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CAVERNOUS SINUS SYNDROMECAVERNOUS SINUS SYNDROME

Denis Jusufbegovic, M.D.Denis Jusufbegovic, M.D.University of LouisvilleUniversity of Louisville

Department of Ophthalmology and Visual SciencesDepartment of Ophthalmology and Visual Sciences

01/04/1301/04/13

SubjectiveSubjectiveCC:CC: “ blurred vision OD x 1 month, double vision x 1-2 “ blurred vision OD x 1 month, double vision x 1-2

wks”wks”

HPIHPI: 34 yo WM was referred to oculoplastics clinic on : 34 yo WM was referred to oculoplastics clinic on 09/25/12 for occasional double vision x 1-2 wks. 09/25/12 for occasional double vision x 1-2 wks.

Pt. also c/o of numbness around his R eye, Pt. also c/o of numbness around his R eye, intermittent headache and episodes of vomiting.intermittent headache and episodes of vomiting.

Patient’s problems started on 08/28/12 after Patient’s problems started on 08/28/12 after being being splashed with power hose at work splashed with power hose at work sustaining blunt sustaining blunt trauma to R eye and face. He trauma to R eye and face. He sought no medical sought no medical attention.attention.

-

He started developing ocular pain, photophobia, facial He started developing ocular pain, photophobia, facial numbness and worsening vision OD few days after his numbness and worsening vision OD few days after his injury. Was seen by local ophthalmologist on 09/07/12:injury. Was seen by local ophthalmologist on 09/07/12:

Exam was significant for: Exam was significant for: BCVA OD 20/200 OS: 20/20BCVA OD 20/200 OS: 20/20

Slightly dilated min reactive pupil OD, no APDSlightly dilated min reactive pupil OD, no APD

Full EOMFull EOM

OD: Eyelid edema, conj. injection, 4+cells/2+flare, OD: Eyelid edema, conj. injection, 4+cells/2+flare, no vitritis, retina flat no vitritis, retina flat

Diagnosed with traumatic iritis, treated with PF q1-2 hDiagnosed with traumatic iritis, treated with PF q1-2 h

3 days follow up by local ophthalmologist on 3 days follow up by local ophthalmologist on 09/10/12 showed:09/10/12 showed:

- improved BCVA OD 20/80 from 20/200- improved BCVA OD 20/80 from 20/200

- OD: 2+cells, 2+flare, mutton-fat KPs- OD: 2+cells, 2+flare, mutton-fat KPs

- no other exam changes- no other exam changes

Diagnosis: Iritis OD Diagnosis: Iritis OD

Tx: Prednisone 80 mg PO to be tapered over Tx: Prednisone 80 mg PO to be tapered over 2 wks2 wks

He returned to local ophthalmologist on He returned to local ophthalmologist on 09/15/12 c/o “eye making popping sounds”09/15/12 c/o “eye making popping sounds”

Significant exam findings:Significant exam findings:

BCVA OD 20/70 OS 20/20BCVA OD 20/70 OS 20/20

No APD, full EOMNo APD, full EOM

“ “sunken eye socket OD”sunken eye socket OD”

AC was deep and quiet ODAC was deep and quiet OD

Plan: complete PO Prednisone taper and obtain Plan: complete PO Prednisone taper and obtain CT orbitsCT orbits

11stst oculoplastics visit oculoplastics visitHPIHPI: Pt. c/o intermittent binocular diplopia x 1-: Pt. c/o intermittent binocular diplopia x 1-2 wks, photophobia OD, daily headaches assoc. 2 wks, photophobia OD, daily headaches assoc. with nausea/vomiting, numbness and tingling with nausea/vomiting, numbness and tingling around R eyearound R eye

POH: unremarkable except recent injury: unremarkable except recent injury

PMH: negative: negative

FHFH: non-contributory : non-contributory AllAll: : NKDA

MEDS: PredForte OD QID ROS: negative

ObjectiveObjective

20/20

20/25 P

4 2

3 2O RAPD, brisk

OU

T12

13

BCVA

EOM: inconsistent mild -1 adduction deficit OD

Hertel:

