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Department of Pharmacy Practice, Sri Venkateshwara College of Pharmacy, Madhapur, Hitech City Road-86, Hyderabad, Telangana, India
Tolosa–Hunt syndrome is a rare granulomatous inflammatory disorder of the cavernous sinus characterized by unilateral orbital pain and ophthalmoplegia. We report a case of a 54-year-old female presenting with acute painful ophthalmoplegia localized to the left cavernous sinus. Contrast-enhanced magnetic resonance imaging revealed subtle asymmetric enhancement of the cavernous sinus. Extensive laboratory and cerebrospinal fluid investigations excluded infectious, vascular, and neoplastic causes. The patient showed rapid clinical improvement following corticosteroid therapy, supporting the diagnosis of Tolosa–Hunt syndrome. This case highlights the significance of early recognition, clinicoradiological correlation, and careful exclusion of mimicking conditions
Tolosa–Hunt syndrome (THS) is a rare idiopathic granulomatous inflammatory disorder that affects the cavernous sinus, superior orbital fissure, or orbital apex, characterized clinically by unilateral orbital pain and ipsilateral ophthalmoplegia.[1] Initially described by Tolosa in 1954 and then further detailed by Hunt and colleagues in 1961, the syndrome remains a rare but significant cause of excruciating cranial neuropathies.[2]
According to the International Classification of Headache Disorders, Third Edition (ICHD-3), THS is currently categorized as a painful cranial neuropathy caused by granulomatous inflammation of the cavernous sinus or associated structures.[3] The cranial nerves III, IV, and VI are most commonly affected, with occasional sensory impairment in the ophthalmic division of the trigeminal nerve (V1).[4] The abducens nerve is especially susceptible due to its medial course within the cavernous sinus.[5] Unless the inflammatory process spreads to the optic nerve at the orbital apex, visual acuity is typically maintained.[6]A crucial part of the diagnosis process is magnetic resonance imaging (MRI) with contrast, which frequently shows asymmetric cavernous sinus enlargement or enhancement.[7] However, imaging findings may be subtle or nonspecific, and THS remains fundamentally a diagnosis of exclusion.[8] Cavernous sinus thrombosis, neoplasms (such as lymphoma or meningioma), intracavernous carotid aneurysm, sarcoidosis, tuberculosis, and invasive fungal infections are important differential diagnoses.[9]
A hallmark feature of THS is its rapid and often dramatic response to corticosteroid therapy, frequently resulting in relief of pain within 24 to 72 hours.[2,10] Well-documented case reports remain valuable in highlighting the significance of clinicoradiological correlation and reaffirming clinical recognition, despite the diagnostic complexity and recurrence potential. We report a case of unilateral painful ophthalmoplegia with subtle imaging findings and marked steroid responsiveness consistent with Tolosa–Hunt syndrome, emphasizing the importance of early diagnosis and exclusion of secondary causes.
CASE REPORT:
Patient Information
A 54-year-old female presented to the Neurology Department with acute onset of severe left-sided headache, which was aggravated by exposure to light and associated with two episodes of vomiting. She also complained of left eye pain and diplopia of one-day duration. Her medical history was significant for diabetes mellitus, newly diagnosed hypertension and herpes simplex virus (HSV) keratitis for the past three years. She was on Cilnidipine 10mg, Acyclovir 400mg and Glycomet-GP1 (500/1mg). There was no history of smoking or head trauma.
Clinical Findings
On examination, the patient was conscious, oriented and obeying commands. Ocular examination of the left eye revealed painful ophthalmoplegia characterized by limitation of abduction, ptosis, and anisocoria, with sluggish pupillary reaction to light (Figure 1). Visual acuity was preserved bilaterally and fundus examination was normal. There was no relative afferent pupillary defect. Neurological examination demonstrated left abducens nerve palsy along with hypoesthesia in the distribution of the ophthalmic division of the trigeminal nerve. Examination of the right eye and other systemic evaluations were unremarkable, and there was no fever or additional focal neurological deficit.
Figure 1: Left-sided ptosis with restricted abduction and anisocoria consistent with painful ophthalmoplegia.
