Recurrence and long-term outcomes of Tolosa-Hunt syndrome.

BACKGROUND AND PURPOSE: Tolosa-Hunt Syndrome (THS) is a rare disorder, and detailed clinical information and treatment outcomes have yet to be fully elucidated. This study aims to investigate the clinical features and factors associated with the treatment outcomes of THS, as defined by the established diagnostic criteria. METHODS: This study retrospectively recruited 91 patients with a diagnosis of THS from 2003 to 2020. We analyzed the clinical features and outcomes, the initial treatment response, recurrences, and the final treatment response. RESULTS: Isolated ocular motor nerve palsy was the most common (82.4%) finding of ophthalmoplegia, involving the oculomotor nerve in more than half of the cases (52.0%). The MRI lesions were mostly observed in the cavernous sinus (94.5%) with an extracavernous extension in about one-third of them. Five patients showed only extracavernous lesions. A total of 25 (27.5%) patients experienced recurrence. Recurrence occurred during steroid tapering as part of the initial treatment in seven, while in 18 patients, it happened after the successful termination of the initial treatment. However, all patients achieved complete remission at the final. Age was associated with a decrease in initial symptom duration (HR = 1.023, CI = 1.004-1.044) as well as an increase in recurrence-free duration (HR = 0.944, CI = 0.911-0.978). High-dose corticosteroid treatment was associated with a decrease in initial symptom duration (HR = 1.642, CI = 1.001-2.695) and total treatment duration (HR = 2.203 CI = 1.302-3.730). CONCLUSIONS: THS can recur frequently especially in younger but have a favorable prognosis. High-dose corticosteroids can be an effective initial treatment and reduce the total treatment duration.

Review of Tolosa-Hunt Syndrome, Recent Updates.

PURPOSE OF REVIEW: We aim to present diagnostic considerations and management insights on Tolosa-Hunt syndrome. We highlight recent controversies in this field and emerging literature. RECENT FINDINGS: The diagnostic categorization of Tolosa-Hunt syndrome remains controversial, with imaging negative cases described in the literature and an increasing literature of secondary causes falsely diagnosed as Tolosa-Hunt syndrome. Response to steroids can fulfill diagnostic criteria, but newer management strategies are available in treatment-resistant patients, such as steroid-sparing agents or radiotherapy. Tolosa-Hunt syndrome has become controversial; the entity of granulomatous inflammation of the cavernous sinus and possible extension into orbital fissure and posterior orbit of late has been re-evaluated. Recent case series and reviews have outlined multiple false positive (neoplasm or infection) and negative (no imaging findings) diagnoses. In the future, when assessing whether a patient has this entity, we caution readers to closely follow patients for secondary causes and consider this entity in differential even if MRI is non-revealing. Additionally, biopsy should be regarded as a gold standard for diagnosis and utilized, especially in uncertain cases. The diagnostic categorization of Tolosa-Hunt syndrome may need reconsideration in future versions of the ICHD.

Tolosa-Hunt syndrome and recurrent painful ophthalmoplegic neuropathy, case reports: what to do and when?

BACKGROUND: Tolosa-Hunt syndrome (THS) and recurrent painful ophthalmoplegic neuropathy (RPON) are rare diseases reported within the "Painful lesions of the cranial nerves" section of the International Classification of Headache Disorders-3rd edition (ICHD-3). In case of a first painful attack, differential diagnosis could be challenging and many pitfalls are due to the rarity of the disorders and the lack of information about correct medical management in youngsters. CASE PRESENTATION: Our main purpose was to report a new case of THS and a new case of RPON describing management and diagnostic investigation at the time of the first episode. In both cases of THS (13 years old) and RPON (14 years old) a unilateral periorbital headache associated with acute onset of ipsilateral third cranial nerve paresis, scarcely responding to non-steroidal anti-inflammatory drugs (NSAID), was present at the beginning of the first attack. Brain MRI with "time-of-flight" (TOF) angiography and the need to administer steroids (after 72 h from onset) in order to stop pain were the most important handles allowing us to adopt the correct management both in THS or RPON since onset and to face recurrences in RPON by avoiding useless therapy during follow-up. CONCLUSION: Unilateral periorbital headache associated with third-fourth or sixth cranial nerve paresis should ideally be investigated with a full work-up, comprehensive of brain MRI with TOF angiography since the first attack. In cases with negative brain MRI spontaneous resolution should be considered and watchful waiting might be advisable before starting steroid therapy.

