Sinonasal Aspergillosis Complicated with Cavernous Sinus Syndrome 座長、各位師長前輩大家好，接下來由馬偕醫院報告關於Cavernous sinus syndrome complicated with Sinonasal Aspergillosis 的一個案例 蔡以璿1 陳柏年1 2 黃佩雯3 台北馬偕紀念醫院 1耳鼻喉科 新竹馬偕紀念醫院 2耳鼻喉科 3病理科 1

Brief History 76-year old female Chief complaint : Past history : binocular diplopia and blurred vision for 8 days numbness and pain of Lt upper face Past history : rectal adenocarcinoma, cT2N1aM0, stage IIIa, s/p CCRT DM, HTN, hepatitis B, peptic ulcer 病患是一位76歲女性 主訴是入院前8天，出現雙眼複視及視力模糊的情形並伴隨有雙側 回顧過去病史，他有 DM、HTN等內科疾病 並且4個月前因為rectal cancer 接受過CCRT

Clinical course rectal adenocarcinoma, cT2N1aM0, stage IIIa s/p RT (50Gy,25fr) (2017/11-2018/02) /p UFUR (2018/11 ~ ) ER and neurological ward : - Binocular diplopia and blurred vision for 8 Ds Numbness and pain of Lt upper face Left abducens palsy 2017/11-2018/02 2018/06 Post OP condition: Improved EOM and facial numbness Discharge (2018/07/12) ENT: Biopsy and sinus CT Pathology: chronic inflammation 因為雙眼複視及視力模糊情形至新竹馬偕急診，會診神經內科發現左眼無法向外看，懷疑有神經內科疾病，之後收進神經內科進一步檢查 因此會診我們耳鼻喉科 7/02安排左側鼻竇內視鏡手術 術後病人EOM及臉麻恢復良好於術後第10天出院 Operation: Lt ESS 2018/06 2018/07/02 2018/07

Admission in neurology ward Abducens palsy of left eye Admission in neurology ward Lt CN VI palsy Fundoscopy : optic discs and retinal vessels were normal Visual field examination : normal visual field in both eyes Blood exam, cultures and lumbar puncture exam: negative findings 於神經內科病房，NE發現左側外旋神經麻痺 眼底鏡、視野檢查無異常 其他抽血(包括血液、生化及免疫檢查無顯著異常)、血液培養及腰椎穿刺無特殊表現 治療方面先使用可過BBB的抗生素ceftriaxone 和類固醇Dexamethaxone

MRI of Brain Contrast enhanced lesion in Lt cavernous sinus 安排Brain MRI 發現左側cavernous sinus有contrast enhanced lesion，左側鼻竇有發炎情形 BACK Contrast enhanced lesion in Lt cavernous sinus (from apex to post wall)

Nasal polyps in from Lt middle meatus and OMC Sinuscopy findings: 鼻竇內視鏡下發現 左側中鼻道OMC 有polypod lesion biopsy 結果是papilloma like lesion 沒有看到明顯的 eschar 或 hyphae Nasal polyps in from Lt middle meatus and OMC

Paranasal sinus CT: 5 A 5 B 5 C 安排電腦斷層發現，左側pansinusitis，並且有calcification, 是fungal sinusitis, typical 表現

Tentative diagnosis and plan #. Cavernous sinus syndrome with Lt CN V(1+2) and VI involvement #. Lt chronic rhinosinusitis, highly suspected fungal infection 因此病人診斷是 Cavernous sinus syndrome involved到左側 CN 5-1, 5-2 和CN 6 疑似黴菌感染所造成的 Lt pansinusitis BACK

Operation (2018/07/02): Lt ESS 術中發現左側OMC內有明顯的Fungus ball，接下來一一把左側所有的鼻竇打開

Pathology PAS 400 x GMS 400 x BACK PAS and GMS 染色可以發現具Aspergillus 特色的fungal hyphae (菌絲比起mucomycosis菌絲要粗，而且角度呈現銳角。) BACK

