imaging in neurocysticercosis sarun sarun charumilind...

Imaging in Imaging in NeurocysticercosisNeurocysticercosis

SarunSarun CharumilindCharumilind, , Harvard Medical School, Year IIIHarvard Medical School, Year III

Gillian Lieberman, MDGillian Lieberman, MD

September September 20042004

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Index PatientIndex Patient

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Index Patient: Mr. CPIndex Patient: Mr. CP

Mr. CP is a previously healthy 25 Mr. CP is a previously healthy 25 y.oy.o. man who . man who immigrated from Cape Verde in 1995 and who immigrated from Cape Verde in 1995 and who presents to an outside hospital with:presents to an outside hospital with:

55--day history of progressively severe headaches and day history of progressively severe headaches and h/oh/ochronic HA x4 yrs, relieved with change in positionchronic HA x4 yrs, relieved with change in position2 days of 2 days of ““forgetfulnessforgetfulness””Appearance of agitation and nervousnessAppearance of agitation and nervousness

No significant PMH, allergies, meds.No significant PMH, allergies, meds.No c/o of N/V, incontinence, visual, speech, No c/o of N/V, incontinence, visual, speech, personality changes. personality changes. Given Demerol and Given Demerol and PhenerganPhenergan..CT and MRI with gadolinium are ordered. CT and MRI with gadolinium are ordered.

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Index Pt.: Imaging at Outside HospitalIndex Pt.: Imaging at Outside HospitalHydrocephalus Hydrocephalus Third ventricular Third ventricular lesion lesion -- ?cyst?cystTransferred to Transferred to BIDMCBIDMCOpening Opening pressure > 30pressure > 30L. frontal L. frontal ventriculostomyventriculostomyand drain and drain placementplacementRepeat CT/MRIRepeat CT/MRI

Hydrocephalus of lateral ventricles

Third ventricular cyst: transverse cut

Third ventricular cyst: coronal cut

Third ventricular cyst: sagittal cut

Images from PACS, BIDMC

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Index Pt: BIDMC Imaging: Index Pt: BIDMC Imaging: CT & MRI w/ GadCT & MRI w/ Gad

Mild, diffusely Mild, diffusely enlarged ventricles enlarged ventricles esp. at third esp. at third ventriculeventriculeand temporal hornsand temporal hornsEffaced Effaced sulcisulciScattered Scattered calcifications along calcifications along sulcisulci ( R ( R ponspons, R post. , R post. frontal lobe)frontal lobe)Third ventricular cyst Third ventricular cyst with enhancementwith enhancement


Hydrocephalus of lateral ventricles (CT) Calcification in right pons (CT)

Calcification in right parietal lobe (CT)3rd ventricular cyst (MR, post-gad)

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Differential DiagnosisDifferential DiagnosisObstructive Obstructive

HydrocephaluHydrocephalu ssTumor: benign Tumor: benign or malignantor malignantCyst (colloid, Cyst (colloid, arachnoidarachnoid, , PARASITIC) PARASITIC) AbscessAbscessCongenitalCongenitalMultiple Multiple sclerosissclerosisTuberous Tuberous sclerosissclerosis

Cyst With Mural Cyst With Mural NoduleNoduleTumor: benign or Tumor: benign or malignant malignant ((gangliogliomaganglioglioma, , GBM, GBM, astrocytomaastrocytoma))MetastasisMetastasisPARASITIC cyst PARASITIC cyst ((cysticercuscysticercus, , paragonimusparagonimus))

Multiple Multiple Intracranial Intracranial CalcificationsCalcificationsAtherosclerosisAtherosclerosisIdiopathicIdiopathicPhysiologic Physiologic ((duradura, choroid , choroid plexiplexi, pineal , pineal gland)gland)PARASITIC PARASITIC ((cysticercosiscysticercosis, , paragonimusparagonimus))

Reeder MM and B Felson, Gamuts in Radiology, 2003.

