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.

Orbital inflammation following COVID-19 vaccination: A case series and literature review.

PURPOSE: The purpose of the study was to report three cases of orbital inflammation following administration of the COVID-19 vaccination, manifesting as Tolosa-Hunt syndrome (THS) and orbital myositis. METHOD: A retrospective case series and literature review of patients who developed orbital inflammation following a COVID-19 vaccination. RESULTS: One patient presented with Tolosa-Hunt syndrome (THS) 14 days following her third (booster) COVID-19 vaccination, one patient developed orbital myositis 10 days following his first COVID-19 vaccination and one patient developed recurrent orbital myositis 1 and 7 days following her second and fourth COVID-19 vaccination. All patients received the Comirnaty vaccine (Pfizer-BioNTech). A thorough systemic autoimmune disease workup in both patients was unremarkable. Two patients had a prior history of orbital inflammation, with previous involvement of other different orbital structures. Characteristic MRI features for each pathology were observed, supporting the clinical presentation of THS and orbital myositis. There was complete resolution of THS following corticosteroids, with no recurrence at 2 months. Meanwhile, one case of orbital myositis self-resolved at 2 months without use of systemic corticosteroids, while the other patient with orbital myositis required treatment with intra-orbital steroid injections and oral corticosteroids. CONCLUSION: Orbital inflammation has been recognised as a rare adverse effect following COVID-19 vaccination. We present a case series of THS and orbital myositis as varied presentations of this entity.

Frozen overnight: Acute orbital apex syndrome caused by aspergillosis.

PURPOSE: to describe a rare case of orbital apex syndrome caused by aspergillosis with acute presentation. CASE DESCRIPTION: retrospective case report of a 70-year-old man who developed unilateral ophthalmoplegia overnight. He was initially given the diagnosis of suspect Tolosa-Hunt syndrome, but biopsy of the involved tissue showed aspergillosis. CONCLUSION: orbital apex syndrome caused by fungal disease is a life-threatening condition that should be promptly diagnosed and treated. It may present acutely and should not be misdiagnosed as Tolosa-Hunt syndrome. To our knowledge this is the first such case report in the English ophthalmic language Literature.

Síndrome de Tolosa-Hunt una extraña causa de oftalmoplejía dolorosa: reporte de caso / Tolosa-Hunt syndrome a strange cause of painful ophthalmoplegia: case report

RESUMEN INTRODUCCIÓN: El síndrome de Tolosa-Hunt (STH) se caracteriza por una oftalmoplejía dolorosa, de etiología desconocida. De acuerdo con los hallazgos histopatológicos, se ha descrito la formación de un tejido granulomatoso en los senos cavernosos. PRESENTACIÓN DEL CASO: Una mujer de 22 años con cuadro clínico de 3 semanas de evolución caracterizado por cefalea hemicránea derecha, dolor ocular derecho y diplopía. Su examen físico evidenció la existencia de una oftalmoplejía derecha; la resonancia magnética (RM) de silla turca demostró engrosamiento y realce en la región del seno cavernoso derecho. Se presenta el caso clínico de una causa inusual de oftalmoplejía dolorosa. DISCUSIÓN: La oftalmoplejía dolorosa tiene múltiples diagnósticos diferenciales que incluyen causas neoplá-sicas, vasculares, inflamatorias e infecciosas que pueden afectar el seno cavernoso o la fisura orbitaria superior. El STH, que es una causa rara de oftalmoplejía dolorosa, sigue siendo un diagnóstico de exclusión. Por otra parte, se caracteriza por tener una adecuada respuesta al tratamiento con glucocorticoides. CONCLUSIÓN: La negatividad en las investigaciones de las etiologías de oftalmoplejía, los hallazgos imagenológicos en la RM y la adecuada respuesta cínica con el uso de los corticoides permiten confirmar el diagnóstico. No debería ser necesaria la biopsia del seno cavernoso ante la sospecha de STH con adecuada respuesta al manejo corticoide.

ABSTRACT INTRODUCTION: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia of unknown etiology, the formation of a granulomatous tissue in the cavernous sinuses has been described in histopatho-logical findings. CASE PRESENTATION: A 22-year-old woman presenting with 3 weeks of right sided headache, right eye pain and diplopia. Physical examination revealed the existence of a right ophthalmoplegia; magnetic resonance imaging (MRI) of the sella turcica showed thickening and enhancement of the right cavernous sinus. A clinical case of an unusual cause of painful ophthalmoplegia is presented. DISCUSSION: Painful ophthalmoplegia has multiple differential diagnoses that include neoplastic, vascular, inflammatory and infectious causes that can affect the cavernous sinus or the superior orbital fissure. STH is a rare case of painful ophthalmoplegia that continues to be a diagnosis of exclusion characterized by an adequate response to treatment with glucocorticoids. CONCLUSION: The negativity of the investigations for the causes of ophthalmoplegia, the imaging findings in the MRI and the adequate response to corticosteroids allows the diagnosis to be made. Biopsy should not be necessary when THS is suspected and there is an adequate response to corticosteroid management.

