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.

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.

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.

Tolosa-Hunt Syndrome in Childhood and Adolescence: A Literature Review in the Last 10 Years.

OBJECTIVES: The aim of the study is to review the articles published in the last 10 years on Tolosa-Hunt syndrome (THS) in childhood and adolescence to learn about its clinical and epidemiological characteristics and its therapeutic management. METHODS: Based on the literature search in the major medical databases and using the descriptors "Tolosa-Hunt syndrome and children" and "Tolosa-Hunt syndrome and adolescent" we included articles published between 2009 and 2019. We found 51 articles, but only 11 met the inclusion criteria. RESULTS: There were eight women and four men with THS, whose average age was 12.0 ± 4.3 years, ranging from 4 to 17 years. Magnetic resonance imaging showed inflammation in the cavernous sinus (100%), orbit (25%), and superior orbital fissure (8.3%), unilateral in all patients. The internal carotid artery (58.3%), third (66.7%), sixth (33.3%), and fourth (25%) cranial nerves were injured. Headache was located in the orbital region, ipsilaterally to nerve involvement and had mild to severe intensity. Corticosteroid was the treatment used in 91.7% of the patients. They were followed for an average of 13.4 ± 12.4 months. Only two patients had recurrence of the disease. CONCLUSION: THS is infrequent in childhood and adolescence and knowledge of its clinical and epidemiological characteristics and its therapeutic management is necessary for pediatricians.

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: Appraising the ICHD-3 beta diagnostic criteria.

Introduction The term Tolosa-Hunt Syndrome was first used more than half a century ago to describe painful ophthalmoplegia accompanied by cranial nerve palsies. In the decades since, its diagnostic criteria have evolved considerably. The beta version of the 3rd Edition of the International Classification of Headache Disorders narrows these criteria to require the demonstration of granulomatous inflammation on MRI or biopsy. We believe this may introduce challenges to accurate diagnosis. Discussion Requiring the demonstration of granulomatous inflammation for a diagnosis of Tolosa-Hunt Syndrome may introduce the potential for false negative and false positive diagnoses. Although the disorder presents secondary to granulomatous inflammation, MRI technology may not be able to identify it reliably, and biopsy is not always indicated for its symptomatology. Additionally, several cases have been reported of Tolosa-Hunt Syndrome diagnosed with MRI-confirmed granulomatous inflammation that later prove to be attributable to other pathologies. The emphasis on neuroimaging may therefore exclude some true Tolosa-Hunt Syndrome cases and include others resulting from other latent pathologies that are not visible on MRI. Conclusion We wish to offer several potential modifications to the International Classification of Headache Disorders guidelines for Tolosa-Hunt Syndrome, including making the demonstration of granulomatous inflammation on MRI or biopsy non-mandatory and lengthening patient follow-up to two years for cases in which MRI is unrevealing.

Probable Tolosa-Hunt syndrome with a normal MRI.

BACKGROUND: We are reporting a rare case of a 60-year-old woman with a past history of end-stage renal disease and non-Hodgkin lymphoma who presented to our hospital with confusion, unilateral headache, painful ophthalmoplegia and ptosis. The patient was diagnosed clinically with Tolosa-Hunt syndrome (THS). RESULTS: THS is a diagnosis of exclusion. Other diseases were ruled out. Magnetic resonance imaging (MRI) of the brain and orbit was negative twice within a week. The patient was treated with corticosteroids with marked improvement of the orbital pain and headache and mild improvement of the cranial nerves palsy. CONCLUSION: Clinical diagnosis of THS could be supported by radiological findings. According to the International Classification of Headache Disorders (ICHD)-3 beta diagnostic criteria, the diagnosis must be confirmed with an abnormal MRI and/or pathological sample. We add to the previous findings of THS with a normal MRI. Although MRI plays a crucial role in differential diagnosis, it should not, nor should the biopsy, be a must for the diagnosis. Limitations of using MRI in some patients are another problem.

The evaluation of ICHD-3 beta diagnostic criteria for Tolosa-Hunt syndrome: a study of 22 cases of Tolosa-Hunt syndrome.

The objective of the study was to evaluate the amended International Classification of Headache Disorders (third edition, beta version, ICHD-3 beta) with a retrospective analysis. A total of 22 patients diagnosed with painful ophthalmoplegia and Tolosa-Hunt syndrome (THS) in our hospital were retrospectively studied. The following clinical data were collected: symptoms, signs, location of inflammatory tissue, time interval of paresis following the onset of pain, pain and signs of resolution, follow-up and relapse. Pain and diplopia were found in 22 (100 %) and 20 cases (91 %). The sympathetic nerve was involved in 6 cases (27 %). Paresis followed the pain for an average of 8 ± 5.87 days. Serial magnetic resonance imaging (MRI) revealed granulomatous lesion that was visible in 20 patients (91 %). 19 patients (86 %) demonstrated the lesions located in the cavernous sinus, orbital apex or superior orbital fissure. One lesion extended to the intracranial structure. Pain was relieved in 20 cases (91 %) within 72 h and no patient had complete relief from paresis. According to our study, we think the time course of relief should be undefined. Headache location is hard to describe accurately. Normal MRI should be involved in THS diagnoses. The lesion of THS can extend beyond the cavernous sinus and the orbit. The time interval between headache and paresis can exceed 2 weeks.