Post OP condition Pre OP Post OP day 7 術後第三天，Lt abducent palsy 恢復 7-8成

Final diagnosis and plan #. Cavernous sinus syndrome with Lt CN V(1+2) and VI involvement #. Lt sinunasal Aspergillosis /p Lt ESS on 2018/07/02 因此最後診斷為 Cavernous sinus syndrome involved到左側 CN 5-1, 5-2 和CN 6 及 左側aspergillosis related CRS

Discussion: What is cavernous sinus ? venous plexus that lies between the periosteal and dural layers of the dura mater central base of the skull, on either side of the sella turcica Content: internal carotid artery (ICA), CN III, CNV1, V2, CNVI, sympathetic plexus 接下來進入到討論的部分，什麼是cavernous sinus (中文叫海綿竇):海綿竇是一個靜脈叢，位於skull base 的 dura layer以及periosteal layer 之間，左右海綿竇中間夾著sella 海綿竇中間有一些重要的解剖構造: internal carotid artery，第3、5-1、5-2及第6及部分交感神經叢

Cavernous sinus 1: hypophysis, 2: internal carotid artery, 3: CN VI 4: meningeal (outer) layer, 5: cavernous sinus, 6: sphenoid sinus, 7: endosteal (inner) layer, 8: CN V1 9: CN V2 10: CN IV 11: CN III 12: the outer layer at the diaphragma sellae 這張圖說明海棉竇中 那些重要構造的解剖相對位置 sphenois sinus 在這裡 CN3 4 V1 V2 ICA 6 Case Rep Surg. 2016; 2016: 6458189

What is cavernous sinus syndrome? Signs and symptoms resulting from the compromise of the 2 or more structure passing through the CS CN III (Proptosis) (Ophthalmoplegia) CN IV (vertical diplopia) CN VI (abducens palsy) CN V1, V2 (upper face numbness) Oculosympathetic fibers (Horner’s syndrome) 什麼是cavernous sinus syndrome ? 要涵蓋兩個或以上 cavernous sinus 中的構造 受到影響而產生的症狀 第三對 有Proptosis, Ophthalmoplegia 第四對有vertical diplopia 第六對有 外展麻痺 第五對 有上半臉感覺異常 交感神經有Horner yndrome 等 Etiology 可大致分成 腫瘤性 血管性 感染性 間質發炎性 （Tolosa Hunt syndrome） 以及其他等 Cavernous Sinus Syndrome Analysis of 151 Cases. Arch  Neurol. 1996;53:967-971 Etiology: neoplastic, vascular, infectious and miscellaneous inflammatory disorders (Tolosa Hunt syndrome), others Cavernous sinus syndrome: A prospective study of 73 cases at a tertiary care centre in Northern India, Clinical Neurology and Neurosurgery 155 (2017) 63–69

Etiology of CSS 西班牙 Barcelona 一篇 126 cases study 指出 neoplastic 佔大宗 80 個 case 63% 而 Aspergillosis 只有一個 case Cavernous Sinus Syndrome, A Series of 126 Patients, Medicine 2007;86:278–281

北印度一篇 73 cases retrospectic study指出 neoplastic, fungal infection, 及 Tolosa Hunt 相差無幾 Cavernous sinus syndrome: A prospective study of 73 cases at a tertiary care centre in Northern India, Clinical Neurology and Neurosurgery 155 (2017) 63–69

Diagnosis Cavernous sinus syndrome on MRI: Contrast enhanced lesion in CS Fungal sinusitis on CT-scan: Unilateral sinus hypodense mass Calcifications within the lesion Biopsy for the nose and paranasal lesion 診斷的部分 Cavernous sinus syndrome 依照 主要是 臨床 加上 MRI 診斷 MRI 上要有Cavernous sinus contrast enhanced lesion 而Fungal sinusitis induced CSS 則除了要有CSS的表現 在CT 上 還可以看到單側鼻竇 hypodense lesion 並其中有一些鈣化

Treatment for CSS complicated by SNA Surgical intervention with ESS Medication: Antibiotics cross BBB (ex: Ceftriaxone and vancomycin) for 2nd CNS bacterial infection Antifungal therapy Steroids cross BBB (ex: dexamethasone), controversial 治療方面  以鼻竇內視鏡手術去清除病灶  藥物以可以通過BBB 的抗生素 、類固醇加上 anti fungal treatment 我們的case 未使用 anti fungal agent 是因為術後恢復狀況良好，且pathogen 為Aspergillosis 是一種fungi-induced allergic sinusitis 顧考慮病人 underlying disease (DM, HTN, Liver function) 與抗黴菌藥的毒性，故未使用抗黴菌藥物

