Bilateral severe Tolosa-Hunt syndrome in an elderly Filipino female: A case report

Bilateral severe Tolosa-Hunt syndrome in an elderly Filipino female: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bilateral severe Tolosa-Hunt syndrome in an elderly Filipino female: A case report Mario Jr Bugay Prado, Angela Apostol-Alday, Karen Joy Adiao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4264469/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Nov, 2024 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 5 You are reading this latest preprint version Abstract Background Only 1–2 per 1,000,000 individuals are diagnosed with Tolosa Hunt Syndrome (THS). While most will present with unilateral symptoms, 4.6% have bilateral involvement, often affecting cranial nerves III, IV and VI incompletely.[ 2 ] Only 2 papers published cases with simultaneous and complete ophthalmoplegia and ptosis, both resolved either spontaneously or with high dose steroids. This case highlights a THS case with bilateral complete cavernous sinus syndrome initially on the right, followed several months later on the left. Case Report: Here we report a 78 years old female who was diagnosed with right sided then followed 3 months later by left sided THS while on low to moderate dose of steroids. She had bilateral painful ophthalmoplegia, hyperesthesia on the ophthalmic and maxillary branches of cranial nerve V and absent direct and consensual pupillary eye reflexes. She had prolonged bilateral R1, R2 and R2’ on blink reflex confirming affection of CN V, and enhancement on the right parasellar area on contrast-enhanced cranial CT indicating presence of granulation tissue. Conclusion THS should be considered in a patient presenting with bilateral painful ophthalmoplegia whether this happens simultaneously or in succession. Pulse therapy or high dose oral steroid is recommended as initial treatment for THS unless there are contraindications. Bilateral Tolosa Hunt Syndrome Cavernous Sinus Syndrome Painful Ophthalmoplegia Figures Figure 1 Introduction Tolosa-Hunt syndrome consists of unilateral orbital or periorbital pain followed within 2 weeks by neuropathy of one of the cranial nerves (CN) in the anterior cavernous sinus, superior orbital fissure or orbital apex, often leading to ophthalmoplegia.[ 4 ] Although the cause remains unknown, it is thought to be induced by granulomatous inflammation or hypertrophic pachymeningitis of the dura surrounding the cavernous sinus.[ 2 ] In the International Classification of Headache Disorders (ICHD) 3 beta, evidence of this inflammation, either through histology or imaging is required to definitively diagnose THS.[ 1 ] Only 1–2 per 1,000,000 individuals are diagnosed with THS.[ 1 ] While most will present with unilateral symptoms, 4.6% have bilateral involvement, often affecting cranial nerves III, IV and VI incompletely.[ 2 ] Only 2 published cases with simultaneous and complete ophthalmoplegia and ptosis, both resolved either spontaneously or with high dose steroids.[ 2 , 3 ] This paper highlights a THS case with bilateral complete cavernous sinus syndrome initially on the right, followed several months later on the left after intake of low to moderate dose of steroids. Case Report The patient was a 78-year-old female, who was admitted for 1 week history of progressively worsening lancinating pain on the right frontal and periorbital area associated with severe dizziness, doubling of vision and drooping of the right eyelid. The past medical, psychosocial and family medical histories were unremarkable. On neurological examination, she was noted to have impaired direct and consensual pupillary eye reflexes, with complete limitation of extra-ocular muscle movement in all directions on the right eye, and hyperesthesia on V1 and V2 areas on the right side of the face. The rest of the neurological and physical examination was unremarkable. Initial plain cranial CT scan, and subsequent cranial MRI with MRA did not show subarachnoid hemorrhage and aneurysm in the circle of Willis or in the cavernous sinuses. However, a repeat cranial CT with contrast done a week later showed enhancement of the right parasellar region on the cavernous sinus (Fig. 1 ) suggestive of Tolosa-Hunt Syndrome. The patient was started on 20mg per day of prednisone which was titrated gradually, as well as gabapentinoids and opioids for the pain. She was subsequently discharged. During follow up, there was minimal improvement of symptoms. Three months later, the patient was re-admitted due to occurrence of, now, severe left frontal