Bilateral facial nerve involvement in a patient with Tolosa–Hunt syndrome

Abstract

Tolosa–Hunt syndrome is characterized by unilateral retro-orbital headaches and cranial nerve palsies, usually involving cranial nerves III–VI. It is rare for other cranial nerves to be involved, although this has previously been reported. We report a 19-year-old woman presenting with typical features of Tolosa–Hunt syndrome but ultimately developing bilateral facial nerve palsies and enhancement of both facial nerves on magnetic resonance imaging. The patient presented with unilateral retro-orbital headaches and palsies of cranial nerves III–VI. She was diagnosed with Tolosa–Hunt syndrome but was non-compliant with her corticosteroid treatment due to side effects. She returned with progressive left followed by right facial nerve palsy. Her corresponding follow-up magnetic resonance imaging scans showed sequential enhancement of the left and right facial nerves. She ultimately had clinical improvement with IV methylprednisolone. To our knowledge, Tolosa–Hunt syndrome associated with bilateral facial nerve palsy and corroborative facial nerve enhancement on magnetic resonance imaging has not previously been described. Moreover, our patient’s clinical course is instructive, as it demonstrates that this atypical presentation of Tolosa–Hunt syndrome can indeed respond to corticosteroid treatment and should not be mistaken for other entities such as Bell’s palsy.

Introduction

Tolosa–Hunt syndrome (THS) is an idiopathic condition classically characterized by unilateral headaches and ophthalmoplegia. The condition results from inflammation centered within and around the cavernous sinus and usually involving the orbital apex.¹ THS has significant overlap with disorders such as idiopathic orbital inflammation, also known as orbital pseudotumor. Indeed, THS is frequently classified as a variant form of idiopathic orbital inflammation predominantly affecting the orbital apex.² It is possible that these diseases have a shared underlying pathogenesis.³ Nonetheless, THS is clearly a unique disorder with respect to its predilection for the cavernous sinus. When patients present with cranial nerve palsies in the setting of THS, some combination of cranial nerves III–VI is usually affected, sometimes with sparing of the trigeminal nerve branches.⁴ It is extremely uncommon for other, more distant cranial nerves to be affected.⁵

We report rare clinical and neuroimaging findings of lymphoplasmacytic inflammatory involvement of the left facial nerve in a patient with THS. Our patient also developed similar changes in the right facial nerve after 2 months of treatment with oral prednisone. These clinical findings were corroborated by abnormal bilateral facial nerve enhancement on magnetic resonance imaging (MRI). Reports of imaging showing facial nerve involvement in this disease are scarce, and to our knowledge, clinical and imaging evidence of bilateral facial nerve involvement in THS has not previously been described.

Patient presentation and work-up

A 19-year-old woman with no significant past medical history presented with a month of progressive left retro-orbital headaches and photophobia. Two weeks prior to presentation, she had developed acute onset, progressive diplopia. Physical exam at presentation revealed ophthalmoplegia of left cranial nerves III, IV and VI, as well as left V2 distribution sensory loss. Based on these findings, a brain MRI and lumbar puncture were requested, both of which were performed several days after her initial presentation. Her MRI showed abnormal enhancement involving the left cavernous sinus, Meckel’s cave, V2, V3, superior orbital fissure, and left temporal dura (Figure 1(a)–(d)). There was corresponding low T2 signal most prominent in the left Meckel’s cave (Figure 1(e)). Cerebrospinal fluid analysis from her lumbar puncture was normal. To exclude malignancy more definitively, whole body F18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) was requested and performed several days later. This exam showed no findings for malignancy. Incidentally, it did show asymmetric metabolic activity in the right extraocular muscles (Figure 1(f)). This was presumably secondary to palsy of several left cranial nerves.

Figure 1.

Coronal T1-weighted post-contrast images (a)–(d) posterior to anterior, obtained at the time of presentation demonstrate enhancement and enlargement of the left Meckel’s cave (a, arrow), the cavernous sinus (b, solid arrow), V3 (b, dashed arrow), the superior orbital fissure (c, arrow), and V2 (d, arrow). Axial T2-weighted image demonstrates T2 hypointense soft tissue thickening in the left Meckel’s cave and cavernous sinus (e, white arrows) with a normal appearance of Meckel’s cave on the right (e, black arrow). Coronal F18 fluorodeoxyglucose positron emission tomography/computed tomography image through the orbits demonstrates asymmetric radiotracer activity in the right medial and inferior rectus muscles with no uptake on the left (f, arrows).

The patient was started on oral prednisone for presumed THS. Unfortunately, she experienced stomach pain with the medication, and as a result she was initially not fully compliant. Two months later, she returned for follow-up with new left facial muscle weakness and otherwise stable symptoms. Her physical exam revealed a new left facial nerve palsy. A follow-up MRI was performed the next day and showed new enhancement of the left facial nerve (Figure 2(a) and (b)). The previously demonstrated enhancement of the left cavernous sinus was not substantially changed (Figure 2(c)). Given the lack of clinical improvement, biopsy of the enhancing left temporal skull base dura was recommended to exclude neoplasm. This was performed 3 weeks later and showed chronic lymphoplasmacytic inflammatory changes, which are non-specific but compatible with THS. There was no pathological evidence of sarcoidosis, micro-organisms to suggest infection, or IgG4 disease. She was continued on prednisone but remained only partially compliant due to continued stomach pain as a side effect of the medication. She returned several months later with a new right facial nerve palsy and corresponding right facial nerve enhancement on MRI (Figure 2(d)). Currently, her symptoms are well controlled with a corticosteroid regimen of 1000 mg intravenous methylprednisolone weekly with hopes of reducing the dose as tolerated.

