medical grandrounds

MEDICAL MEDICAL GRANDROUNDSGRANDROUNDS

Marion Priscilla B. Aurellado, Marion Priscilla B. Aurellado, M.D.M.D.

May 22, 2008May 22, 2008

ObjectivesObjectives

To present a case of cerebral To present a case of cerebral toxoplasmosistoxoplasmosis

To discuss an approach to right upper To discuss an approach to right upper extremity weakness in a young, extremity weakness in a young, previously healthy patient with mass previously healthy patient with mass lesions in the brain on imaginglesions in the brain on imaging

To present some epidemiologic data To present some epidemiologic data on the burden of HIV/AIDS in the on the burden of HIV/AIDS in the PhilippinesPhilippines

Identifying DataIdentifying Data

J.E.J.E. 27 year old male27 year old male SingleSingle Filipino Filipino Roman CatholicRoman Catholic From PangasinanFrom Pangasinan

Chief ComplaintChief Complaint

Near syncopal attackNear syncopal attack

History of Present IllnessHistory of Present Illness 3 months3 months Intermittent dizzinessIntermittent dizziness

Light headednessLight headedness No meds/consultNo meds/consult

History of Present IllnessHistory of Present Illness 2 weeks 2 weeks RUE weaknessRUE weakness

Weak hand gripWeak hand grip Orthopedic consult Orthopedic consult

donedone Unrecalled meds givenUnrecalled meds given Advised observationAdvised observation Progression of right Progression of right

weaknessweakness Follow-up consult doneFollow-up consult done EMG-NCV advised, but EMG-NCV advised, but

not donenot done

History of Present IllnessHistory of Present Illness

2 days2 days

AdmissionAdmission

generalized body generalized body weaknessweakness

Near syncopal Near syncopal attackattack

Clinic consult doneClinic consult done Hypotensive at Hypotensive at

80/6080/60 Advised admissionAdvised admission

Review of SystemsReview of Systems (+) weight loss ~ 30 (+) weight loss ~ 30

lbs in 4 monthslbs in 4 months (+) undocumented (+) undocumented

intermittent fever & intermittent fever & chills since 4 chills since 4 monthsmonths

(+) anorexia(+) anorexia (+) hair loss(+) hair loss (-) headache(-) headache (-) loss of (-) loss of

consciousnessconsciousness (-) cough or colds(-) cough or colds

(-) chest pain(-) chest pain (-) dyspnea(-) dyspnea (-) palpitations(-) palpitations (-) abdominal pain(-) abdominal pain (-) nausea or (-) nausea or

vomitingvomiting (-) LBM/constipation(-) LBM/constipation (-) melena(-) melena (-) hematochezia(-) hematochezia (-) dysuria(-) dysuria (-) hematuria(-) hematuria

Past Medical HistoryPast Medical History

No asthmaNo asthma No DMNo DM No history of hepatitisNo history of hepatitis No previous hospitalizations No previous hospitalizations No history of blood transfusionsNo history of blood transfusions No known food or drug allergiesNo known food or drug allergies

Family HistoryFamily History

(+) DM(+) DM

Social HistorySocial History

Non-smokerNon-smoker Occasional alcoholic beverage Occasional alcoholic beverage

drinkerdrinker No illicit drug useNo illicit drug use

Physical ExaminationPhysical Examination General Survey: General Survey:

Conscious, coherent, not in respiratory Conscious, coherent, not in respiratory distressdistress

Vital Signs:Vital Signs:BP lying: 100/60 BP sitting: 100/60 BP lying: 100/60 BP sitting: 100/60 BP standing: 80/50BP standing: 80/50 CR 88 RR 18 CR 88 RR 18 afebrileafebrile

HEENT:HEENT:Pink palpebral conjunctivae, anicteric Pink palpebral conjunctivae, anicteric sclerae, (-) tonsillopharyngeal congestion, sclerae, (-) tonsillopharyngeal congestion, (-) cervical lymphadenopathies(-) cervical lymphadenopathies

Physical ExaminationPhysical Examination Chest & Lungs:Chest & Lungs:

Symmetric chest expansion, clear Symmetric chest expansion, clear breath soundsbreath sounds

CVS:CVS:Adynamic precordium, normal rate, Adynamic precordium, normal rate, regular rhythm, no murmursregular rhythm, no murmurs

Abdomen:Abdomen:Flat abdomen, normoactive bowel Flat abdomen, normoactive bowel sounds, no tenderness, no sounds, no tenderness, no organomegalyorganomegaly

Physical ExaminationPhysical Examination

Extremities:Extremities:

Full and equal pulses, no edema, Full and equal pulses, no edema, (+) (+) purplish skin rash all over, (+) purplish skin rash all over, (+) atrophy of dorsal interossei muscles atrophy of dorsal interossei muscles of right hand (claw hand of right hand (claw hand appearance), (+) subcutaneous appearance), (+) subcutaneous nodules in all extremitiesnodules in all extremities

Neurologic ExaminationNeurologic Examination Mental Status ExamMental Status Exam::

awake, oriented to 3 spheresawake, oriented to 3 spheresno memory lapses, good attentionno memory lapses, good attentionintact repetition, recall 3/3intact repetition, recall 3/3no aphasia, no R-L disorientationno aphasia, no R-L disorientation

Neurologic ExaminationNeurologic Examination Cranial NervesCranial Nerves::

CN I - intactCN I - intactCN II – pupils 3-4 mm EBRTL, visual CN II – pupils 3-4 mm EBRTL, visual

fields intactfields intactCN III, IV, VI – primary gaze midline, CN III, IV, VI – primary gaze midline,

full EOMsfull EOMsCN V – intact V1-V3CN V – intact V1-V3CN VII – no facial asymmetryCN VII – no facial asymmetryCN VIII - intactCN VIII - intactCN IX, X – intact gagCN IX, X – intact gagCN XI – good SCM toneCN XI – good SCM toneCN XII – tongue midlineCN XII – tongue midline

Neurologic ExaminationNeurologic Examination

SensorySensory: Intact to all modalities: Intact to all modalities Motor:Motor: 5/5 on both lower extremities 5/5 on both lower extremities

and LUEand LUE

RUE: RUE: 5-/5 shoulder abduction5-/5 shoulder abduction4/5 shoulder adduction4/5 shoulder adduction4/5 Shoulder extension4/5 Shoulder extension5-/5 shoulder flexion5-/5 shoulder flexion5-/5 elbow flexion5-/5 elbow flexion4/5 elbow extension4/5 elbow extension

Neurologic ExaminationNeurologic Examination

CerebellumCerebellum: No dysdiadochoinesia, : No dysdiadochoinesia, no dysmetria, able to walk in no dysmetria, able to walk in tandem, walk on heels and toestandem, walk on heels and toes

Deep Tendon ReflexesDeep Tendon Reflexes: +2 left; : +2 left; +3 +3 right upper extremityright upper extremity, +2 right , +2 right lower extremitylower extremity

Pathologic ReflexesPathologic Reflexes: no Babinski: no Babinski MeningesMeninges: no nuchal rigidity: no nuchal rigidity

Salient FeaturesSalient Features 27 year old male27 year old male Previously healthyPreviously healthy Right upper extremity weakness, Right upper extremity weakness,

dizzinessdizziness Significant weight loss & anorexiaSignificant weight loss & anorexia Intermittent feverIntermittent fever Generalized skin rashGeneralized skin rash Atrophy of dorsal interossei muscles of Atrophy of dorsal interossei muscles of

right hand (claw hand appearance)right hand (claw hand appearance) Subcutaneous nodules in all extremitiesSubcutaneous nodules in all extremities

Where is the Lesion?Where is the Lesion?

Focal peripheral nerve involvementFocal peripheral nerve involvement

What is the Nature of the What is the Nature of the Lesion?Lesion?

MetabolicMetabolic InflammatoryInflammatory TraumaTrauma

Thomas PK, Ochoa J. Symptomatology and differential Thomas PK, Ochoa J. Symptomatology and differential diagnosis of peripheral neuropathy. In: Dyck PJ, Thomas diagnosis of peripheral neuropathy. In: Dyck PJ, Thomas PK, eds. Peripheral neuropathy. Philadelphia: Saunders, PK, eds. Peripheral neuropathy. Philadelphia: Saunders,

1993:749-74. 1993:749-74.

Admitting ImpressionAdmitting Impression

Connective Tissue DiseaseConnective Tissue Disease

Course in the WardsCourse in the Wards

12 L ECG 12 L ECG Stat 5Stat 5 IV Fluids startedIV Fluids started ESR and ANAESR and ANA EMG-NCVEMG-NCV

11stst Hospital Day Hospital Day

BP stable 100-110/60-70BP stable 100-110/60-70 No dizzinessNo dizziness (+) R arm weakness(+) R arm weakness ESR 120ESR 120 ImpressionImpression: Connective tissue : Connective tissue

disease disease

22ndnd Hospital Day Hospital Day

Prednisone startedPrednisone started EMG NCV R arm - NORMALEMG NCV R arm - NORMAL ANA negativeANA negative