and periorbital pain and vomiting. On neurological examination, she was noted to have bilateral abnormal pupillary light reflexes, complete ophthalmoplegia and hyperesthesia on V1 and V2. The rest of examination was unremarkable. A repeat plain cranial CT scan showed normal findings. A blink reflex was done and revealed prolongation of bilateral R1, R2 and contralateral R2 responses, indicating involvement of bilateral V1 portion of cranial nerve V (Table 1 ). Erythrocyte sedimentation rate (ESR) (37 mm/hr, female nv: 3.0 mg/dl) were slightly elevated. Complete blood count, electrolytes, thyroid function test, repetitive nerve stimulation, creatine kinase MM and total, chest x-ray, electrocardiogram and 2D echo were all normal. A cerebral venogram was done and revealed no occlusion of the bilateral cavernous sinus nor evidence of enlarging pituitary mass. A diagnosis of bilateral idiopathic THS was made. Thus, prednisone was immediately increased to 60mg/day. She was subsequently discharged a week later. On follow up, the dizziness and headache significantly improved. There was mild improvement on bilateral upward gaze, but minimal on the rest of the extraocular muscles. Table 1 Blink reflex showing prolonged bilateral R1, R2 and contralateral R2 latencies.[ 5 ] Stimulation Site R1 latency (nv:<9.78ms) R2 latency (nv: <26.8ms) R2’ Latency (nv < 27.2 ms) Left 16.4 33.9 34.4 Right 17.7 35.9 35.2 Discussion The occurrence of retroorbital pain followed by complete ophthalmoplegia, in the presence of granulomatous inflammation on the ipsilateral cavernous sinus detected using imaging study and in the absence of other underlying conditions, is sufficient to confirm the diagnosis of THS.[ 1 , 4 ] Previous diagnostic criteria of International Headache Society (IHS) used to include response to steroids be present. However, this was revised in ICHD3 beta, as steroids was only found to relieve pain but not ophthalmoplegia in most patients.[ 1 ] In theory, it seems expected that the granulation tissue on the cavernous sinus may extend to the ipsilateral superior orbital fissure, orbital apex, sphenoid sinus and middle cranial fossa. On the contrary, there are only few cases reporting complete involvement of the contralateral side.[ 2 – 4 , 6 ] Swiatkowska reported a case of isolated right abducens nerve palsy preceded by retroorbital headache for which the diagnosis of “bilateral” THS was made after the patient was found to have granulomatous inflammation on both cavernous sinuses on imagine.[ 6 ] Kastir and Sugie each reported simultaneous occurrence of THS on both sides which were responsive to high dose steroid and supported by imaging.[ 2 , 3 ] In addition to abnormal enhancement of the granulation tissue, Sugie suspected that idiopathic hypertrophic pachymeningitis (IHP) on both sides may have compressed and induced ischemia of the cranial nerves on the cavernous sinuses, and that THS and IHP share similar pathological features.[ 2 ] Although our case also ended up with bilateral THS, the delayed occurrence of the condition on the left side for about 3 months while on steroid was peculiar. We suspect that the initiation of low to moderate dose of steroid during the initial THS may have reduced the rate of progression of inflammation to the contralateral side. The incidence of THS is 1–2 cases per million individuals, but only 4% will manifest with bilateral and usually incomplete affection of cranial nerves housed in the cavernous sinuses.[ 1 , 4 ] While the cases of Sugie and Kastir manifested with complete ophthalmoplegia, there was no mention of bilateral CN V1 and V2 involvement.[ 2 , 3 ] In classic complete cavernous sinus syndrome, CN III, IV, V1 and V2 embedded in the dura located on the lateral aspect, CN VI near the internal carotid artery (ICA), are all affected. Occasionally, parasympathetic and sympathetic outputs intertwined with CN III and ICA, respectively are also damaged leading to impaired pupillary reflexes.[ 7 ] Thus, aside from being bilaterally affected, our case further demonstrated severe and a complete syndrome making the localization straightforward. Localizing and identifying the syndrome of multiple CN deficits is important as this will narrow down differential diagnosis. The absence of immediate response to steroids in our case may make the THS diagnosis questionable. Accordingly, in ICHD 1 and 2 diagnostic criteria for THS, pain and cranial nerve palsies should resolve within 72 hours after steroid initiation.