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Hospital Course & FollowHospital Course & Follow--upupSURG: Right SURG: Right transcallosaltranscallosal cyst cyst resection resection –– brown, tan colored cyst brown, tan colored cyst removedremovedIMAGING: resolved hydrocephalusIMAGING: resolved hydrocephalusW/U: W/U:

ID consult: PPD neg., no growth ID consult: PPD neg., no growth in serum or CSF, no AFB, in serum or CSF, no AFB, positive positive for CC Absfor CC AbsOpthoOptho consult: no intraocular consult: no intraocular SxSxPathology: confirmed NCCPathology: confirmed NCC

TX: Treated with TX: Treated with albendazolealbendazole x 7d + x 7d + decadrondecadronDISCHARGE DX: DISCHARGE DX: NeurocysticercosisNeurocysticercosisF/U: headaches resolved, discuss PPX F/U: headaches resolved, discuss PPX if return to Cape Verdeif return to Cape Verde


Index Pt: Resolution of hydrocephalus (CT)

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TaeniaTaenia SoliumSolium: Parasite of the Poor: Parasite of the PoorMost common Most common helminthichelminthicinfection of CNSinfection of CNSBased on lifecycle, is facilitated Based on lifecycle, is facilitated only in poor living conditionsonly in poor living conditionsEndemic to many regions: Endemic to many regions: Mexico, Central and South Mexico, Central and South America, subAmerica, sub--Saharan Africa, Saharan Africa, AsiaAsiaHigher prevalence in rural Higher prevalence in rural areas (10areas (10--25%)25%)High prevalence in highHigh prevalence in high--porkpork--consuming/consuming/--raising countriesraising countries50,000 deaths/yr, 20 million 50,000 deaths/yr, 20 million infectedinfectedMost common cause of Most common cause of acquired epilepsy acquired epilepsy worldwideworldwideUnited States: ~1000 cases United States: ~1000 cases per yearper year

Global prevalence of Taenia solium

ftp://ftp.cdc.gov/pub/infectious_diseases/iceid/2002/pdf/schantz.pdf

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TaeniaTaenia SoliumSolium: Lifecycle: Lifecycle

http://www.ucm.es/inf o/parasito/Taenia%20

escolex.jpg

http://www.dpd.cdc.gov/dpdx/HTML/Cysticercosis.htm

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CysticercosisCysticercosis: Clinical Manifestations: Clinical ManifestationsSymptomatic Cysticercosis

Neurocysticercosis Extraneural Cysticercosis•Eye•Muscle

Extraparenchymal•Intraventricular•Subarachnoid•Spinal

Parenchymal

Pt. #5: Intraocular*

Pt. #2: Muscular (tongue)*

Pt. #4: Subcutaneous**Pt. #3: Parenchymal**

Images from *http://www.facmed.unam.mx/grid/photos.htm and **http://faculty.uaeu.ac.ae/~youssefa/homepage/taenia.htm

•Subcutaneous

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NCC: NCC: PathophysiologyPathophysiologyNeurocysticercosis

20% Symptomatic•Mass effects•Inflammatory response•Foraminal obstruction•Ventricular obstruction

80% Asymptomatic

Degree of Sx depends on:•Lifecycle stage•Site•Number of cysts

Life Stages of T. Solium

Cysticerci•Asymptomatic•Host immune tolerance•Duration: 3-5 yrs

Degenerating•Inflammatory response•Cyst loses ability to moderate immune response•Active NCC

Inactive•Calcified•Asymptomatic•Potential epileptic/obstructive focus

Tx depends on Sx1. Meds: antiparasitic, antiinflammatory,

anticonvulsant2. Surgery3. Nothing!

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Stage 1: Vesicular CystsStage 1: Vesicular CystsCTCT: Small, rounded, : Small, rounded,

wellwell--demarcated, demarcated, lowlow--density w/o density w/o edema.edema.

MRIMRI: signal similar to CSF : signal similar to CSF in T1 and T2; in T1 and T2; scolexscolex seen seen in cyst: “holein cyst: “hole--withwith--dot” or dot” or ““swissswiss cheese” if severe.cheese” if severe.

Pt. #6: Head CT w/ contrast Pt. #7: MRI w/o contrast

Images from Garica HH and Del OH Bruto, 2003.