Complete ophthalmoplegia diagnosed as Tolosa-Hunt syndrome on interval MRI.

Tolosa-Hunt syndrome is a rare cause of painful ophthalmoplegia, most commonly presenting with retro-orbital pain and eye motor nerve palsy, most often affecting a single eye. The condition is characterised by an idiopathic process causing granulomatous inflammation to the cavernous sinus affecting, one or multiple cranial nerves that pass therein. The mechanism underlying the inflammation is not well understood, but patients have been observed to respond to steroids during a flare. We present this as a unique case where a multidisciplinary team diagnosed Tolosa-Hunt syndrome despite non-specific MRI findings in the cavernous sinus 1 day following an initially normal MRI.

A 57-year-old man with painful ophthalmoplegia and cavernous sinus involvement: Why this is not Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome (THS) is an idiopathic condition included in the differential diagnosis of painful ophthalmoplegia. Although this was once a common diagnosis, the increasing availability of tests reveals an alternative etiology in many cases. Exclusion of treatable disorders is important, because the prognosis may otherwise be poor. We here describe a patient who presented with painful ophthalmoplegia with an infiltrating lesion in the cavernous sinus. Initially suspected of THS, he had a fatal evolution, and postmortem evaluation revealed cervicocephalic actinomycosis. Actinomycosis diagnosis is often missed, and still represents a challenge to the clinician. We highlight pearls and pitfalls to establish a proper diagnosis to avoid missing a treatable condition in patients with suspected THS.

Tolosa-Hunt syndrome presenting with features of a trigeminal autonomic cephalalgias and pituitary enlargement.

Tolosa-Hunt syndrome is understood as a steroid-responsive, relapsing-remitting, unilateral headache disorder associated with ipsilateral cranial neuropathies, of a probable granulomatous aetiology. The diagnosis is made clinically from the history and examination, supported by appropriate imaging. Here the authors report a case of Tolosa-Hunt syndrome with a headache phenotype mimicking a trigeminal autonomic cephalalgias (hemicrania continua), and serial MRI studies showing a stable enlarged pituitary. Due to her initial lack of clinical signs, she was diagnosed with chronic migraine, revised to hemicrania continua based on indomethacin response, then revised back to chronic migraine. Her final diagnosis was achieved after she developed a left cavernous sinus syndrome 4 years into her disease course. This case shows that Tolosa-Hunt syndrome may present with a non-side-locked headache and delayed development of clinical signs. Clinicians should also maintain a high degree of suspicion when faced with incidental MRI findings.

Recurrent painful ophthalmoplegic neuropathy: a cause for recurrent third nerve palsy in a child.

Recurrent painful ophthalmoplegic neuropathy (RPON), previously called ophthalmoplegic migraine, is a rare condition characterised by recurrent episodes of headache and ophthalmoplegia. We report a case of 11-year-old girl with recurrent painful ophthalmoplegia due to isolated right oculomotor nerve involvement. MR brain imaging showed enhancing lesion of cisternal segment of right oculomotor nerve. A possibility of Tolosa Hunt syndrome was considered and she was treated with glucocorticoids, followed by azathioprine due to recurrence. In the fourth episode, she developed migraine headache followed by right third nerve palsy, after which the diagnosis was revised to RPON. She was started on flunarizine along with short-term glucocorticoids. At 1-year follow-up, she remained asymptomatic. RPON should be considered in patients with recurrent third nerve palsy to avoid inadvertent long-term exposure to immunosuppressive agents.

Multiple Cranial Neuropathies and Pachymeningitis in a Patient With a Pathogenic Nucleotide-Binding Oligomerization Domain 2 Polymorphism.