[ 1 ] However, this latter criterion was removed in the latest guideline as cranial nerve palsies was found to take longer time to improve. Furthermore, response to any drug should not be the basis for diagnosis as several entities such as such as sarcoidosis and lymphoma also present similarly as THS and likewise respond to steroid. In addition, the type, duration and optimal dose of steroid has not been established yet in any large studies.[ 1 ] In our report, the initial steroid dose did not alleviate the pain on the right frontal and periorbital areas, nevertheless, we hypothesize that it could have protracted the involvement of the left. The administration of high dose steroid eventually alleviated the pain; thus, we recommend that pulse therapy or high oral dose (1mg/kg) of steroid be immediately initiated in any case of THS if there are no contraindications. In conclusion, THS should be considered in patients presenting with bilateral painful ophthalmoplegia whether simultaneously or in succession. Pulse therapy or high dose oral steroid is recommended as initial treatment for THS unless there are contraindications. Abbreviations Tolosa-Hunt Syndrome (THS) Cranial nerves (CN) International Classification of Headache Disorders (ICHD) Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP) International Headache Society (IHS) Internal carotid artery (ICA) Declarations Funding: Not applicable Conflict of Interest: The authors declare no conflict of interest Ethics approval: Ethics approval was waived for this report. Consent to participate: Written consent to participate was obtained from the patient. Written consent for publication: Written consent for publication was obtained from the patient. Availability of data and material: Not applicable Code availability: Not applicable Author Contributions: Conceptualization: MP, AAA Data Curation: MP Investigation: MP, AAA and KA, Original Draft: MP, AAA and KA, Review and Editing: MP, AAA and KA. References Dutta P, Anand K. Tolosa-Hunt syndrome: A review of diagnostic criteria and unresolved issues. J Curr Ophthalmol. 2021;33:104–11. https://doi.org/10.4103/joco.joco_134_20 . Sugie K, Morikawa M, Taoka T, Hirano M, Ueno S. Serial neuroimaging in tolosa-hunt syndrome with acute bilateral complete ophthalmoplegia. J Neuroimaging. 2011;21:79–82. https://doi.org/10.1111/j.1552-6569.2009.00381.x . Kastirr I, Kamusella P, Andresen R. Bilateral painful ophthalmoplegia: A case of assumed tolosa-hunt syndrome. J Clin Diagn Res. 2016;10:16–7. https://doi.org/10.7860/JCDR/2016/16703.7496 . Shindler KS, Tolosa-Hunt. syndrome, 2023. https://www.uptodate.com/contents/5248/printwww.uptodate.com . Bae JH, Park CS. Study on the Latency of Blink Reflex. J Korean Acad Rehab Med. 1989;13:71–5. Świątkowska-Stodulska R, Stodulski D, Babińska A, Piskunowicz M, Sworczak K. Bilateral Tolosa-Hunt syndrome mimicking pituitary adenoma. Endocrine. 2017;58:582–6. https://doi.org/10.1007/s12020-017-1422-2 . Fernández S, Godino O, Martínez-Yélamos S, Mesa E, Arruga J, Ramón JM, Acebes JJ, Rubio F. Cavernous sinus syndrome: A series of 126 patients. Medicine. 2007;86:278–81. https://doi.org/10.1097/MD.0b013e318156c67f . Supplementary Files CAREchecklistEnglish2013THS.pdf Cite Share Download PDF Status: Published Journal Publication published 12 Nov, 2024 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Reviewers agreed at journal 05 Oct, 2024 Reviewers invited by journal 15 May, 2024 Editor assigned by journal 28 Apr, 2024 First submitted to journal 27 Apr, 2024 Editorial decision: Minor revisions 25 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4264469","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":302884332,"identity":"b92cfb57-db39-4bd9-bc90-8d37d9a643a7","order_by":0,"name":"Mario Jr Bugay Prado","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDACCRDBxiDHwA4XSmBgYGwgrMWYgZlULYkNRGvRnd177MOPMpv0/mYe0w2MbXcY+NlzDJgLd+DWYnbnXPLMnnNpuTMO85jdYGx7xiDZ88aAeeYZPFpu5Bgz8LYdzm2AaDnMYHADaAtvG34tjH/bDqfLw7TYE6MFqOBwggHcFglCWoB+YZY5l2a48TBb2Y2Ec894JM48Kzg8E5+W272HGd+U2cjLHW/eduND2R05/vbkjY8L8WhhYOBBYicwHABzD+PTgKqFgeEAmGTGom4UjIJRMApGLgAAYehSsZ/nLtwAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-5756-7321","institution":"University of the Philippines Manila","correspondingAuthor":true,"prefix":"","firstName":"Mario","middleName":"Jr Bugay","lastName":"Pr","suffix":"Jr"},{"id":302884333,"identity":"877a3dc4-b170-48b5-9f7e-f38d83ecdfb2","order_by":1,"name":"Angela Apostol-Alday","email":"","orcid":"","institution":"Central Luzon Doctors' Hospital","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"","lastName":"Apostol-Alday","suffix":""},{"id":302884334,"identity":"48457045-9b08-40e9-8187-8ad1c25ce8ac","order_by":2,"name":"Karen