Tolosa-Hunt syndrome as a manifestation of Hypertrophic Pachymeningitis

Dear Editor,

I read the article “Successful treatment of pediatric Tolosa-Hunt syndrome with adalimumab” written by Wiener and Cron (1) and published in a recent issue of the European Journal of Rheumatology, with great interest. Herein, I wish to highlight a possible associated diagnosis of Hypertrophic Pachymeningitis (HP) in their case, which has not been given due consideration. The patient described in this report presented with right-sided hemicranial headache, blurred vision (visual acuity and pupillary reactions not described), and consecutive bilateral abducens palsy. Magnetic resonance imaging (MRI) showed abnormal enhancement of bilateral cavernous sinuses and ipsilateral narrowed internal carotid artery. All these clinical features are that of Tolosa-Hunt syndrome (THS). Additional features like 7^th cranial nerve palsy, pain reaching posterior to the right ear, CSF pleocytosis, persistent dural thickening of the middle cranial fossa on MRI, and multiple dural biopsies revealing patchy chronic inflammation, are all indicative of HP.

HP generally presents with headache, neck rigidity, altered cerebro-spinal fluid composition (high protein content with or without pleocytosis, predominantly lymphocytic), and focal neurological deficits (2–6). Neuroimaging studies reveal focal nodular or diffuse dura mater thickening with diffuse contrast enhancement. Evidence of HP can be found in the region around the tentorium cerebelli, posterior third of the falx, clival dura mater, parasellar, and cavernous region. Depending upon the site of dural inflammation, two patterns of cranial nerve involvement have been described (3). Anterior lesions affecting the cavernous sinus to superior orbital fissure result in a THS like picture, as was seen in the patient described (4, 5). Granulomatous inflammation in the dural layers of the cavernous sinus compress the carotid artery and nerve trunks in the lateral wall of the cavernous sinus. Dense fibrous entrapment and ischemic damage by hypertrophic tissue is the proposed explanation for associated cranial nerve deficits. On the other hand, dural involvement from falcotentorial region to posterior fossa, affects cranial nerves V to XII, and may have associated cerebellar symptoms. The facial palsy and auditory involvement can be attributed to dural inflammation in the middle cranial fossa.

A diagnosis of HP is confirmed only after histopathological examination. HP may be idiopathic or associated with trauma, infections, tumors, autoimmune/inflammatory diseases (including IgG4-related disease), and spontaneous intracranial hypotension. Since tubercle bacilli were isolated, tuberculous HP remains a possible etiology. Another possibility that cannot be ruled out is IgG4 related disease, for which a complete systemic work-up is required. Idiopathic HP can be diagnosed only after extensive investigations rule out other causes.

HP is a chronic condition with multiple remissions and relapses. Response to steroids is variable and systemic immune suppressants are often indicated. Radiation and surgical excision of the involved dura are other options in refractory cases (2, 3, 5, 6).

In conclusion, inadequate clinical and radiological response to steroids in patients with HP should prompt early initiation of systemic immune suppressants.