10010

12

External: partial numbness R V1 and

V2, intact V3

ObjectiveObjectiveSLESLE:: ODOD OSOS

L/LL/L normal OU normal OU

C/SC/S clear OU clear OU

KK clear OU clear OU

ACAC 1+ c/f quiet 1+ c/f quiet

I/LI/L faint pigment clear faint pigment clear

on ant. capsuleon ant. capsule

Vit no cells OUVit no cells OU

DFEDFE: unremarkable except inf. temp PVD OD: unremarkable except inf. temp PVD OD

Imaging Imaging

Single coronal CT face image demonstrates questionable small R orbital floor fracture and extensive pneumatization of sinuses of unknown significance

Impression and PlanImpression and Plan

Resolving iritis OD, no obvious Resolving iritis OD, no obvious orbital fxs orbital fxs

Observation, RTC in 2-3 weeks. Observation, RTC in 2-3 weeks. Repeat CT scan if symptoms Repeat CT scan if symptoms persist persist

Follow up on 10/02/12Follow up on 10/02/12Pt. returned to clinic in 1 week c/o worsening Pt. returned to clinic in 1 week c/o worsening diplopia, headaches, episodes of vomiting and facial diplopia, headaches, episodes of vomiting and facial numbness. He reported his R eye was “stuck”. No numbness. He reported his R eye was “stuck”. No other complaints such as fever, chills, night sweats.other complaints such as fever, chills, night sweats.

ExternalExternal: pronounced decreased sensation R V1 : pronounced decreased sensation R V1 and V2and V2

and RUL ptosis with decreased LF of 4mmand RUL ptosis with decreased LF of 4mm

EOMEOM: -3 limitation in all gaze directions OD; full OS: -3 limitation in all gaze directions OD; full OS

SLESLE: unchanged 1+ c/f: unchanged 1+ c/f

BCVA20/50

P5 NR

3 2, brisk

No RAPD

Impression Impression

Rapidly progressive R cranial nerve III, IV, V Rapidly progressive R cranial nerve III, IV, V and VI palsy consistent with cavernous sinus and VI palsy consistent with cavernous sinus process process

DDx: DDx: Inflammatory Inflammatory ( orbital pseudotumor, Talosa-Hunt syndrome, ( orbital pseudotumor, Talosa-Hunt syndrome,

sarcoid, etc)sarcoid, etc)

Vascular Vascular (c-c fistula, cavernous sinus thrombosis)(c-c fistula, cavernous sinus thrombosis)

Neoplastic Neoplastic ( infiltration by hematologic or solid malignancies)( infiltration by hematologic or solid malignancies)

Infectious Infectious (bacterial, fungal)(bacterial, fungal)

PlanPlan

Urgent hospital admissionUrgent hospital admission

MRI brain and orbits with gadolinium; MRI brain and orbits with gadolinium; MRA/MRVMRA/MRV

CXRCXR

Lab work:, CBC, CMP, ESR, CRP, ACE, c-Lab work:, CBC, CMP, ESR, CRP, ACE, c-ANCA, p-ANCA, RPR, quantiFERON-TBANCA, p-ANCA, RPR, quantiFERON-TB

ResultsResults

MRA/MRV: no C-C fistula, no MRA/MRV: no C-C fistula, no aneurysmaneurysm

CXR: no hilar lymphadenopathyCXR: no hilar lymphadenopathy

Lab work: negative Lab work: negative

MRIMRI

Coronal T1 MRI orbital/brain post contrast images show enhancement of R orbital soft tissue extending toward orbital apex, extensive pneumatization of sinuses and bilateral maxillary sinus disease

MRI MRI

Axial T1 MRI orbital/brain post contrast images demonstrate R orbital soft tissue enhancement extending through orbital apex/superior orbital fissure to cavernous sinus. Soft tissue fullness R cavernous sinus, streaky enhancement of retrobulbar fat of both orbits R>L