Joy Adiao","email":"","orcid":"","institution":"ManilaMed: Medical Center Manila Inc","correspondingAuthor":false,"prefix":"","firstName":"Karen","middleName":"Joy","lastName":"Adiao","suffix":""}],"badges":[],"createdAt":"2024-04-14 09:57:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4264469/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4264469/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-024-01747-6","type":"published","date":"2024-11-12T15:57:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":57444558,"identity":"b148a1a4-e0cf-44d8-9940-d5b7c4d4a68a","added_by":"auto","created_at":"2024-05-30 18:57:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":978165,"visible":true,"origin":"","legend":"\u003cp\u003eNon-contrast (A) and contrast enhanced (B) cranial CT scan. Notice the granulation tissue on the right parasellar area (red arrow on A) which markedly enhanced when contrast was given (red arrow on B).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4264469/v1/fdd5492f6477757f2d99b6b2.png"},{"id":69274849,"identity":"1c76c55b-6aab-4878-954c-77510ec29b66","added_by":"auto","created_at":"2024-11-18 16:34:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1153041,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4264469/v1/b5789ce8-492d-4fd1-9d4d-9856acbc3a25.pdf"},{"id":57442981,"identity":"8b9dd9b4-ae45-403e-9b82-63fe017ac9cf","added_by":"auto","created_at":"2024-05-30 18:49:18","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":1250371,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013THS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4264469/v1/1a35cca728913f9d48075171.pdf"}],"financialInterests":"","formattedTitle":"Bilateral severe Tolosa-Hunt syndrome in an elderly Filipino female: A case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTolosa-Hunt syndrome consists of unilateral orbital or periorbital pain followed within 2 weeks by neuropathy of one of the cranial nerves (CN) in the anterior cavernous sinus, superior orbital fissure or orbital apex, often leading to ophthalmoplegia.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Although the cause remains unknown, it is thought to be induced by granulomatous inflammation or hypertrophic pachymeningitis of the dura surrounding the cavernous sinus.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] In the International Classification of Headache Disorders (ICHD) 3 beta, evidence of this inflammation, either through histology or imaging is required to definitively diagnose THS.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOnly 1\u0026ndash;2 per 1,000,000 individuals are diagnosed with THS.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] While most will present with unilateral symptoms, 4.6% have bilateral involvement, often affecting cranial nerves III, IV and VI incompletely.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Only 2 published cases with simultaneous and complete ophthalmoplegia and ptosis, both resolved either spontaneously or with high dose steroids.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] This paper highlights a THS case with bilateral complete cavernous sinus syndrome initially on the right, followed several months later on the left after intake of low to moderate dose of steroids.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eThe patient was a 78-year-old female, who was admitted for 1 week history of progressively worsening lancinating pain on the right frontal and periorbital area associated with severe dizziness, doubling of vision and drooping of the right eyelid. The past medical, psychosocial and family medical histories were unremarkable. On neurological examination, she was noted to have impaired direct and consensual pupillary eye reflexes, with complete limitation of extra-ocular muscle movement in all directions on the right eye, and hyperesthesia on V1 and V2 areas on the right side of the face. The rest of the neurological and physical examination was unremarkable. Initial plain cranial CT scan, and subsequent cranial MRI with MRA did not show subarachnoid hemorrhage and aneurysm in the circle of Willis or in the cavernous sinuses. However, a repeat cranial CT with contrast done a week later showed enhancement of the right parasellar region on the cavernous sinus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) suggestive of Tolosa-Hunt Syndrome. The patient was started on 20mg per day of prednisone which was titrated gradually, as well as gabapentinoids and opioids for the pain. She was subsequently discharged. During follow up, there was minimal improvement of symptoms.