Makindo Medical Notes

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About Tolosa-Hunt Syndrome

• Tolosa-Hunt Syndrome (THS) is a rare condition causing painful ophthalmoplegia due to nonspecific granulomatous inflammation of the cavernous sinus or superior orbital fissure.
• Typically presents with severe unilateral periorbital headache and ophthalmic cranial nerve palsies (III, IV, VI, ± V1).
• It is steroid-responsive, with pain usually improving within 24–72 hours of corticosteroid therapy.

Aetiology

The exact cause is unknown. THS is largely idiopathic, but involves granulomatous inflammation in the cavernous sinus/superior orbital fissure.

• Idiopathic Inflammation: Most common presentation, no underlying cause identified.
• Granulomatous Infiltration: Affects cranial nerves III, IV, VI and V1, occasionally extending to the optic nerve (causing visual loss).
• Secondary Causes: Rarely linked to infections, malignancy, or systemic inflammatory disease (e.g., sarcoidosis, vasculitis).

Clinical Presentation

• Unilateral orbital/temporal pain: sharp or stabbing, severe.
• Ophthalmoplegia: restriction of eye movement with diplopia, ptosis, and external ophthalmoplegia.
• V1 Trigeminal Involvement: forehead sensory changes/paraesthesia.
• Photophobia: often reported.
• Rarely: encephalopathy or visual loss if inflammation extends.

International Headache Society Criteria (ICHD-3)

• Unilateral orbital pain lasting up to 8 weeks if untreated.
• Paresis of III, IV, or VI cranial nerves (± V1 involvement).
• Pain improves within 72 hours of starting corticosteroids.
• Other causes excluded by neuroimaging (tumour, aneurysm, infection).

Differential Diagnoses

• Cavernous sinus thrombosis: often infectious, systemic sepsis signs.
• Metastatic deposits: carcinoma/lymphoma affecting cavernous sinus.
• Carotid aneurysm/dissection: vascular cause of painful ophthalmoplegia.
• Acute angle-closure glaucoma: painful red eye, raised intraocular pressure.
• Headache disorders: migraine/cluster headache but without persistent nerve palsy.
• Multiple sclerosis: demyelinating cranial neuropathies.
• Infectious causes: herpes zoster ophthalmicus, syphilis, fungal sinus disease.

Investigations

• Blood Tests: FBC, U&E, LFTs, CRP, ESR, ANA, ANCA (to exclude systemic inflammation).
• Neuroimaging:
  • MRI brain ± contrast: may show cavernous sinus enhancement/enlargement, or be normal.
  • CT/MR angiography: if aneurysm or dissection suspected.
• CSF analysis: May show nonspecific inflammation; helps exclude infection/neoplastic infiltration.
• Other: Anti-GQ1b antibodies if Miller-Fisher overlap considered (rare).

Management

Corticosteroids are the cornerstone of therapy. Pain usually improves dramatically within 2–3 days.

• Corticosteroids: high-dose oral or IV steroids (e.g. prednisolone or methylprednisolone) tapered over weeks.
• Ophthalmoplegia: may take weeks–months to recover. Physiotherapy and supportive eye care help function.
• Relapse prevention: slow taper and careful follow-up to monitor recurrence.
• Secondary cases: treat underlying malignancy/infection/inflammatory disease if identified.
• Symptomatic: analgesia for pain, manage diplopia (e.g., prism lenses or patching).

Prognosis

• Most patients respond well to steroids with full or near-complete recovery.
• Relapses occur in up to 40% — long-term monitoring is essential.
• Delay in treatment increases risk of persistent ophthalmoplegia and morbidity.

Conclusion

Tolosa-Hunt Syndrome is an important but rare cause of painful ophthalmoplegia. It is largely a diagnosis of exclusion. Rapid steroid responsiveness is a hallmark, but careful workup is mandatory to exclude cavernous sinus thrombosis, aneurysm, or tumour.

References

• Hunt JW. Ophthalmoplegia and retrobulbar neuritis with idiopathic cavernous sinus inflammation. Arch Neurol. 1954.
• Tolosa J. Periarteritic lesions of the cavernous sinus. J Neurol Neurosurg Psychiatry. 1954.
• De Angelis F, et al. Tolosa-Hunt Syndrome: comprehensive review. Autoimmun Rev. 2017.
• Michelson DB. Diagnosis & management of Tolosa-Hunt. Curr Opin Neurol. 2005.
• International Headache Society. ICHD-3 classification. Cephalalgia. 2018.