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.

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.

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.

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.

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.

The aetiologies of unilateral oculomotor nerve palsy: a clinical analysis on 121 patients.

Background and purpose: To strengthen the understanding, increase the early diagnostic rate, and improve the outcome of unilateral oculomotor nerve palsy through the analysis of the 121 patients suffering from this disease in our hospital. Methods: A retrospective study was performed on the 121 patients with unilateral oculomotor nerve palsy diagnosed at the Affiliated Hospital of Xuzhou Medical University from October 2014 to October 2015. The clinical data, such as gender, age, aetiology, clinical features, laboratory tests, and six months follow up reports were analyzed. Results: The main causes identified in the 121 patients with unilateral oculomotor nerve palsy were intracranial aneurysm (29.8%), diabetic peripheral neuropathy (26.5%), painful ophthalmoplegia (9.9%), and other causes (33.9%). The results from the six month follow up showed that in all the patients, 53.7% were fully recovered, 38.0% improved, and 8.3% had no significant change in symptoms. The results also indicated that the patients with diabetic peripheral neuropathy had the best outcome with 71.9% full recovery rate, which was significantly higher than that in the patients with intracranial aneurysm (36.1%, p < .05), and idiopathic causes (44.5%, p < .05). Conclusions: Our data indicates that intracranial aneurysm is the leading cause of unilateral oculomotor nerve palsy, and that diabetic peripheral neuropathy has better outcome. Understanding the common causes and clinical features of unilateral oculomotor nerve paralysis is helpful for its early diagnosis and treatment.

Tolosa-Hunt Syndrome / Síndrome de Tolosa-Hunt

Abstract We present a case study of Tolosa-Hunt syndrome, a rare idiopathic disease, that is characterized by painful ophthalmoplegia of strong intensity, generally affecting the third cranial nerve, and, less frequently, the fourth or the sixth cranial nerves. Usually, there is no visual impairment. The treatment is based on corticosteroids with satisfactory results in most cases although recurrences can occur at intervals from months to years. In our case, the patient presented sudden pain periorbital associated with cranial nerves involvement, which have an excellent outcome after treatment with corticosteroids, with no relapses until today.

Resumo Nós apresentamos um caso de Síndrome de Tolosa-Hunt, uma doença idiopática rara, caracterizada por oftalmoplegia dolorosa, de forte intensidade, geralmente afetando o terceiro par craniano, e, menos frequentemente, o quarto e/ou o sexto par. Geralmente, não há acometimento visual. O tratamento é feito com base em corticóides com resultados satisfatórios na maior parte dos casos, embora recorrências possam ocorrer após meses a anos. Relatamos caso de paciente masculino de 36 anos, com diagnóstico prévio de sífilis congênita e esquizofrenia, com dor periocular súbita associada com envolvimento de pares cranianos, que teve melhora total após vigência de corticoterapia, sem recorrências até a presente data.

Síndrome de Tolosa Hunt / Tolosa-Hunt syndrome

RESUMEN El síndrome de Tolosa-Hunt es una entidad poco frecuente cuya etiopatogenia y mecanismos fisiopatológicos se mantienen controversiales. La cefalea asociada a parálisis de uno o más pares craneales, así como diplopía, estrabismo y ptosis palpebral causan un gran temor en el paciente que la padece. Su diagnóstico es por exclusión. Con el objetivo de describir y actualizar el conocimiento sobre esta enfermedad se presenta el cuadro de una paciente que acudió a consulta por cefalea marcada y dolor retroocular. Los hallazgos clínicos y la resonancia magnética confirman el diagnóstico del síndrome de Tolosa Hunt (AU).

ABSTRACT The Tolosa-Hunt syndrome is a few frequent entity whose etiopathogeny and physio-pathological mechanisms are still controversial. The headache associated to the paralysis of one or more cranial paired nerves, and also diplopia, strabismus, and palpebral ptosis cause a great fear in patients suffering it. Its diagnosis is by exclusion. With the objective of describing and up-dating the knowledge on this disease, it is presented the history of a patient who assisted the consultation because of remarked headache and retro-ocular pain. The clinical findings and magnetic resonance confirm the diagnosis of Tolosa-Hunt syndrome (AU).

Tolosa-Hunt Syndrome and Ocular Myasthenia: A Rare Coexistence or Real Association.

Tolosa- Hunt syndrome is a rare steroid responsive disorder caused by granulation tissue involving the cavernous sinus or superior orbital fissure presenting as painful ophthalmoplegia and facial pain. In this report, we describe coexistence of Tolosa-Hunt syndrome with ocular myasthenia which may point towards an autoimmune etiological basis behind the cavernous sinus granulation tissue formation and also offered therapeutic challenge to ameliorate the symptoms.