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree months later, the patient was re-admitted due to occurrence of, now, severe left frontal and periorbital pain and vomiting. On neurological examination, she was noted to have bilateral abnormal pupillary light reflexes, complete ophthalmoplegia and hyperesthesia on V1 and V2. The rest of examination was unremarkable. A repeat plain cranial CT scan showed normal findings. A blink reflex was done and revealed prolongation of bilateral R1, R2 and contralateral R2 responses, indicating involvement of bilateral V1 portion of cranial nerve V (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Erythrocyte sedimentation rate (ESR) (37 mm/hr, female nv: \u0026lt;20mm/hr) and C-reactive protein (CRP) (3.81 mg/dl, high risk value: \u0026gt;3.0 mg/dl) were slightly elevated. Complete blood count, electrolytes, thyroid function test, repetitive nerve stimulation, creatine kinase MM and total, chest x-ray, electrocardiogram and 2D echo were all normal. A cerebral venogram was done and revealed no occlusion of the bilateral cavernous sinus nor evidence of enlarging pituitary mass. A diagnosis of bilateral idiopathic THS was made. Thus, prednisone was immediately increased to 60mg/day. She was subsequently discharged a week later. On follow up, the dizziness and headache significantly improved. There was mild improvement on bilateral upward gaze, but minimal on the rest of the extraocular muscles.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBlink reflex showing prolonged bilateral R1, R2 and contralateral R2 latencies.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStimulation Site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eR1 latency (nv:\u0026lt;9.78ms)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR2 latency (nv: \u0026lt;26.8ms)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eR2\u0026rsquo; Latency (nv\u0026thinsp;\u0026lt;\u0026thinsp;27.2 ms)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e34.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe occurrence of retroorbital pain followed by complete ophthalmoplegia, in the presence of granulomatous inflammation on the ipsilateral cavernous sinus detected using imaging study and in the absence of other underlying conditions, is sufficient to confirm the diagnosis of THS.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Previous diagnostic criteria of International Headache Society (IHS) used to include response to steroids be present. However, this was revised in ICHD3 beta, as steroids was only found to relieve pain but not ophthalmoplegia in most patients.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn theory, it seems expected that the granulation tissue on the cavernous sinus may extend to the ipsilateral superior orbital fissure, orbital apex, sphenoid sinus and middle cranial fossa. On the contrary, there are only few cases reporting complete involvement of the contralateral side.[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Swiatkowska reported a case of isolated right abducens nerve palsy preceded by retroorbital headache for which the diagnosis of \u0026ldquo;bilateral\u0026rdquo; THS was made after the patient was found to have granulomatous inflammation on both cavernous sinuses on imagine.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Kastir and Sugie each reported simultaneous occurrence of THS on both sides which were responsive to high dose steroid and supported by imaging.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In addition to abnormal enhancement of the granulation tissue, Sugie suspected that idiopathic hypertrophic pachymeningitis (IHP) on both sides may have compressed and induced ischemia of the cranial nerves on the cavernous sinuses, and that THS and IHP share similar pathological features.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Although our case also ended up with bilateral THS, the delayed occurrence of the condition on the left side for about 3 months while on steroid was peculiar. We suspect that the initiation of low to moderate dose of steroid during the initial THS may have reduced the rate of progression of inflammation to the contralateral side.\u003c/p\u003e \u003cp\u003eThe incidence of THS is 1\u0026ndash;2 cases per million individuals, but only 4% will manifest with bilateral and usually incomplete affection of cranial nerves housed in the cavernous sinuses.