From left to right: an unusual presentation of Tolosa-Hunt syndrome with bilateral eye involvement.

Here we discuss a presentation of Tolosa-Hunt syndrome (THS) in a 44-year-old female with new right-eye ptosis, ophthalmoplegia and headache. Four days prior, she had almost identical ptosis and ophthalmoplegia in her left eye, which resolved. Cavernous sinus inflammation and symptom improvement with glucocorticoid treatment indicated THS with bilateral eye involvement, a presentation which may be undervalued by the current THS classification.

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.

Tolosa-Hunt syndrome with general myasthenia gravis involvement.

Tolosa-Hunt syndrome is an uncommon disease that exhibits unilateral periorbital pain or headache, accompanied by cranial nerve palsies. Myasthenia gravis is an acquired immune system disease involving the neuromuscular junction. One rare case of Tolosa-Hunt syndrome combined with ocular myasthenia gravis had been reported in the literature, but not general myasthenia gravis. We present a patient with a probable coincidence of Tolosa-Hunt syndrome and general myasthenia gravis. A 63-year-old male exhibited episodes of unilateral headache with double vision, bilateral ptosis, vision decrease in the left eye and left facial hypoesthesia, muscle weakness in limbs and neck. The muscle weakness was fluctuating and could be relieved by rest. Blood analysis, cranial magnetic resonance imaging, magnetic resonance angiography/venogram) and orbit/mediastinum computed tomography demonstrated no abnormalities. Serum myasthenia gravis related antibodies detection showed positive titin- antibodies and ryanodine receptor antibodies. Corticosteroid and pyridostigmine bromide treatments were effective. Each of the patient's symptoms had almost disappeared at the third-month follow-up. We speculate on the etiology of Tolosa-Hunt syndrome with general myasthenia.

Use of methotrexate in the management of recurrent Tolosa-Hunt syndrome: Two case reports.

RATIONALE: Tolosa-Hunt syndrome (THS) is rare condition characterized by painful ophthalmoplegia that usually responds well to corticosteroid. About a half of THS patients experience recurrence within intervals of months to years from initial presentation. Recurrence is more common in younger patients, and can be ipsilateral, contralateral, or bilateral. Cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, infliximab, and radiotherapy can be considered as second-line treatment. However, there is insufficient evidence for treatments preventing recurrence of THS. PATIENT CONCERNS: We experienced two patients with THS that recurred twice while tapering or after ceasing corticosteroid administration. DIAGNOSIS: Both patients were diagnosed as recurrent THS. INTERVENTIONS: Methotrexate was treated with a combination of corticosteroid after THS recurred twice with corticosteroid therapy alone. OUTCOMES: After adding methotrexate to the steroid regimen, their symptoms were successfully regulated and ceased to recur LESSONS:: These cases add to the evidence for the use of methotrexate as a second-line therapeutic agent for those patients with recurrent THS attacks. Further studies are in need to prove the risk and benefits of second-line treatments in THS.

Recurrent Painful Ophthalmoplegic Neuropathy with Residual Mydriasis in an Adult: Should it Be Classified as Ophthalmoplegic Migraine?

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare condition that manifests as headache and ophthalmoplegia. It typically occurs in children. Although migraine or neuropathy have been suggested as etiologies, the precise etiology remains unclear. In the International Classification of Headache Disorders 3rd edition-beta version (ICHD3ß) (code 13.9), RPON was categorized into painful cranial neuropathies and other facial pains. We encountered a 48-year-old woman who had diplopia and right ptosis. The administration of prednisolone led to the immediate improvement of her oculomotor palsy, but residual mydriasis remained. Based on this case, the pathophysiology of RPON may involve temporary nerve inflammation with migraine. Repeated and severe migraine attacks may cause irreversible nerve damage. Thus, medication for migraine prophylaxis might be needed to prevent RPON.

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.

Isolated trochlear nerve palsy in Tolosa-Hunt syndrome.

A 67-year-old Japanese woman without contributory medical history developed acute onset of left-sided trochlear nerve palsy (TNP) with persistent and severe periorbital pain. There were no other neurological abnormalities. Funduscopic findings were normal. Cranial and orbital magnetic resonance (MR) imaging, and cranial MR angiography demonstrated no abnormalities. By administration of prednisolone 40 mg/day from the day after onset, periorbital pain was resolved within 24 hours, and TNP within 5 days. Thereafter, prednisolone was gradually tapered off. She remained asymptomatic under no medication. In the English language literature, this is the first reported case of Tolosa-Hunt syndrome presenting with isolated TNP.