Impression/PlanImpression/Plan

Idiopathic inflammation possible Idiopathic inflammation possible Talosa-Hunt syndromeTalosa-Hunt syndrome

IV corticosteroidsIV corticosteroids

Discharged home on 2Discharged home on 2ndnd hospital hospital day on Prednisone PO 80 mg dailyday on Prednisone PO 80 mg daily

Follow up on 10/09/12Follow up on 10/09/12

Pt. continues to c/o binocular horizontal/vertical Pt. continues to c/o binocular horizontal/vertical diplopia and headaches. diplopia and headaches.

BCVABCVA OD 20/100 OS 20/20 OD 20/100 OS 20/20

PupilsPupils: OD 5mm NR, OS 3mm reactive, no : OD 5mm NR, OS 3mm reactive, no RAPDRAPD

ExternalExternal: slightly improved R V1 and V2 : slightly improved R V1 and V2 sensation,sensation,

improved ptosis OD improved ptosis OD

EOMEOM: slightly improved motility: slightly improved motility

SLESLE: +0.5 cells/flare OD: +0.5 cells/flare OD

Image montage of five gaze positions demonstrates mild RUL ptosis and -2 limitation of extraocular motility in all gaze directions

Impression/PlanImpression/Plan

Mild improvement of R cavernous Mild improvement of R cavernous sinus syndrome on high dose sinus syndrome on high dose corticosteroidscorticosteroids

Clinical presentation concerning for R Clinical presentation concerning for R cavernous sinus carcinomatosiscavernous sinus carcinomatosis

Corticosteroid taper, neuro-ophth and Corticosteroid taper, neuro-ophth and neurosurgery consult neurosurgery consult

Neuro-ophth evaluationNeuro-ophth evaluation Pt. was seen in neuro-ophthalmology Pt. was seen in neuro-ophthalmology

clinic within one week. He reported no clinic within one week. He reported no improvements in his symptoms improvements in his symptoms

Corticosteroids were slowly taperedCorticosteroids were slowly tapered

Given response to corticosteroids and Given response to corticosteroids and lesion location, biopsy was postponed lesion location, biopsy was postponed at this timeat this time

Over the next four weeks pt. reported Over the next four weeks pt. reported slight improvement in his diplopia. slight improvement in his diplopia.

However, he c/o headache, nausea, However, he c/o headache, nausea, occasional vomiting, loss of appetite, occasional vomiting, loss of appetite, 15 lbs. weight loss x 3 weeks15 lbs. weight loss x 3 weeks

Turn for the worseTurn for the worse Pt. presented to ER on 11/24/12 with dyspnea at Pt. presented to ER on 11/24/12 with dyspnea at

rest, body aches, dry cough, fevers x 1 weekrest, body aches, dry cough, fevers x 1 week

CBC showed pancytopenia: wbc 1.97, Hgb 8.6, plts CBC showed pancytopenia: wbc 1.97, Hgb 8.6, plts 12K12K

CT chest showed diffuse ground glass opacities and CT chest showed diffuse ground glass opacities and left pleural effusionleft pleural effusion

Pt. was admitted and started on broad spectrum Pt. was admitted and started on broad spectrum abx, underwent thoracentesis with 1L bloody abx, underwent thoracentesis with 1L bloody exudate and bone marrow biopsy exudate and bone marrow biopsy

Hospital CourseHospital Course

Pt. continued to worsen and was Pt. continued to worsen and was transferred to ICU for acute transferred to ICU for acute respiratory distress syndrome respiratory distress syndrome (ARDS) and multi system failure(ARDS) and multi system failure

He expired in early December 2012He expired in early December 2012

Final DiagnosisFinal Diagnosis

Thoracentesis fluid flow cytometry analysis Thoracentesis fluid flow cytometry analysis showed monoclonal showed monoclonal CD3-/CD4-/CD8-/CD16-/CD 56+ lymphocytesCD3-/CD4-/CD8-/CD16-/CD 56+ lymphocytes