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] While the cases of Sugie and Kastir manifested with complete ophthalmoplegia, there was no mention of bilateral CN V1 and V2 involvement.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In classic complete cavernous sinus syndrome, CN III, IV, V1 and V2 embedded in the dura located on the lateral aspect, CN VI near the internal carotid artery (ICA), are all affected. Occasionally, parasympathetic and sympathetic outputs intertwined with CN III and ICA, respectively are also damaged leading to impaired pupillary reflexes.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Thus, aside from being bilaterally affected, our case further demonstrated severe and a complete syndrome making the localization straightforward. Localizing and identifying the syndrome of multiple CN deficits is important as this will narrow down differential diagnosis.\u003c/p\u003e \u003cp\u003eThe absence of immediate response to steroids in our case may make the THS diagnosis questionable. Accordingly, in ICHD 1 and 2 diagnostic criteria for THS, pain and cranial nerve palsies should resolve within 72 hours after steroid initiation.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] However, this latter criterion was removed in the latest guideline as cranial nerve palsies was found to take longer time to improve. Furthermore, response to any drug should not be the basis for diagnosis as several entities such as such as sarcoidosis and lymphoma also present similarly as THS and likewise respond to steroid. In addition, the type, duration and optimal dose of steroid has not been established yet in any large studies.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] In our report, the initial steroid dose did not alleviate the pain on the right frontal and periorbital areas, nevertheless, we hypothesize that it could have protracted the involvement of the left. The administration of high dose steroid eventually alleviated the pain; thus, we recommend that pulse therapy or high oral dose (1mg/kg) of steroid be immediately initiated in any case of THS if there are no contraindications.\u003c/p\u003e \u003cp\u003eIn conclusion, THS should be considered in patients presenting with bilateral painful ophthalmoplegia whether simultaneously or in succession. Pulse therapy or high dose oral steroid is recommended as initial treatment for THS unless there are contraindications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTolosa-Hunt Syndrome (THS)\u003c/p\u003e\n\u003cp\u003eCranial nerves (CN)\u003c/p\u003e\n\u003cp\u003eInternational Classification of Headache Disorders (ICHD)\u003c/p\u003e\n\u003cp\u003eErythrocyte sedimentation rate (ESR)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eC-reactive protein (CRP)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInternational Headache Society (IHS)\u003c/p\u003e\n\u003cp\u003eInternal carotid artery (ICA)\u003c/p\u003e"},{"header":"Declarations","content":"\u003col\u003e\n \u003cli\u003eFunding: Not applicable\u003c/li\u003e\n \u003cli\u003eConflict of Interest: The authors declare no conflict of interest\u003c/li\u003e\n \u003cli\u003eEthics approval: Ethics approval was waived for this report.\u003c/li\u003e\n \u003cli\u003eConsent to participate: Written consent to participate was obtained from the patient.\u003c/li\u003e\n \u003cli\u003eWritten consent for publication: Written consent for publication was obtained from the patient.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAvailability of data and material: Not applicable\u003c/li\u003e\n \u003cli\u003eCode availability: Not applicable\u003c/li\u003e\n \u003cli\u003eAuthor Contributions: Conceptualization: MP, AAA Data Curation: MP Investigation: MP, AAA and KA, Original Draft: MP, AAA and KA, Review and Editing: MP, AAA and KA.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDutta P, Anand K. Tolosa-Hunt syndrome: A review of diagnostic criteria and unresolved issues. J Curr Ophthalmol. 2021;33:104\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4103/joco.joco_134_20\u003c/span\u003e\u003cspan address=\"10.4103/joco.joco_134_20\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSugie K, Morikawa M, Taoka T, Hirano M, Ueno S. Serial neuroimaging in tolosa-hunt syndrome with acute bilateral complete ophthalmoplegia. J Neuroimaging. 2011;21:79\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1552-6569.2009.00381.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1552-6569.2009.00381.