Orbital apex syndrome secondary to acute invasive fungal rhinosinusitis diagnosed by transnasal endoscopic biopsy of the optic canal:A case report.

Orbital apex syndrome (OAS) is a complex condition characterized by visual loss, diplopia, and eye pain that occurs secondary to several pathological processes involving the orbital apex. We report a case of acute invasive fungal rhinosinusitis (AIFRS) associated with OAS. A 76-year-old man with left-sided visual loss, diplopia, palpebral ptosis, and headache was diagnosed with OAS secondary to Tolosa-Hunt syndrome and received systemic corticosteroid therapy from his neurologist. Owing to persistent symptoms, we opened the optic canal using a transnasal endoscopic approach for a surgical biopsy of the orbital apex lesions. Histopathological evaluation revealed numerous Aspergillus organisms in the biopsied granuloma. After surgical debridement, he received a 12-month course of voriconazole, and no recurrence of AIFRS occurred during 8-year follow-up. Patients with OAS may occasionally be prescribed corticosteroids because the clinical manifestations of AIFRS-induced OAS are similar to those observed in OAS secondary to Tolosa-Hunt syndrome, especially no nasal symptoms which is known to respond to corticosteroid therapy. Because both AIFRS-induced OAS and OAS secondary to Tolosa-Hunt syndrome induce ophthalmoplegia, proptosis, eye pain, it is sometimes difficult to differentiate these two diseases in early stage. However, corticosteroid therapy causes exacerbation of fungal infection in patients with AIFRS-induced OAS resulting in delayed accurate diagnosis and poor prognosis. AIFRS is associated with a high mortality rate ; therefore, transnasal endoscopic biopsy of orbital apex lesions before corticosteroid administration is recommended in patients with OAS. J. Med. Invest. 71 : 310-313, August, 2024.

A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome.

BACKGROUND: Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. METHODS: The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. RESULTS: Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; P 0.05) and have optic nerve dysfunction (56.5%; P 0.05) and longer disease duration (2.3 ± 1.0 months; P 0.05) compared to those with benign THS (mean age, 56.4 years; mean disease duration, 1.6 ± 0.7 months). The patients with additional involvement of both the optic nerve and the second division of the trigeminal nerve experienced a longer disease duration ( P 0.05). Additionally, patients with orbital pseudotumors had diplopia that responded poorly to treatment with glucocorticoids ( P 0.05). High-dose (>0.5 mg/kg/day) and low-dose (≤0.5 mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( P > 0.05). CONCLUSION: Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.

A case review of the MRI features in alternating Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome (THS) consists of a painful ophthalmoplegia with typical features in magnetic resonance imaging (MRI). The recurring nature of this affliction has been known since its first description. However, compromise of the contralateral cavernous sinus, known as alternating THS, is very rare and has never been examined using MRI. We report clinical data, laboratory data and imaging features of a patient with alternating THS. According to our literature review, this is the first MRI study of THS.

Tolosa-Hunt syndrome in a patient with autoimmune hemolytic anemia.

Tolosa-Hunt syndrome is a steroid responsive painful opthalmoplegia due to a nonspecific inflammation of the cavernous sinus. Autoimmune hemolytic anemia is caused by antibodies directed against unmodified autologous red cells. They are both rare conditions. Here we describe the simultaneous occurrence of Tolosa-Hunt syndrome and severe hemolytic crisis in the same patient.

[Tolosa-Hunt syndrome: a case report]. / Tolosa-Huntov sindrom: prikaz bolesnika.

Tolosa-Hunt syndrome is a nonspecific granulomatous inflammation of the cavernous sinus, superior orbital fissure and apex of the orbit. It involves episodes of unilateral orbital pain which may last several weeks, lesions of cranial nerve III, IV or VI, and rarely II, V, VII and VIII. It is characterized by remissions and exacerbations, and can cause permanent neurological disorder of the affected nerves. We present the course of the disease in a patient whose initial symptom was gradual visual loss in the right eye, followed by neuralgic pain in the right orbit and face. The diagnosis was confirmed by biopsy and corticosteroid therapy was administered. Exacerbation of the disease required repeated surgery, excision of the fibrous tissue of the cavernous sinus, as well as prolonged corticosteroid therapy.

Idiopathic Tolosa-Hunt syndrome: four additional cases.