[Tolosa-Hunt syndrome]. / A Tolosa-Hunt-szindróma.

Both men and women are affected by the rare disease called Tolosa-Hunt syndrome. We don't know exactly what causes it to evolve. It is usually put into the categories of either idiopathic inflammation or pseudotumor. Its pathological feature is a non-specific inflammatory process with fibroblastic, lymphocytic, plasmocytic infiltration, which can be found, for the most part, in the wall of the sinus cavernosus. Granulocytic and giant-cell infiltrations have been described too. The possibility of autoimmune disease has also come up. In our current study we describe the case of a female patient who recovered with the help of a steroid therapy. Through examining her, we also found immunological alterations, which should urge us to thoroughly examine the further observations of this kind.

The Tolosa-Hunt syndrome in children: a case report.

Tolosa-Hunt syndrome (THS) is characterized by unilateral painful ophthalmoplegia with oculomotor paresis, associated with an idiopathic granulomatous inflammation involving the cavernous sinus, with a typical relapsing-remitting course. We report a case of an 8-year-old girl who was admitted because of an ophthalmoplegia with exotropia and ptosis of the left eyelid, accompanied by diplopia and left sovraorbital pain. The clinical data, neuroradiological findings and response to steroid treatment suggested THS, as defined by the 2004 International Classification of Headache Disorders (ICHD)-II criteria. THS must be considered a possible cause of painful ophthalmoplegia in childhood, as well as in adults, and confirmed with a focused neuroradiological investigation. The few paediatric cases described in the literature that meet the 2004 ICHD-II criteria are not sufficient to identify possible differences between the paediatric and the adult forms. Every new paediatric case should therefore be reported in order to gather and compare further information.

Bilateral painful idiopathic ophthalmoplegia: a case report.

Around 3% of the individuals with painful ophthalmoplegia have bilateral complaints. In the vast majority of these cases, appropriate investigation demonstrates a secondary etiology, and we are not aware of idiopathic cases reported. Herein we report a case of bilateral ophthalmoplegia where extensive investigation did not suggest a secondary cause.

[Long-term risk of relapses in Tolosa-Hunt syndrome]. / Riesgo de recaídas a largo plazo en el síndrome de Tolosa-Hunt.

INTRODUCTION: The reviewed diagnostic criteria of Tolosa- Hunt síndrome (THS) by the International Classification of Headache Disorders (ICHD-II, 2004) includes demonstration of inflammatory changes by magnetic resonance imaging (MRI) in the cavernous sinus region as an alternative to biopsy. Careful follow-up is required to exclude other possible causes of painful ophthalmoplegia. It remains unclear for how long such close observation should be extended to assure the diagnosis nor whether THS represents a self-limited condition in the long-term. CASE REPORT: An observational study along 13 years of a patient fulfilling current ICHD-II criteria for THS to clarify the natural history of the disorder. RESULTS: We witnessed three episodes, the presenting one causing severe left orbital pain, ipsilateral abducens palsy , and hypoesthesia in the territory of the ophthalmic branch of the trigeminal nerve. Gadolinium MRI showed enhancement of tissue infiltrating the lateral wall of the carotid sinus. A relapse 21 months later caused involvement of left oculomotor and abducens nerves in addition to orbital pain which responded rapidly to steroids. Ensuing remission maintained for up to 11 years concluded in a new relapse again characterized by severe ipsilateral orbital pain and frontal numbness, but no ophthalmoplegia. A gadolinium-MRI did not show enhancement on this occasion despite prompt response to steroids. CONCLUSION: The risk of relapses in THS and its response to steroids may be maintained for as long as 13 years.