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKastirr I, Kamusella P, Andresen R. Bilateral painful ophthalmoplegia: A case of assumed tolosa-hunt syndrome. J Clin Diagn Res. 2016;10:16\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7860/JCDR/2016/16703.7496\u003c/span\u003e\u003cspan address=\"10.7860/JCDR/2016/16703.7496\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShindler KS, Tolosa-Hunt. syndrome, 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.uptodate.com/contents/5248/printwww.uptodate.com\u003c/span\u003e\u003cspan address=\"https://www.uptodate.com/contents/5248/printwww.uptodate.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBae JH, Park CS. Study on the Latency of Blink Reflex. J Korean Acad Rehab Med. 1989;13:71\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eŚwiątkowska-Stodulska R, Stodulski D, Babińska A, Piskunowicz M, Sworczak K. Bilateral Tolosa-Hunt syndrome mimicking pituitary adenoma. Endocrine. 2017;58:582\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12020-017-1422-2\u003c/span\u003e\u003cspan address=\"10.1007/s12020-017-1422-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFern\u0026aacute;ndez S, Godino O, Mart\u0026iacute;nez-Y\u0026eacute;lamos S, Mesa E, Arruga J, Ram\u0026oacute;n JM, Acebes JJ, Rubio F. Cavernous sinus syndrome: A series of 126 patients. Medicine. 2007;86:278\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/MD.0b013e318156c67f\u003c/span\u003e\u003cspan address=\"10.1097/MD.0b013e318156c67f\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Bilateral Tolosa Hunt Syndrome, Cavernous Sinus Syndrome, Painful Ophthalmoplegia","lastPublishedDoi":"10.21203/rs.3.rs-4264469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4264469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOnly 1\u0026ndash;2 per 1,000,000 individuals are diagnosed with Tolosa Hunt Syndrome (THS). While most will present with unilateral symptoms, 4.6% have bilateral involvement, often affecting cranial nerves III, IV and VI incompletely.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Only 2 papers published cases with simultaneous and complete ophthalmoplegia and ptosis, both resolved either spontaneously or with high dose steroids. This case highlights a THS case with bilateral complete cavernous sinus syndrome initially on the right, followed several months later on the left.\u003c/p\u003e\u003ch2\u003eCase Report:\u003c/h2\u003e \u003cp\u003eHere we report a 78 years old female who was diagnosed with right sided then followed 3 months later by left sided THS while on low to moderate dose of steroids. She had bilateral painful ophthalmoplegia, hyperesthesia on the ophthalmic and maxillary branches of cranial nerve V and absent direct and consensual pupillary eye reflexes. She had prolonged bilateral R1, R2 and R2\u0026rsquo; on blink reflex confirming affection of CN V, and enhancement on the right parasellar area on contrast-enhanced cranial CT indicating presence of granulation tissue.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTHS should be considered in a patient presenting with bilateral painful ophthalmoplegia whether this happens simultaneously or in succession. Pulse therapy or high dose oral steroid is recommended as initial treatment for THS unless there are contraindications.\u003c/p\u003e","manuscriptTitle":"Bilateral severe Tolosa-Hunt syndrome in an elderly Filipino female: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-30 18:49:13","doi":"10.21203/rs.3.rs-4264469/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-10-05T16:36:16+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-15T15:37:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-29T00:47:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2024-04-27T04:42:26+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revisions","date":"2024-04-25T08:56:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f98ca364-62ca-4a33-8283-8ee7fca127b6","owner":[],"postedDate":"May 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-18T15:59:56+00:00","versionOfRecord":{"articleIdentity":"rs-4264469","link":"https://doi.org/10.1007/s42399-024-01747-6","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2024-11-12 15:57:05","publishedOnDateReadable":"November 12th, 2024"},"versionCreatedAt":"2024-05-30 18:49:13","video":"","vorDoi":"10.1007/s42399-024-01747-6","vorDoiUrl":"https://doi.org/10.1007/s42399-024-01747-6","workflowStages":[]},"version":"v1","identity":"rs-4264469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4264469","identity":"rs-4264469","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}