ABSTRACT: An 11-year-old boy presented with 2 weeks of intermittent headache, right orbital pain, and constant diplopia. Brain MRI showed dural thickening and enhancement of the right lateral cavernous sinus, right orbital apex, and tentorium. Initial cerebral spinal fluid analysis showed only mild pleocytosis, and serum diagnostics were unrevealing. The working diagnosis was Tolosa-Hunt syndrome. His pain and sixth nerve palsy resolved with corticosteroids. Five months after initial presentation, he developed new numbness of the right cheek, complete right ophthalmoplegia, and weakness and numbness of his right hand and leg, all of which were responsive to steroids. Fifteen months later, he returned to the emergency department with 2 weeks of left-sided headaches and acute diplopia. On examination, he had a left cranial nerve 6 palsy. Dural biopsy showed diffuse mononuclear inflammatory cell reaction consisting mostly of lymphocytes with no signs of granuloma formation, nor any epithelioid or giant cells. His clinical course was consistent with an autoinflammatory condition of unknown etiology. Genetic testing with an immunodeficiency panel showed a risk allele in NOD2 (nucleotide-binding oligomerization domain 2) c.3019dup (p.Leu1007Prof*2) that is associated with an increased risk for Crohn disease. His clinical condition had similarities to central nervous system sarcoidosis. Because of the similarities between our patient's clinical, imaging, and genetic findings and neurosarcoidosis, he was switched to a more targeted therapy-infliximab. His condition has since been stable for nearly 2 years. In conclusion, genetic testing should be considered in patients with suspected occult autoimmunity.

Tolosa-Hunt Syndrome: A Case Report.

Tolosa-Hunt Syndrome is a rare disease characterized by painful ophthalmoplegia affecting third, fourth, and/or sixth cranial nerve caused by non-specific inflammation in the cavernous sinus or superior orbital fissure of unknown etiology. We presented a 67-year-old female with Tolosa-Hunt Syndrome. She had a right-sided headache and periorbital pain with double vision. Examination showed right-sided ptosis, right-sided trochlear and abducens nerve palsy, and partial right-sided oculomotor nerve palsy with hypoesthesia in the area of the ophthalmic division of the trigeminal nerve. Magnetic resonance imaging of head and orbit showed altered signal intensity changes in the optic nerve and lateral rectus muscle. After steroid therapy, pain and ptosis were significantly improved in 72 hours. Tolosa-Hunt Syndrome is a diagnosis of exclusion, with clinical presentation, normal investigations, magnetic resonance imaging findings, and response to steroid therapy crucial in making the diagnosis.

Resection of Oculomotor Nerve Lesions Using Continuous Stimulation of the Oculomotor Nerve Proximal to the Lesion: A Technical Report.

BACKGROUND: We describe a continuous monitoring method aimed at preserving nerve function during biopsy of lesions on the oculomotor nerve using stimulation of the oculomotor nerve proximal to the lesion. CASE DESCRIPTION: A 5-year-old girl with a recurrent left oculomotor nerve palsy and contrast-enhancing left oculomotor nerve mass on magnetic resonance imaging underwent a biopsy of the lesion to aid in its diagnosis. At the time of surgery, needle electrodes were inserted into the superior and inferior rectus muscles percutaneously, and cotton-covered electrodes were implanted into the oculomotor nerve proximal to the lesion. Compound muscle action potentials of the oculomotor nerve were measured continuously by monopolar stimulation. The lesion was mapped by direct stimulation, and the unresponsive area was excised. The amplitude of the compound muscle action potentials decreased during the resection but recovered postoperatively. After resection of the lesion, the compound muscle action potentials remained the same as they were preoperatively. No obvious postoperative oculomotor nerve palsy was observed. CONCLUSIONS: This method of continuous monitoring of the function of the oculomotor nerve is simple to use and is suitable for lesions in close proximity to the oculomotor nerve.

Multiple Spontaneous Visceral Arterial Dissections in a Patient With Tolosa-Hunt Syndrome on Corticosteroid Therapy.