Steroid-responsive painful ophthalmoplegia: Tolosa-Hunt syndrome, Eales disease, or both?

Introduction Tolosa-Hunt syndrome (THS) is one of the most common 'benign' causes of painful ophthalmoplegia. Diagnosis is based on clinical and imaging findings and the exclusion of other causes because there is no specific biomarker for the syndrome. Eales disease, an idiopathic inflammatory venous disease that primarily affects the eye, can also affect the central (as stroke or myelitis) and peripheral nervous system. Case report We report the case of a 32-year-old woman with a subacute left ophthalmoplegia and evidence of a gadolinium-enhanced lesion suggesting an inflammatory granuloma that resolved within 48 hours after treatment with steroids. A diagnosis of THS was considered at this time. On a follow-up ophthalmological examination, a diagnosis of Eales disease with involvement of the left eye was made. The patient was treated successfully. Conclusion Eales disease could be a cause of painful ophthalmoplegia and may mimic THS. Long-term follow-up of patients diagnosed with THS may be necessary to exclude other diagnoses.

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.

Not all headaches are migraines.

A 40-year-old Somali woman presented features of a right-sided cavernous sinus syndrome which was confirmed with neuroimaging. Although initial investigations were equivocal for an infectious etiology, subsequent investigations led to a diagnosis of tuberculosis as the cause for right-sided cavernous sinus syndrome. This case illustrates that, although the incidence of tuberculosis cavernous sinus syndrome is reportedly low, patients originating from tuberculosis endemic regions warrant scrupulous investigations in order not to miss the diagnosis and effect appropriate treatment.

Cryopyrin-associated periodic fever syndrome manifesting as Tolosa-Hunt syndrome.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. Several reports have demonstrated that the clinical features of THS are not specific to one causal aetiology and can lead to misdiagnosis. CASE REPORT: We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low-penetrance mutation (Q703K) of the cryopyrin/NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome. DISCUSSION: This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin-associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients.

Síndrome de Tolosa-Hunt / Tolosa-Hunt syndrome

RESUMO A Síndrome de Tolosa Hunt é uma doença rara, cuja etiopatogenia é desconhecida. Apresenta-se como uma oftalmoplegia dolorosa de um ou mais nervos cranianos oculomotores, que regride espontaneamente e responde bem ao tratamento com corticoides. O presente estudo trata-se de um relato de caso de um paciente que apresentou seguidos casos de oftalmoplegias dolorosas, envolvendo o nervo oculomotor e o abducente sendo tratado com corticoesteroides obteve uma resposta dramática. Objetiva-se ainda descrever as características fisiopatológicas, clínicas, o diagnóstico diferencial, visto que é um diagnóstico de exclusão, e medidas terapêuticas instituídas de acordo com o International Headache Society 2004 (ISH-2004) através da apresentação do caso clínico conduzido com as normas do estudo supracitado.

ABSTRACT Tolosa Hunt syndrome is a rare disease, whose etiology is unknown. It presents as a painful ophthalmoplegia of one or more oculomotor cranial nerves, which resolves spontaneously and responds well to treatment with corticosteroids. This study is a case report of a patient who had followed painful oftalmoplegias cases involving the oculomotor and abdcens nerves being treated with corticosteroids, obtaining a dramatic response. Another goal is to describe the pathophysiological, clinical, differential diagnosis, since it is a diagnosis of exclusion, and the therapeutic measures adopted according to the International Headache Society 2004 (ISH-2004) by presenting the case study conducted with the standards the study cited above.

Tolosa-Hunt syndrome: an arcane pathology of cavernous venous sinus.

Tolosa-Hunt syndrome, an idiopathic granulomatous inflammation of the cavernous sinus, is primarily a diagnosis of exclusion. The majority of patients present with unilateral orbital pain and features suggestive of paralysis of one or more of the cranial nerves passing through the cavernous sinus and/or superior orbital fissure. MRI of the head may show unilateral enhancement of the cavernous sinus and orbital apex. Treatment is with high-dose intravenous steroids followed by tapering oral steroids. Rapid amelioration of pain within 24-48 h supports this rare diagnosis. Resolution of neuropathies may take longer. We describe a case of a young man who presented with left periorbital pain, complete ophthalmoplaegia and ptosis of the left eye. MRI showed enhancement of the left cavernous sinus and orbital apex. High dose steroids led to complete resolution of pain, while ptosis and ophthalmoplaegia improved gradually.