Idiopathic Tolosa-Hunt syndrome (ITHS) is a very rare cause of painful ophthalmoplegia characterized by unilateral orbital pain, ipsilateral oculomotor paralysis and prompt response to steroids. In this paper we report 4 additional cases of ITHS. This rare cause of painful ophthalmoplegia effects the cranial nerves due to a granulomatous lesion of unknown etiology in the cavernous sinus or superior orbital fissure. The International Headache Society redefined the diagnostic criteria for ITHS but it is still mostly a diagnosis of exclusion. Careful evaluation and follow-up is essential for diagnosis. Optimal therapy duration and dosage and prophylactic treatment in recurrent cases needs further research.

Granulomatous pachymeningitis around the sella turcica (Tolosa-Hunt syndrome) involving the hypophysis--case report.

A 50-year-old female presented with right painful abducens nerve palsy persisting for 4 months and mild panhypopituitarism with diabetes insipidus for 6 months. T(1)-weighted magnetic resonance (MR) imaging of the sellar region showed a homogeneously enhanced mass lesion in the right cavernous sinus which seemed to extend from the swollen pituitary gland. T(2)-weighted MR imaging clearly showed the mass in the right cavernous sinus and the thickened dura mater of the sellar floor as hypointense, and the enlarged pituitary gland as isointense. Biopsy of the thickened dura mater and swollen pituitary gland was performed via the transsphenoidal approach. Histological examination revealed inflammation and collagen fiber formation in these regions. The diagnosis was secondary panhypophysitis resulting from granulomatous pachymeningitis involving the cavernous sinus (Tolosa-Hunt syndrome). Corticosteroid therapy was begun after the biopsy. Her periorbital pain and diplopia were relieved, but diabetes insipidus persisted. Follow-up MR imaging showed a decrease in the volumes of the pituitary gland and the mass in the cavernous sinus.

Tolosa-Hunt Syndrome - Case Report.

This case report presents a patient diagnosed with Tolosa-Hunt syndrome (THS) after an extensive neuro-diagnostic and neuroimaging evaluation. Diagnostic work-up included thorough physical and neurological examination, complete laboratory serum assessments, neuroendocrine and immunohistochemistry analysis, cerebrospinal fluid analysis, neurophysiology assessment, ophthalmologist examination and neuroimaging. Th e most important diagnostic tool in deriving the diagnosis of THS was neuroimaging evaluation that included baseline and follow-up cranial contrast enhanced magnetic resonance imaging (MRI). Baseline cranial contrast enhanced MRI detected a nonspecific inflammatory granulomatous lesion in the right cavernous sinus extending basally towards the right trigeminal cave (Meckel's cave) and anteriorly towards the apex of the right orbit. Systemic intravenous high-dose corticosteroid therapy was administered for 3 consecutive days and then tapered down to lower oral steroid doses. Following therapy, the patient experienced complete regression of symptoms. Follow-up cranial contrast enhanced MRI showed significant regression of inflammatory lesion in the area of right cavernous sinus, thus verifying the efficacy of the treatment applied. This paper shows that an extensive diagnostic schedule for THS must be conducted prior to therapeutic treatment, for the possibility of alternative diagnosis. Patients suspected of having THS require careful evaluation, appropriate treatment, and follow-up.

[Tolosa-Hunt syndrome and orbital pseudotumour. Overlapping conditions in a case with an unusual clinical profile]. / Síndrome de Tolosa-Hunt y pseudotumor orbitario. Entidades solapadas en un caso con perfil clínico no habitual.

INTRODUCTION: The origin of Tolosa-Hunt syndrome (THS) and orbital pseudotumour (OP) is not fully understood. It is acknowledged as having an unspecific granulomatous inflammatory nature in different locations. Although there are differences between the clinical features of the two conditions, they also share a number of physiopathogenetic, therapeutic and, in some cases, iconographic similarities. Possible clinical recurrences are common in the two conditions and a broad differential diagnosis is required in all cases. Yet, the association of both processes in the same patient, with radiological proof of the migration of the inflammatory injury, is not frequent. CASE REPORT: We report the case of a male patient with a long history of recurring unilateral painful ophthalmoplegia that was sensitive to steroids; criteria for THS were fulfilled and there was later development of homolateral OP, six years after the onset of his symptoms. The findings in serial studies conducted with magnetic resonance imaging must be highlighted. The patient was submitted to a surgical intervention to treat the orbital injury and a chronic inflammatory process was observed in the fibrotic phase. CONCLUSIONS: Inflammatory pseudotumour and THS perhaps have more points in common than has traditionally been accepted. To our knowledge few cases of the above-mentioned association have been reported in the same patient. When confronted by cases of painful ophthalmoplegia with excessive recurrences the physician must consider the possibility of other alternative diagnoses.