Conclusion and take home massage The anatomy of cavernous sinus and the definition of cavernous sinus syndrome The etiology of CSS and fungal sinusitis SNA: non invasive fungi-induced allergic sinusitis, it can still cause severe complications (such as CSS), esp in the immunocompromised patient The treatment for this case included timely ESS , prophylactic antibiotics and steroid. 結論 暸解 cavernous sinus anatomy 並知道如何去診斷 CSS SS的etiology 不要忘了和我們耳鼻喉科 相關的 fungal sinusitis SNA一般被認為是non invasive sinusitis 但仍有可能會引起較嚴重的complication, 如本例的CSS，特別是在immunocompremise patient (如本例接受過 CCRT，有DM)，及時手術可恢復良好

Thanks for your attention!!

Reference [1] Jaime Toro, Lisseth Estefania Burbano, Saúl Reyes, Paula Barreras Cavernous sinus syndrome: need for early diagnosis, BMJ Case Rep 2015. doi:10.1136 [2] Susana Ferna´ndez, MD, Oscar Godino, MD, Sergio Martı´nez-Ye´lamos, MD, Edilia Mesa, MD, Jordi Arruga, PhD, Jose´ Marı´a Ramo´n, MD, Juan Jose´ Acebes, MD, and Francisco Rubio, MD Cavernous Sinus Syndrome, A Series of 126 Patients, Medicine 2007;86:278–281 [3] S. Bhatkar, M.K. Goyal, A. Takkar, K.K. Mukherjee, P. Singh, R. Singh, V. Lal, Cavernous sinus syndrome: A prospective study of 73 cases at a tertiary care centre in Northern India, Clinical Neurology and Neurosurgery 155 (2017) 63–69 [4] Bhatkar S1, Goyal MK1, Takkar A1, Modi M1, Mukherjee KK2, Singh P3, Radotra BD4, Singh R5, Lal V1.J Neurosci Rural Pract. 2016 Dec;7(Suppl 1):S68-S71. doi: 10.4103/0976-3147.196448. [5] Chi TH, Chen HS, Yuan CH, Su FM. J Coll Acute fulminant invasive fungal sinusitis with cavernous sinus syndrome. Physicians Surg Pak. 2014 Nov;24 Suppl 3:S240-2. doi: 11.2014 [6] Haegelen C, Godey B, Riffaud L, Le Gall F, Sinus cavernous syndrome caused by isolated aspergillosis of the sphenoid sinus Rev Neurol (Paris). 2003 Feb;159(2):209-11 [7] James R. Keane, MD. Cavernous Sinus Syndrome Analysis of 151 Cases. Arch Neurol. 1996;53:967- 971

Post OP 2 month 術後兩個月的內視鏡檢查可以看到傷口復原的很好 Ethomoid sinus Sphenoid sinus

The classification of CSS Jefferson 1938 年 提出將CSS 依照 三叉神經不同分支的影響情形以及是否出現動眼麻痺 而分成 前中後 三類 Ishikawa 1996 年 提出將CSS 依照 lesion解剖位置的不同，分成 前 從orbital apex 至orbital apex 後 3.5mm， 中 orbital apex後 3.5mm到orbital apex 後 10mm, 後 orbital apex 後 10mm 到 cavernous sinus posterior wall

The difference was not statistically significant 一篇北印度paper 將 他們 73 個 CSS按照 這兩種分類方法 發現 以 Ishikawa 分類下去 anterior CSS 以 Tolosa Hunt syndrome 以及 Vascular disease 居多 Posterior 以 Fungal 及 neoplastic disease 居多 所以 CSS etiology 會有地域性 或 國家發展程度 不同 而有差異性 The difference was not statistically significant J Neurosci Rural Pract. 2016 Dec;7(Suppl 1):S68-S71. doi: 10.4103/0976-3147.196448.