Diagnostic Assessment
Hematological evaluation revealed mild leukocytosis (12,340/mm3) and thrombocytosis (426,000/mm3), with a hemoglobin level of 13.1g/dL. Glycemic control was poor, as indicated by an elevated HbA1c of 9.45%. Other biochemical parameters, including renal function tests, lipid profile, and serum electrolytes, were within normal limits. Cerebrospinal fluid (CSF) analysis showed elevated glucose levels (100mg/dL) with normal protein and lactate dehydrogenase levels. Microbiological investigations, including CSF culture and sensitivity, Gram stain, fungal stain, and GeneXpert for tuberculosis, were negative. Serological testing for human immunodeficiency virus and hepatitis viruses was non-reactive.Magnetic Resonance Imaging (MRI) of the brain and orbit with contrast demonstrated asymmetric enhancement of the left cavernous sinus with extension into the superior orbital fissure and orbital apex (Figure 2). There was no evidence of thrombosis, neoplasm, or abscess. These findings, in conjunction with the clinical presentation and exclusion of secondary causes, were suggestive of a granulomatous inflammatory process consistent with Tolosa–Hunt syndrome. Based on clinical presentation, imaging findings, and exclusion of secondary causes, a diagnosis of Tolosa–Hunt syndrome was made.
Figure 2: A) Axial contrast-enhanced MRI demonstrating mild asymmetric enhancement and fullness of the left cavernous sinus (red arrow), consistent with inflammatory involvement.
B) Coronal MRI demonstrating extension
into the orbital apex (yellow arrow).
Treatment
The patient was initiated on high-dose intravenous methylprednisolone at a dose of 1 gram/day for five days, along with supportive management including pantoprazole, intravenous fluids and protective eye care with patching. She showed rapid symptomatic improvement, particularly in headache and ocular pain, without progression of neurological deficits. She was discharged on the fifth day in a stable and improving condition. Oral prednisolone at a dose of 50 mg daily was prescribed for one week, followed by a gradual tapering regimen with a reduction of 10mg per week until a maintenance dose of 10mg daily was reached. She was advised strict blood glucose monitoring due to corticosteroid therapy and instructed regarding eye protection and warning symptoms.
Outcome and Follow-up
At discharge, the patient demonstrated significant clinical improvement with reduction in pain and stabilization of ocular findings. She was advised regular follow-up to monitor for recurrence, given the known relapsing nature of Tolosa–Hunt syndrome, and to ensure adequate glycemic control during steroid therapy. At one-month follow-up, the patient continued to show sustained improvement with no recurrence of symptoms or new neurological deficits. She was further advised to continue periodic follow-up, considering the potential for future relapse, and instructed to seek immediate medical attention if symptoms such as worsening headache, visual disturbances, or recurrence of diplopia occurred.
DISCUSSION
Painful ophthalmoplegia represents a neurological emergency requiring prompt anatomical localization and systematic exclusion of secondary causes. Our patient was precisely localized to the cavernous sinus due to the combination of unilateral orbital pain, isolated abducens nerve palsy, and hypoesthesia in the ophthalmic division of the trigeminal nerve. [4] The cavernous sinus contains cranial nerves III, IV, V1, V2, and VI, making it particularly vulnerable to inflammatory and compressive pathologies. [4] According to several clinical series, the abducens nerve's medial anatomical location explains why it is frequently involved in THS.[5,11]According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), the diagnostic criteria for Tolosa–Hunt syndrome are summarized in Table 1. [3] The headache in our patient was localized around the ipsilateral orbital region and arose prior to the onset of cranial nerve VI palsy within the specified two-week period. Asymmetric cavernous sinus enhancement was seen on contrast-enhanced MRI, and vascular, neoplastic, and infectious causes were ruled out by thorough investigations. Thus, our case fulfilled the ICHD-3 diagnostic criteria for Tolosa–Hunt syndrome.
|
Table 1: The International Classification of Headache Disorders (ICHD) criteria for THS include the following: [3] |
|
|
A. |
Unilateral headache fulfilling criterion C |
|
B.
|
Both of the following: 1. granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy 2. paresis of one or more of the ipsilateral III, IV and/or VI cranial nerves |
|
C.