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.

Recurrent painful ophthalmoplegic neuropathy: a report of two new pediatric cases.

BACKGROUND: Recurrent painful ophthalmologic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is characterized by repeated attacks of one or more ocular cranial nerve palsies with an ipsilateral headache. While steroid therapy has been reported to be beneficial for attacks, no clear consensus on prophylactic treatments exists. We present two cases emphasizing the diagnostic significance of the loss of enhancement during the symptom-free period and valproate as a beneficial option in prophylaxis. CASE 1: A 4-year-old girl presented with a one-week right frontal headache, vomiting and photophobia. Neurological examination revealed ptosis, oculomotor nerve paresis, and delay in light reflex in the right eye. Brain magnetic resonance imaging (MRI) revealed a 5.5 mm nodular enhancement in the cisternal part of the 3rd cranial nerve in the right premesencephalic area. The enhancement regressed after a 6-month symptom-free period. While propranolol, topiramate and flunarizine were inefficacious in prophylaxis, the patient responded to valproate prophylaxis and benefited from the administration of steroids for one week during the attacks. CASE 2: A 7-year-old girl presented with a ten-day right-sided, throbbing headache in the frontal region, oneday eye deviation and double vision. Neurological examination revealed inward gaze restriction and ptosis in the ipsilateral eye to the headache. Brain MRI revealed a 4.5 mm, enhancing, nodular lesion in the 3rd cranial nerve lodge in the right perimesencephalic area. Her symptoms regressed in one week with dexamethasone and she received prophylactic propranolol. Neuroimaging findings disappeared after a 3-month symptom-free period. After valproate was added because of a relapse, she did not experience any further attacks. CONCLUSIONS: RPON is an uncommon disease in childhood with unknown etiology. On brain MRI with contrast during the symptom-free period, regression of the enhancement or complete resolution of the lesion are guiding features in the diagnosis. Valproate may have beneficial effects on RPON treatment.

Diagnostic controversies in recurrent painful ophthalmoplegic neuropathy: single case report with a systematic review.

BACKGROUND: Ophthalmoplegic migraine, renamed "Recurrent Painful Ophthalmoplegic Neuropathy" (RPON) in 2013 by the International Headache Society is a rare neurologic disorder characterized by recurrent attacks of ophthalmoplegia associated to ipsilateral headache. The etiology is still unknown. Typical magnetic resonance imaging findings show a focal nerve thickening and contrast enhancement. In the majority of cases, there is a full recovery within days or weeks. There is no evidence supporting a specific treatment. The review defines the characteristics of the recurrent painful ophthalmoplegic neuropathy in patients within 2 years of age underlying the importance of the role of magnetic resonance imaging even in presence of the first attack. Thus, an emblematic case report is presented. CASE PRESENTATION: The authors present a case of third cranial nerve paresis in a 17-month-old male child, presenting a neuroradiological pattern highly suggestive of schwannoma, aneurism or recurrent painful ophthalmoplegic neuropathy. Thus, a review of the literature with the pediatric casuistry of recurrent painful ophthalmoplegic neuropathy occurred within 2 years of age focusing on diagnostic considerations is presented. The authors highlight the importance to consider recurrent painful ophthalmoplegic neuropathy in presence of magnetic resonance imaging findings and clinical symptoms referable to aneurysm or schwannoma. Thus, the review defines the characteristics and the neuroradiological findings at the first RPON attack occurred under 2 years of age. CONCLUSION: Although two attacks are necessary, the review strongly suggests to consider recurrent painful ophthalmoplegic neuropathy even at the first attack, in presence of described characteristics and the aforementioned magnetic resonance imaging findings.

Hypopituitarism and cranial nerve involvement mimicking Tolosa-Hunt syndrome as the initially presenting feature of diffuse large B-cell lymphoma: a case report.