Bone marrow biopsy confirmed the same Bone marrow biopsy confirmed the same resultsresults

These findings are consistent with: These findings are consistent with:

Natural killer T cell lymphoma Natural killer T cell lymphoma

DiscussionDiscussionLymphoma of the Ocular Lymphoma of the Ocular

AdnexaAdnexa 1%-2% of all lymphomas and 8% of 1%-2% of all lymphomas and 8% of

extranodal lymphomas arise in the extranodal lymphomas arise in the ocular adnexa ocular adnexa

10%-20% of orbital mass lesions are 10%-20% of orbital mass lesions are found to be lymphoid tumorsfound to be lymphoid tumors

Lymphomas are the most common Lymphomas are the most common orbital malignancy orbital malignancy

Ferry JA, Fung CY, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb;31(2):170-84.

Lymphoma of the Ocular Lymphoma of the Ocular AdnexaAdnexa

Most lymphomas arising in the Most lymphomas arising in the ocular adnexa are low-grade B-cell ocular adnexa are low-grade B-cell lymphomaslymphomas

SYSTEMIC OCULAR ADNEXAL LYMPHOMA (OAL),n=353

Diffuse large B-cell 30.6%

MALT 52%

Follicular 22.1%

Follicular 23%

MALT 7.6%

Diffuse large B-cell 8%

CLL 6.7%

Mantle Cell 5%

Mantle Cell 6.0%

CLL 4%

Ferry JA, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb;31(2):170-84.

Harris NL, et al. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. Hematol J. 2000;1(1):53-66

Natural Killer T (NK/T)-Natural Killer T (NK/T)-cell lymphomacell lymphoma

NK/T-cell lymphoma, known as "lethal midline NK/T-cell lymphoma, known as "lethal midline granuloma“, is a rare disorder in the USgranuloma“, is a rare disorder in the US

Type of extranodal lymphoma most commonly Type of extranodal lymphoma most commonly originating from nasal passages and paranasal sinusesoriginating from nasal passages and paranasal sinuses

More prevalent in Asia and South America where it More prevalent in Asia and South America where it comprises 5% of all non-Hodgkin lymphomas. Avg age comprises 5% of all non-Hodgkin lymphomas. Avg age at presentation is 52 yrsat presentation is 52 yrs

Virtually all cases contain monoclonal episomal EBV Virtually all cases contain monoclonal episomal EBV DNADNA

Kanavaros P, et al. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood. 1993;81(10):2688.Jaffe ES, et al.. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20(1):103.

Ocular complications of Ocular complications of NK/T-cell lymphomaNK/T-cell lymphoma

Primary orbital/ocular NK/T lymphoma is a Primary orbital/ocular NK/T lymphoma is a very rare condition with only 8 cases very rare condition with only 8 cases reported reported

Orbital/ocular involvement is most Orbital/ocular involvement is most commonly an extension of nasal and commonly an extension of nasal and paranasal sinus diseaseparanasal sinus disease

Vision-threatening complications stem Vision-threatening complications stem from orbital inflammation or uveitis/vitritisfrom orbital inflammation or uveitis/vitritis

Ely A, et al. Orbital involvement in extranodal natural killer T cell lymphoma: an atypical

case presentation and review of the literature. Orbit. 2012 Aug;31(4):267-9.