|
Evidence of causation demonstrated by both of the following: 1. headache has preceded paresis of the III, IV and/or VI nerves by ≤2 weeks, or developed with it 2. headache is localized around the ipsilateral brow and eye |
|
D. |
Not better accounted for by another ICHD-3 diagnosis. |
Neuroimaging serves a supportive but not definitive role. Contrast-enhanced MRI typically demonstrates asymmetric enhancement or enlargement of the cavernous sinuses. [7] Enhancement and convexity of the cavernous sinus's lateral wall were frequent findings in a radiological series by Cakirer et al., however early or mild disease may only exhibit subtle changes. [7] Anatomically, our patient's neurological deficits were consistent with the mild asymmetric enhancement of the left cavernous sinus with extension toward the orbital apex. An inflammatory etiology rather than a neoplastic or infectious one was supported by the lack of mass effect, thrombosis, or destructive changes. Importantly, normal or subtle imaging findings do not exclude Tolosa–Hunt syndrome, particularly in early stages, and clinical correlation remains essential. he most important component of evaluation remains differential diagnosis. Neoplasms may exhibit progressive deficits and distinct radiological patterns; granulomatous disorders like sarcoidosis or tuberculosis require serological or microbiological confirmation; and cavernous sinus thrombosis often presents as systemic toxicity and rapid progression.[8,9,12] In diabetic patients, invasive fungal sinusitis must also be considered. [9] In the present case, the probability of these conditions was considerably decreased by the absence of fever, negative cerebrospinal fluid analysis, normal serological workup, and radiological evidence of vascular or space-occupying pathology.True orbital apex syndrome and optic nerve involvement were further refuted by preserved visual acuity and the lack of a relative afferent pupillary defect.[6] This distinction is clinically relevant, as optic neuropathy may indicate a more extensive inflammatory or compressive process necessitating alternative management considerations.Steroid responsiveness remains a defining feature of THS. Hunt et al. initially reported rapid pain relief following corticosteroid therapy, a finding subsequently reinforced in later case series. [2,10] High doses of intravenous methylprednisolone rapidly alleviated our patient's headache and ocular pain without triggering a neurological deficit to worsen. Although steroid response alone is not pathognomonic, it does provide strong support for the diagnosis when combined with appropriate imaging and careful exclusion of secondary causes.Recurrence has been reported in approximately 30–40% of patients, occasionally years after the initial episode.[13] Long-term follow-up is therefore recommended. In our patient, poorly controlled diabetes mellitus presented as an additional management challenge. This required careful monitoring of blood sugar levels during corticosteroid therapy. This highlights the importance of personalized treatment strategies for inflammatory cavernous sinus syndromes.In summary, this case emphasizes three key principles. First, precise neuroanatomical localization is crucial for evaluating painful ophthalmoplegia. Second, subtle MRI findings should not rule out THS when clinical features strongly suggest it. Finally, it is vital to thoroughly rule out similar conditions before starting corticosteroid therapy. Early recognition of Tolosa–Hunt syndrome is crucial, as prompt corticosteroid therapy can prevent unnecessary investigations and reduce patient morbidity.
CONCLUSION
Tolosa–Hunt syndrome should be considered in patients presenting with unilateral painful ophthalmoplegia after careful anatomical localization and exclusion of secondary causes. When clinical features strongly localize to the cavernous sinus, subtle radiological findings do not rule out the diagnosis. Before initiating corticosteroid therapy, a thorough evaluation remains necessary to rule out infectious, vascular, and neoplastic etiologies. Favourable short-term outcomes along with rapid symptom relief can be achieved with early detection and corticosteroid therapy. Given the possibility of recurrence and the possible metabolic effects of corticosteroid therapy, especially in patients with comorbid conditions like diabetes mellitus, long-term follow-up is strongly recommended.
REFERENCES
O’Connor P, et al. Recurrence in Tolosa–Hunt syndrome. J Neurol. 2009;256:134-139.
Shirisha Vodnala, Alice Melinda, Srujan Kotha, Divya Dharavath, Sathwika Vudugula, Tolosa–Hunt Syndrome Presenting As Painful Ophthalmoplegia: A Clinicoradiological Case Report, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 4, 4793-4798, https://doi.org/10.5281/zenodo.19881841
10.5281/zenodo.19881841