Pt. #8: MRI w/o contrast

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Stage 2: Colloidal CystsStage 2: Colloidal Cysts

CTCT: : illill--defined with edema, defined with edema, ring pattern with contrast = ring pattern with contrast = acute encephalitic phaseacute encephalitic phase

MRIMRI: thick : thick hypointensehypointensewall + wall + perilesionalperilesionalhyperintensehyperintense edemaedema

CysticercoticCysticercotic EncephalitisEncephalitis: : diffuse edema + collapsed diffuse edema + collapsed ventricles + multiple lesions = ventricles + multiple lesions = young cysts attacked by hostyoung cysts attacked by host

Pt. #10: Cysticercotic Encephalitis

Pt. #9: Colloidal cyst on MRI


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Stage 3: Granular Cysts & Stage 4: Stage 3: Granular Cysts & Stage 4: Calcified CystsCalcified Cysts

CTCT: : granulomatousgranulomatous

MRIMRI: : signal void + signal void + hyperhyper-- intense edematous intense edematous rimrim

CTCT: : small, small, hyperdensehyperdensenodules w/o edema unless nodules w/o edema unless relapserelapse

MRIMRI: : edema with high edema with high signal surrounding low signal surrounding low signal cystsignal cyst

Granular Calcified


Pt. #11: “Single enhancing lesion” on CTPt. #12: MRI: Signal void w/ surrounding edema

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Other Cyst LocationsOther Cyst LocationsSubarachnoidSubarachnoid: large, : large, multimulti--lobulatedlobulated

VentricularVentricular: best on : best on MRI, MRI, isodenseisodense on CTon CT

SpinalSpinal: nonspecific : nonspecific enlargement, filling enlargement, filling defects on defects on myelogrammyelogram


Pt. #13: Giant cyst in

Sylvian fissure

Pt. #14: Ventricular cysts

on MRI FLAIR

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Comparing ModalitiesComparing Modalities

Index Pt: Close-up views of mural nodule cyst: cysticercus with scolex inside (MRI)


•Plain film: Rarely used (incidental subQ and muscle Ca++)•CT v. MRI: Depends on stage•CT: Cheaper, better at Ca++•MRI:

•Better sensitivity (esp. active cysts, cysts in post. fossa)•Better scolex visualization•Not widely available globally

•Approach: CT first, then MRI if inconclusive, strong suspicion, or follow-up.

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Other Diagnostic WorkupOther Diagnostic Workup

SerologySerologyTargetsTargets: : AntiCCAntiCC antibodies or antibodies or cysticercalcysticercal antigensantigensSubstratesSubstrates: CSF, saliva, or blood: CSF, saliva, or bloodMethodsMethods: ELISA, complement : ELISA, complement fixation, fixation, immunoblotimmunoblot, etc., etc.StandardStandard: Enzyme: Enzyme--linked linked immunoblotimmunoblot, detect , detect antiCCantiCC AbsAbs

PathologyPathologyWhite fluidWhite fluid--filled bladder 5filled bladder 5--10 mm 10 mm diamterdiamter w/ solid 2 mm larval w/ solid 2 mm larval tapewormtapeworm

Pt: #15: Taenia solium egg

Pt. #16: Electron microscopy of an egghttp://www.biosci.ohio-state.edu/~parasite/taenia.html

http://www.facmed.unam.mx/grid/photos.htm

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Diagnostic CriteriaDiagnostic Criteria1.1. AbsoluteAbsolute: :

HistologicHistologicScolexScolex on imagingon imagingOcular signsOcular signs

2.2. MajorMajor: : Lesions “suggestive” on Lesions “suggestive” on imagingimagingPositive serology for AbsPositive serology for AbsImprovement after Improvement after treatmenttreatmentSpontaneous resolution of Spontaneous resolution of single lesionsingle lesion

3.3. MinorMinor: : Lesions “compatible” on Lesions “compatible” on imagingimagingClinical signs “suggestive”Clinical signs “suggestive”Positive serology for Abs or Positive serology for Abs or AgsAgsCC outside CNSCC outside CNS

4. 4. EpidemiologicEpidemiologic: : Household contactHousehold contactGeographic correlationGeographic correlationTravel correlationTravel correlation

DiagnosisDiagnosis::Definitive: Definitive:

1 absolute + 1 1 absolute + 1 epiepi2 major + 1 minor + 2 major + 1 minor + 1 1 epiepi

Probably: Probably: 1 major + 2 minor1 major + 2 minor1 major + 1 minor + 1 major + 1 minor + 1 epidemiologic1 epidemiologic3 minor + 1 3 minor + 1 epidemiologicepidemiologic

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The International Debate over CriteriaThe International Debate over CriteriaIn the setting of many countries with endemic NCC…

• Biopsy: not possible to perform in all suspected pts.• Ocular: direct visualization rare, hardly reported• Scolex: uncommon on CT/MRI• Epi: majority of Indians have single enhancing, yet this is only a “major” criteria• Different DDX: CNS tuberculosis, with also single/multiple tuberculoma that

show as multiple enhancing CT/MRI lesions, similar to NCC; also multiple tuberculoma, fungal granuloma, primary or secondary malignancies, and multiple pyogenic abscesses

• Serology: EITB (Ab immunoblot) not available, not sensitive• Tx: albendazole/praziquantel may not be effective, and tx role is unclear• “Minor” and “Epi” Criteria: not specific enough?

Current criteria more suitable for the patients in regions whereboth NCC and other CNS infections are uncommon, as opposedto India or other developing countries, which have highprevalence of these.

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A Patient with MVA 2° to SeizureA Patient with MVA 2° to Seizure

Mr. EMMr. EM: previously : previously healthy 33 healthy 33 yoyo man from man from Cape Verde, struck Cape Verde, struck another vehicle at 80 another vehicle at 80 mph.mph.Seized at scene of MVA Seized at scene of MVA and outside the ER.and outside the ER.ImagingImaging: Trauma, : Trauma, Spine, Head series: No Spine, Head series: No fracturesfracturesNCHCTNCHCT: 8 small : 8 small calcifications without calcifications without edemaedemaTXTX: Seizure control. No : Seizure control. No surgery.surgery.


Pt.#17: Cacification in posterior fossa (CT)Pt.#17: MR, susceptibility, of same lesion

Pt.#17: T2 MR of same lesionPt.#17: Calcification near cranial vertex (CT)

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A Patient with MVA 2° to A Patient with MVA 2° to Seizure (cont.)Seizure (cont.)

Remember!In developing regions of the world, seizure is a common first presentation of NCC. NCC is the most common cause of adult-onset acquired epilepsy worldwide.

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A Patient with Incidental NCC?A Patient with Incidental NCC?Mr. RBMr. RB: 38 : 38 yoyo Nepali man with seizure and head traumaNepali man with seizure and head traumaNCHCTNCHCT: Ventricular and : Ventricular and parenchymalparenchymal calcifications calcifications DDXDDX: : EtOHEtOH withdrawal v. NCCwithdrawal v. NCC


Pt.#18: Multiple parenchymal and ventricular calcifications (noncontrast CT)

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A Patient with Incidental NCC? A Patient with Incidental NCC? (cont.)(cont.)

Remember!Though calcifications may cause obstruction or serve as seizure foci, more often than not, they cause no pathology. 80% of persons with NCC are asymptomatic.

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A Patient with A Patient with ArachnoiditisArachnoiditis 2° 2° to NCCto NCC

Mr. MBMr. MB: 52 : 52 yoyo Cape Cape Verdean man with Verdean man with previous previous DxDx of NCC of NCC with 4with 4thth ventricular ventricular cyst removalcyst removalPresentsPresents: severe HA, : severe HA, fever, and LLE fever, and LLE radicularradicular pain, neck pain, neck stiffness, blurry visionstiffness, blurry visionImagingImaging: Obstructive : Obstructive hydrocephalus + hydrocephalus + spinal cord spinal cord inflammationinflammationTXTX: Anti: Anti--TB for TB for meningitis without meningitis without success (misdiagnosis success (misdiagnosis of TB)of TB)


Pt.#19: T1-T2 enhancement (T1 MR)Pt.#19: Cervicomedullary enhancement (T1 MR)

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ArachnoiditisArachnoiditis 2° to NCC (cont.)2° to NCC (cont.)ArachnoiditisArachnoiditis: spinal cord inflammation evidenced by : spinal cord inflammation evidenced by nerve root clumping and adhesions to nerve root clumping and adhesions to thecalthecal sacsacDXDX: Hydrocephalus 2° to impaired CSF absorption from : Hydrocephalus 2° to impaired CSF absorption from CSF inflammatory process CSF inflammatory process NeurocysticercosisNeurocysticercosis


Pt.#19: Lumbosacral involvement: clumping and adhesions (T1 MR, post gad)

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ArachnoiditisArachnoiditis 2° to NCC (cont.)2° to NCC (cont.)