Riesgo de recaídas a largo plazo en el síndrome de Tolosa-Hunt / Long-term risk os relapses in Tolosa-Hunt syndrome

Introducción. Los criterios revisados por la International Classification of Headache Disorders (ICHD-II, 2004) para el diagnóstico del síndrome de Tolosa-Hunt (STH) exigen demostrar cambios inflamatorios en el seno cavernoso mediante imágenes por resonancia magnética (RM) como alternativa a la biopsia, pero se requiere un seguimiento cuidadoso del paciente que permita excluir otras causas de oftalmoplegía dolorosa. No está clara su duración ni si el proceso es autolimitado en el tiempo. Caso clínico. Estudio observacional a lo largo de 13 años de una paciente que cumplía criterios ICHD-II a fin de clarificar la historia natural del proceso. Resultados. Observamos tres episodios: el primero iniciado con intenso dolor orbitario izquierdo, seguido de parálisis ipsolateral del nervio motor ocular externo e hipoestesia en el territorio de la rama oftálmica del trigémino. Una RM con gadolinio mostró captación por un tejido que infiltraba la pared lateral del seno carotídeo. Sufrió una recaída 21 meses después; ocasiona ahora parálisis de los nervios motor ocular común y motor ocular externo izquierdo, además de dolor orbitario, con respuesta rápida al tratamiento esteroideo. Tras una remisión prolongada 11 años, una nueva recaída se caracterizó nuevamente por intenso dolor orbitario y acorchamiento frontal ipsolateral izquierdos, pero no oftalmoplegía. Una RM con gadolinio no mostró realce en esta ocasión pese a una pronta respuesta a los corticoides. Conclusiones. El riesgo de recaídas en el STH se prolonga al menos durante 13 años, manteniéndose una respuesta favorable a los corticoides (AU)

Introduction: The reviewed diagnostic criteria of Tolosa- Hunt síndrome (THS) by the International Classification of Headache Disorders (ICHD-II, 2004) includes demonstration of inflammatory changes by magnetic resonance imaging (MRI) in the cavernous sinus region as an alternative to biopsy. Careful follow-up is required to exclude other possible causes of painful ophthalmoplegia. It remains unclear for how long such close observation should be extended to assure the diagnosis nor whether THS represents a self-limited condition in the long-term. Case report: An observational study along 13 years of a patient fulfilling current ICHD-II criteria for THS to clarify the natural history of the disorder. Results: We witnessed three episodes, the presenting one causing severe left orbital pain, ipsilateral abducens palsy , and hypoesthesia in the territory of the ophthalmic branch of the trigeminal nerve. Gadolinium MRI showed enhancement of tissue infiltrating the lateral wall of the carotid sinus. A relapse 21 months later caused involvement of left oculomotor and abducens nerves in addition to orbital pain which responded rapidly to steroids. Ensuing remission maintained for up to 11 years concluded in a new relapse again characterized by severe ipsilateral orbital pain and frontal numbness, but no ophthalmoplegia. A gadolinium-MRI did not show enhancement on this occasion despite prompt response to steroids. Conclusion: The risk of relapses in THS and its response to steroids may be maintained for as long as 13 years (AU)

SPIR MRI usefulness for steroid treatment management in Tolosa-Hunt syndrome.

A 40-year-old man underwent surgery for a right middle ear cholesteatoma. One month later, he presented with a subacute ocular pain that was followed one day later by the appearance of vertical diplopia attributable to a right superior rectus paresis, lid ptosis and hypoaesthesia in the territory of the I and the II right trigeminal branches. A fat-suppressed (selective partial inversion recovery, SPIR) gadolinium-enhanced MRI favours the detection of inflammatory pathological tissue inside the right cavernous sinus, and in this patient it suggested a diagnosis of Tolosa-Hunt syndrome. The pain disappeared quickly after steroid treatment was started whereas the ocular nerve involvement improved only slightly during the first week of treatment. After two months, the patient only complained of diplopia on up-gaze, but the therapy was discontinued two months later on the basis of both clinical signs and MRI findings. SPIR MRI may be useful not only to support a diagnosis of Tolosa-Hunt syndrome, but also to follow-up the disease course and to manage steroid treatment.

Paediatric Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome is characterized by a dull, persistent pain around the affected eye, ophthalmoplegia and, sometimes, involvement of other cranial nerves passing through the cavernous sinus. Corticosteroid administration is valuable in the treatment and frequently has a dramatic effect. We report a boy with Tolosa-Hunt syndrome who fails to respond to the initial steroid treatment. The role of the MRI in the management of this condition is discussed.

[Visual cortex in the Tolosa-Hunt syndrome. Functional imaging for the detection of a psychogenic disorder--a case report]. / Visusstörungen beim Tolosa-Hunt-Syndrom. Untersuchung mit der funktionellen Magnetresonanztomographie zur Abgrenzung psychogener Störungen--Ein Fallbericht.

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.