BACKGROUND: Early diagnosis of lymphoma involving the central nervous system is sometimes difficult but emergent to avoid the delay of therapeutic initiation. Pituitary insufficiencies are usually associated with lymphoma in the pituitary gland. There have been no cases of lymphoma originating from extra pituitary gland with hypopituitarism that simultaneously presenting unilateral upper cranial nerve palsies and ophthalmalgia. These symptoms are mostly caused by neoplastic involvement of the skull base or benign diseases such as Tolosa-Hunt syndrome (THS). We report a case of lymphoma with unique clinical courses initially presenting hypopituitarism and symptoms mimicking THS with a mass in sphenoidal and cavernous sinuses accompanying sphenoidal bone erosion. CASE PRESENTATION: A 71-year-old woman visited our hospital with left ophthalmalgia, ptosis, and diplopia. Neurological findings revealed left oculomotor, trochlear and abducent nerve palsies. Endocrine tests indicated partial hypopituitarism. Initial CT and MRI revealed that a mass in sphenoidal and cavernous sinuses had invaded the sella with osteolysis of the sphenoid bone. At around four weeks, almost all the symptoms of cranial nerve palsies were relieved. Seven weeks later, she had a high fever and cervical lymph node (CLN) swellings. CLN biopsy revealed CD20-positive B-cells. She was diagnosed with diffuse large B-cell lymphoma (DLBCL). 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) revealed elevated uptake at the erosion lesion of the sphenoidal bone, but not the pituitary gland. After chemotherapy, all the symptoms related to systemic lymphoma were relieved, but partial hypopituitarism remained. The mass in sphenoidal and cavernous sinuses and elevated uptake by PET/CT were dissolved. CONCLUSION: This case of DLBCL had a unique clinical course; initial presentation of hypopituitarism and symptoms mimicking THS. There was also rare demonstration of mass lesions related to DLBCL in the sphenoidal and cavernous sinuses compressing the pituitary gland through an eroded area of the sphenoidal bone. It should be clinically cautioned that DLBCL can be associated with erosion of the sphenoidal bone and cause both hypopituitarism and THS-mimicking symptoms.

Clinical and Cerebrospinal Fluid Characteristics in 55 Cases of Tolosa-Hunt Syndrome: A Retrospective Analytical Study.

BACKGROUND: Several case series of patients with Tolosa-Hunt syndrome have been described in the literature; however, few studies have focused on the cerebrospinal fluid (CSF) characteristics. This study aimed to analyse the CSF characteristics of patients with Tolosa-Hunt syndrome. METHODS: Fifty-five patients who fulfilled the 3rd Edition of the International Classification of Headache Disorders diagnostic criteria for Tolosa-Hunt syndrome were included in this study. We retrospectively analysed data on CSF parameters, imaging findings, and clinical characteristics of these patients. RESULTS: Oligoclonal bands (OBs) were detected in the CSF of 13 (13/44, 29.5%) patients. The sex ratio was balanced. The mean age at onset of Tolosa-Hunt syndrome was 46.9 ± 10.23 (range 22-72) years. Eight (8/13, 61.5%) patients had multiple cranial nerve palsies. Lesions limited to the cavernous sinus were found on magnetic resonance imaging in 7 (7/13, 53.8%) patients. OBs were significantly detected more frequently in patients whose samples were evaluated less than 30 days after the onset of this diseases (p = 0.026); however, there were no significant differences in the protein level (p = 0.360) and IgG synthesis rate (p = 0.614). CONCLUSIONS: The detection of OBs in the CSF of patients with Tolosa-Hunt syndrome was not rare. It would be interesting to follow-up patients with OBs to determine whether they eventually developed an otherwise more specific inflammatory diagnosis.

[A case of recurrent headache and ophthalmoplegia with a contrast-enhanced lesion of the oculomotor nerve in the cavernous region: an atypical phenotype of recurrent painful ophthalmoplegic neuropathy].

The patient was a 14-year-old boy with two previous episodes of self-remitting right ophthalmoplegia with right temporal pain at ages 9 and 12. In 2019, he developed right eyelid ptosis and diplopia 2 days after a pulsating right-sided temporoparietal headache. Recurrent headaches with ophthalmoplegia responded to high-dose steroid therapy, and the clinical features resembled recurrent painful ophthalmoplegic neuropathy (RPON). RPON generally presents with MRI findings of hypertrophy and inflammation at the root of the oculomotor nerve, a vulnerable site of the blood-brain barrier. However, the imaging features in this case were different from those in typical cases of RPON, and oculomotor nerve inflammation was found in the cavernous sinus. The order of onset of headache and oculomotor nerve palsy differed in each recurrence, suggesting that both autoimmune and vascular mechanisms may have been involved in the onset of the disease in our case.