Ocular complicationsOcular complications Hon et al retrospectively studied records of 35 consecutive Hon et al retrospectively studied records of 35 consecutive

patients with NK/T lymphoma between 1996-2000patients with NK/T lymphoma between 1996-2000

24 pts had primary nasal/sinus disease24 pts had primary nasal/sinus disease

6 out of 24 pts (25%) developed ocular complications: 6 out of 24 pts (25%) developed ocular complications:

3 pts had orbital infiltration only 3 pts had orbital infiltration only

1 pts with orbital infiltration and uveitis/vitritis1 pts with orbital infiltration and uveitis/vitritis

2 pt with uveitis/vitritis only2 pt with uveitis/vitritis only

Intraocular involvement such as uveitis and vitritis is an Intraocular involvement such as uveitis and vitritis is an important feature predicting high probability of important feature predicting high probability of leptomeningeal or CNS involvementleptomeningeal or CNS involvement

Hon et al. Vision-threatening Complications of Nasal T/NK Lymphoma. American Journal of Ophthalmology 2002; 134 (3): 407-410.

PrognosisPrognosis

Extranodal NK/T cell lymphoma is a Extranodal NK/T cell lymphoma is a very aggressive diseasevery aggressive disease

Patients with extranasal disease Patients with extranasal disease have median survival of 4 monthshave median survival of 4 months

Thank youThank you

ReferencesReferences1.1.Ely A, Evans J, Sundstrom JM, Malysz J, Specht CS, Wilkinson M. Orbital involvement in Ely A, Evans J, Sundstrom JM, Malysz J, Specht CS, Wilkinson M. Orbital involvement in extranodal natural killer T cell lymphoma: an atypical case presentation and review of the extranodal natural killer T cell lymphoma: an atypical case presentation and review of the literature. Orbit. 2012 Aug;31(4):267-9.literature. Orbit. 2012 Aug;31(4):267-9.

2.2.Ferry JA, Fung CY, Zukerberg L, Lucarelli MJ, Hasserjian RP, Preffer FI, Harris NL. Ferry JA, Fung CY, Zukerberg L, Lucarelli MJ, Hasserjian RP, Preffer FI, Harris NL. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb;31(2):170-84.Feb;31(2):170-84.

3.3.Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. The World Health Organization classification of neoplasms of the Bloomfield CD. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. Hematol J. 2000;1(1):53-66Airlie House, Virginia, November, 1997. Hematol J. 2000;1(1):53-66

4.4.Hon et al. Vision-threatening Complications of Nasal T/NK Lymphoma. American Journal of Hon et al. Vision-threatening Complications of Nasal T/NK Lymphoma. American Journal of Ophthalmology 2002; 134 (3): 407-410. Ophthalmology 2002; 134 (3): 407-410.

5.5.Jaffe ES, Chan JK, Su IJ, Frizzera G, Mori S, Feller AC, Ho FC. Report of the Workshop on Jaffe ES, Chan JK, Su IJ, Frizzera G, Mori S, Feller AC, Ho FC. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20(1):103.differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20(1):103.

6.6.Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification. Am J Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification. Am J Ophthalmol. 2008 Jun;145(6):941-50. Ophthalmol. 2008 Jun;145(6):941-50.

7.7.Kanavaros P, Lescs MC, Brière J, Divine M, Galateau F, Joab I, Bosq J, Farcet JP, Reyes F, Kanavaros P, Lescs MC, Brière J, Divine M, Galateau F, Joab I, Bosq J, Farcet JP, Reyes F, Gaulard P. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar Gaulard P. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood. 1993;81(10):2688.phenotype and with Epstein-Barr virus. Blood. 1993;81(10):2688.

8.8.Woog JJ, Kim YD, Yeatts RP, Kim S, Esmaeli B, Kikkawa D, Lee HB, Korn BS, Punja K, Woog JJ, Kim YD, Yeatts RP, Kim S, Esmaeli B, Kikkawa D, Lee HB, Korn BS, Punja K, Habermann TM, Colgan JP, Salomao D, Cameron JD. Natural killer/T-cell lymphoma with Habermann TM, Colgan JP, Salomao D, Cameron JD. Natural killer/T-cell lymphoma with ocular and adnexal involvement. Ophthalmology. 2006 Jan;113(1):140-7ocular and adnexal involvement. Ophthalmology. 2006 Jan;113(1):140-7