Multiple spontaneous visceral arterial dissections are an infrequent occurrence. The etiology, risk factors and natural history of these dissections have not been elucidated, and the optimal therapeutic strategy has not been established. We report a rare case of multiple spontaneous visceral arterial dissections involving the celiac artery, splenic artery, superior mesenteric artery, and right renal artery in a patient with Tolosa-Hunt syndrome on short-term corticosteroid therapy. The patient was subjected to conservative treatment and endovascular repair, achieving good clinical and radiological outcomes during the long-term follow-up period.

Recurrent painful ophthalmoplegic neuropathy revealing oculomotor nerve schwannoma.

Painful ophthalmoplegia is a common presenting symptom in neuro-ophthalmology emergencies. We report an unusual case of a recurrent painful ophthalmoplegia due to a third nerve schwannoma mimicking « ophthalmoplegic migraine ¼. A 18 year-old girl had presented 4 episodes of left eye painful ophthalmoplegia respectively in 8, 13, 16 and 17 years old. One year after the last episode, neurological examination was normal. Brain MRI focused on the oculomotor nerve showed an enhancing nodular lesion suggesting a third nerve schwannoma. Thus, recurrent painful ophthalmoplegia revealing oculomotor nerve schwannoma, as described in our case, is exceptional. To our knowledge, only thirteen cases have been reported in the literature. Third nerve schwannoma is a rare cranial nerve tumor, typically revealed by progressive palsy of the oculomotor nerve. Recurrent painful ophthalmoplegia with persistent headache and enhancement in brain imaging should suggest tumoral lesions.

[Tolosa-Hunt Syndrome; clinical and brain MRI features and treatment]. / Tolosa-Hunt Sendromu; klinigi, kranyal MR özellikleri ve tedavisi.

Tolosa-Hunt Syndrome (THS) is an idiopathic condition characterized by periorbital and hemicranial pain, ipsilateral oculomotor and sixth cranial nerve involvement, good response to steroids, granulomatous inflammation of the cavernous sinus or the top of the orbita. A 25 year- old- male patient presented with severe burning burn pain near the left eye with double vision. The left eye exhibited semiptosis, limited outward gaze, and difficulty in the downward outward gaze. No history of trauma or drug use was reported. Cranial Magnetic Resonance Imaging (MRI) showed thickening cavernous sinus walls to the left, while contrasted MRI sections suggested inflammation as indicated by intense staining. Cerebral arterial and venous angiography were normal. Parenteral treatment with 1mg/kg methylprednisolon commenced. The pain passed on the third day of treatment. Ophthalmoplegia began improving in the third week. The clinical symptoms were completely over after the third month of the clinic. The pain did not recur after corticotheraphy started. The cranial MRI of the patient was reviewed in a comparative perspective in the first and third months of the clinic. Inflammation was observed to get better. THS should always be considered in painful ophthalmoplegia cases. Cranial MRI towards the cavernous sinus, in particular, would suffice for diagnosis, provided that the vertex of orbita is not affected.

Proposed modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy: Five case reports and literature review.

BACKGROUND: Recurrent painful ophthalmoplegic neuropathy (RPON) is an uncommon disorder characterized by recurrent unilateral headache attacks associated with ipsilateral ophthalmoplegia. We intend to study the clinical picture in our case series along with the published literature to discuss the pathogenesis and propose modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy. METHODS: We reported five cases diagnosed as ophthalmoplegic migraine/RPON in our medical centers and reviewed the published literature related to RPON from the Pubmed database between 2000 and 2020. In one of these cases, a multiplanar reformation was performed to look at the aberrant cranial nerve. RESULTS: The mean onset age for RPON was 22.1 years, and the oculomotor nerve was the most commonly involved cranial nerve (53.9%) in 165 reviewed patients. In most patients, ophthalmoplegia started within 1 week of the headache attack (95.7%, 67/70). Additionally, 27.6% (40/145) of patients presented enhancement of the involved nerve(s) from MRI tests. Finally, 78 patients received corticosteroids, out of which 96.2% benefited from them. CONCLUSION: This is the first time multiplanar reformation has been performed to reveal the distortion of the oculomotor nerve. Modified diagnostic criteria are proposed. We hope to expand the current knowledge and increase the detection of recurrent painful ophthalmoplegic neuropathy in the future.