Figure 2.

Axial (a) and sagittal oblique (b) T1-weighted post-contrast images 2 months after initial presentation show new enhancement of the left facial nerve extending into the mastoid segment (a–b, arrows). Coronal T1 post-contrast image from the same exam shows persistent enhancement of the left cavernous sinus and V3 (c, arrows). Axial post-contrast image several months later shows new enhancement of the right facial nerve (d, arrows).

Discussion

We report rare clinical and neuroimaging findings of bilateral facial nerve involvement in a patient with THS. Even in its typical presentation, THS can be a challenging diagnosis to make. Ultimately, it is a diagnosis of exclusion, because more sinister or acutely threatening etiologies such as neoplasm or infection can have a similar clinical presentation. In uncertain cases, biopsy may be necessary. Making the correct diagnosis is important because THS is typically responsive to corticosteroids, which is a defining feature of the disease that helps confirm the diagnosis. Imaging plays an important role in the work-up of suspected THS, because it can evaluate the extent of disease, exclude other etiologies for the patient’s symptoms, and assess treatment response on follow-up. It is important for clinicians and radiologists alike to be aware of typical and variant imaging features of this disease.

The hallmark imaging finding in THS is enhancement centered in the cavernous sinus, which may extend anteriorly to the orbital apex and posteriorly to Meckel’s cave. The enhancement frequently has a mass-like appearance, which lends itself to an often unavoidably broad differential diagnosis. Typical differential considerations for THS include meningioma, sarcoidosis, lymphoma, IgG4 disease, infection, pituitary macroadenoma, sinonasal malignancy with perineural tumor spread, metastases, and cavernous sinus thrombosis. Rare lesions such as cavernous sinus hemangiomas can also have a similar appearance.⁶ CT is relatively insensitive in detecting findings of THS, although it can show asymmetry of the cavernous sinuses and enhancement of involved structures. In some cases, contrast enhanced CT can even demonstrate pathological cranial nerve enhancement.⁷ Still, MRI is ultimately the preferred exam both to define the disease extent and exclude potential mimickers. For example, the presence of a normal pituitary gland reliably excludes pituitary macroadenoma. Alternatively, a cavernous sinus mass with a dural tail of enhancement can strongly suggest a meningioma.⁸

Inflammatory changes in THS can often extend contiguously to affect adjacent structures. For example, our patient’s MRI showed enhancement along V2 and V3 (Figure 1 (b) and (d)). Involvement of structures distant from the cavernous sinus or cranial nerves other than III–VI is uncommon. Bilateral facial nerve involvement is an extremely rare manifestation of THS. There have been several prior reports of unilateral facial nerve involvement in THS, generally diagnosed through history and physical exam.^9–11 Very few reports have shown corroborative facial nerve enhancement in THS.¹² To our knowledge, bilateral facial nerve involvement resulting from THS has not previously been described, either on the basis of clinical or imaging findings.

It is important to distinguish THS causing facial nerve palsy from separate etiologies of facial nerve palsy coincidentally occurring in the setting of THS. The latter, although also rare, has previously been reported.¹³ There are several features that can potentially distinguish facial nerve palsy related to THS from other entities. First, the coexistence of retro-orbital pain with facial nerve palsy, as in our patient’s case, would suggest THS with involvement of the facial nerve. Second, MRI demonstrating concomitant cavernous sinus and facial nerve enhancement, as seen on our patient’s imaging, would be supportive of THS causing facial nerve palsy. Finally, clinical evidence of a central rather than peripheral facial nerve palsy would suggest an etiology other than THS.

Corticosteroids are the mainstay of treatment for THS. Oral and intravenous steroids are both effective, with the latter ultimately being used in our patient due to poor tolerance of oral formulations. Notably, our patient was on corticosteroids at the time of the onset of her left facial nerve symptoms, and she did progress to have right facial nerve involvement. However, it is likely that poor medication compliance contributed to her disease progression. For cases in which corticosteroids are truly not sufficient, other immunosuppressive agents, such as methotrexate, have also been used.¹⁴

Conclusion

We have presented novel findings of bilateral facial nerve involvement in a patient with THS. To our knowledge, this has not previously been described. Our patient also illustrates several important clinical lessons. First, given that our patient was not fully compliant with her corticosteroid treatment, it is possible that incomplete treatment led to her disease progression with facial nerve involvement. Second, our patient’s MRI findings demonstrate that THS with facial nerve involvement can mimic other disease processes such as Bell’s palsy, even on imaging. Consideration of all of the clinical and imaging findings, such as headache and cavernous sinus enhancement, are important in making the correct diagnosis. Finally, our patient’s clinical course shows that facial nerve involvement in THS can respond to corticosteroids, as she improved when started on intravenous methylprednisolone.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Consent

Verbal consent was obtained prior to the inclusion of any identifying information or images.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Ajay A Madhavan https://orcid.org/0000-0003-1794-4502

Jared T Verdoorn https://orcid.org/0000-0002-1592-1182