Remember!NCC may have spinal manifestations. Despite this patient’s h/o cyst removal, other cysts may have been present in various life stages. Albendazole is only 75-90% effective.* Up to 41% of patients post- treatment may exhibit noninflamed but viable cysts.**

*Takayanagui 1992, *Sotelo 1998, **Garcia 2004

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A Patient with Toxoplasmosis A Patient with Toxoplasmosis v. NCCv. NCC

Mr. HDMr. HD: 33 : 33 yoyo Haitian Haitian man who on his 1man who on his 1--year year anniversary of being anniversary of being diagnosed with diagnosed with HIV/AIDS presents with HIV/AIDS presents with severe headaches, severe headaches, photophobia, blurred photophobia, blurred vision, dizziness, NVx1, vision, dizziness, NVx1, neck pain on movement, neck pain on movement, fevers, chills, sweatsfevers, chills, sweatsImagingImaging: Multiple : Multiple enhancing lesions with enhancing lesions with surrounding edemasurrounding edemaDXDX: DISSEMINATED : DISSEMINATED CEREBRAL CEREBRAL TOXOPLASMOSISTOXOPLASMOSIS


Pt.#20: Noncontrast Head CT showing lesions with edema

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A Patient with Toxoplasmosis v. A Patient with Toxoplasmosis v. NCC (cont.)NCC (cont.)

Remember!The differential for multiple intracranial calcifications is wide. In addition, settings where NCC is highly prevalent are also settings for other infectious pathologies of the brain: toxoplasmosis, lymphoma in HIV patients, TB granulomas, etc.

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ConclusionConclusionImaging findings depend on modality, Imaging findings depend on modality, cysticercuscysticercus stage, and location.stage, and location.Both CT and MRI have a role, but CT is Both CT and MRI have a role, but CT is the best screening tool.the best screening tool.Debatable whether diagnostic criteria work Debatable whether diagnostic criteria work for all global settings (differences in for all global settings (differences in prevalence and technology).prevalence and technology).Diagnosis often requires serologic, clinical, Diagnosis often requires serologic, clinical, pathologic, and epidemiologic correlation.pathologic, and epidemiologic correlation.

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ReferencesReferences

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cysticercosiscysticercosis. N . N EnglEngl J Med 2004 Jan 15;350(3):249J Med 2004 Jan 15;350(3):249--58.58.6.6. Jain V, et al. “Disseminated Jain V, et al. “Disseminated CysticercosisCysticercosis.” .” The Journal of the Association of Physicians of IndiaThe Journal of the Association of Physicians of India. 2000; . 2000;

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praziquantelpraziquantel. Arch . Arch NeurolNeurol 1992 Mar;49(3):2901992 Mar;49(3):290--4. 4. 14.14. Zimmermann AT and WS Jeffries. “Zimmermann AT and WS Jeffries. “TaeniaTaenia SoliumSolium and and NeurocysticercosisNeurocysticercosis.” .” Medical Journal of AustraliaMedical Journal of Australia. .

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AcknowledgementsAcknowledgements

Joe Barry, MDJoe Barry, MDSteve Reddy, MDSteve Reddy, MDBarbara Barbara AppignaniAppignani, MD, MDAndrew Andrew TarulliTarulli, MD, MDDavid Hackney, MDDavid Hackney, MDGillian Lieberman, MDGillian Lieberman, MDPamela Pamela LepkowskiLepkowskiLarry Barbaras, WebmasterLarry Barbaras, Webmaster

imaging in neurocysticercosis sarun sarun charumilind...

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