidence of involvement of structures outside of the cavernous sinus.
In 1966 Smith and Taxdal  coined the word "Tolosa-Hunt syndrome". They reported dramatic response of steroids in these patients. In 1988, the International Headache Society (IHS) defined the diagnostic criteria  of THS. Till this time THS was a diagnosis of exclusion, but with advent of newer imaging techniques, various studies came up which laid the importance of neuroimaging in diagnosis of THS. Pascual et al.,  in 1999, did MRI in 22 patients meeting the IHS criteria (1988) for THS. MRI revealed a convex enlargement of the cavernous sinus by an abnormal tissue isointense with gray matter on short repetition time/echo time (TR/TE) images and isohypointense on long TR/TE images in all these patients showing contrast enhancement.
So in 2004, IHS redefined the diagnostic criteria of THS specifying that granuloma, demonstrated by MRI or biopsy is required for diagnosis. The International Headache Classification (ICHD-2) described THS as:
- One or more episodes of unilateral orbital pain persisting for weeks if untreated
- Paresis of one or more of the third, fourth, and/or sixth cranial nerves and/or demonstration of granuloma by MRI or biopsy
- Paresis coincides with the onset of pain or follows it within 2 weeks
- Pain and paresis resolve within 72 h when treated adequately with corticosteroids
- Other causes have been excluded by appropriate investigations. Other causes of painful ophthalmoplegia include tumors, vasculitis, basal meningitis, sarcoid, diabetes mellitus and ophthalmoplegic "migraine".
Various studies have also documented abnormal findings in the region of the cavernous sinus, superior orbital fissure ,, which regress after steroids.
MRI has considerably simplified the differential diagnosis, but it has not completely resolved it. Alterations of shape and signal of the cavernous sinus are similar to those of lymphoma, sarcoidosis, and meningioma. When MRI is normal; diabetic ophthalmoplegia, migrainous ophthalmoplegia, and giant-cell arteritis must also be considered. High resolution computed tomography (CT) can also demonstrate soft tissue changes in the region of the cavernous sinus/superior orbital fissure, but is less sensitive than MRI. , Thus, even if CT is normal, MRI must still be performed to appropriately evaluate the region of the cavernous sinus or superior orbital fissure.
In literature, treatment with steroids at a dose of 1 mg/kg/day tapered slowly over 3-4 months has been well-documented.  With the institution of corticosteroid therapy, the natural course is altered with marked improvement within 48 h. Foubert-Samier et al.,  have successfully treated steroid-resistant THS with focal radiotherapy to cavernous sinus. Infliximab has also been used successfully to treat steroid resistant THS. 
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[Figure 1], [Figure 2]