ImpressionImpression: Connective tissue : Connective tissue disease ruled outdisease ruled out

22ndnd Hospital Day Hospital Day

Repeat CBCRepeat CBC Anemia & eosinophiliaAnemia & eosinophilia

Fecalysis Fecalysis Dermatology referral: Skin biopsyDermatology referral: Skin biopsy ImpressionImpression: Parasitic infection: Parasitic infection MRI & MRA with GadoliniumMRI & MRA with Gadolinium

Salient FeaturesSalient Features

Subcutaneous nodules in all Subcutaneous nodules in all extremitiesextremities

Anemia, eosinophiliaAnemia, eosinophilia Multiple ring enhancing lesions on Multiple ring enhancing lesions on

cranial MRIcranial MRI

ImpressionImpression: : T/C NeurocysticercosisT/C Neurocysticercosis

R/O CNS MalignancyR/O CNS Malignancy

Multiple Ring Enhancing Lesions on MRI

InfectiousNeoplastic

Primary Metastatic



Bacterial Abscess

Tuberculoma

Neurocysticercosis

ToxoplasmosisCryptococcus

Primary CNS LymphomaPrimary CNS Lymphoma Present with one of 3 syndromesPresent with one of 3 syndromes

Subacute progression of focal neurologic Subacute progression of focal neurologic deficitdeficit

SeizureSeizure Nonfocal neurologic deficit: HeadacheNonfocal neurologic deficit: Headache

Fever, malaise, weight loss, anorexia Fever, malaise, weight loss, anorexia suggest metastatic more than primarysuggest metastatic more than primary

Uniformly enhancing mass lesion in Uniformly enhancing mass lesion in immunocompetentimmunocompetent

Ring enhancing in the Ring enhancing in the immunocompromisedimmunocompromised

Metastatic Brain TumorsMetastatic Brain Tumors

Most commonly originates from:Most commonly originates from: Lung CALung CA Breast CABreast CA GI malignancyGI malignancy Melanoma Melanoma

Bacterial Brain Abscess

Cause: Cause: StreptococcusStreptococcus (40%) (40%), , Anaerobes, Anaerobes, Staphylococcus Staphylococcus (10%)(10%)

Associated with otitis, mastoiditis, dental Associated with otitis, mastoiditis, dental infections or head traumainfections or head trauma

Headache is the most common symptom Headache is the most common symptom in >75% of casesin >75% of cases

Classic triad of headache, fever, and focal Classic triad of headache, fever, and focal neurologic deficitneurologic deficit

Multiple Multiple hematogenous hematogenous poorly poorly encapsulatedencapsulated

TuberculomaTuberculoma

Uncommon manifestation of CNS Uncommon manifestation of CNS tuberculosistuberculosis

Cause: Cause: Mycobacterium tuberculosisMycobacterium tuberculosis Transmission: Hematogenous spread Transmission: Hematogenous spread

from a primary pulmonary or from a primary pulmonary or postprimary pulmonary diseasepostprimary pulmonary disease

Seizures or focal neurologic deficitsSeizures or focal neurologic deficits Diagnosis: AFB on CSFDiagnosis: AFB on CSF

NeurocysticercosisNeurocysticercosis

Cause: Cause: Taenia soliumTaenia solium Transmission: Ingestion of Transmission: Ingestion of

undercooked porkundercooked pork Cysticerci found anywhere in the body Cysticerci found anywhere in the body

but are commonly in:but are commonly in: BrainBrain CSFCSF Skeletal muscleSkeletal muscle Subcutaneous tissueSubcutaneous tissue EyeEye

NeurocysticercosisNeurocysticercosis

Often presents with seizures and Often presents with seizures and signs of increased intracranial signs of increased intracranial pressurepressure

Diagnosis:Diagnosis:FecalysisFecalysisNeuroimaging Neuroimaging Evidence of cysticercosis outside Evidence of cysticercosis outside

the CNSthe CNS

CryptococcosisCryptococcosis

Cause: Cause: Cryptococcus neoformansCryptococcus neoformans Transmission: Transmission: inhalation of yeast from

the environment (bird droppings) Risk factor: CD4 < 100 Presents with headache, fever, cranial

nerve paresis, and meningeal irritation

Diagnosis: India ink stain, CALAS

ToxoplasmosisToxoplasmosis

Cause: Cause: Toxoplasma gondiiToxoplasma gondii Transmission: Transmission: Ingestion of faecally c Ingestion of faecally c

ontaminated material ontaminated material, , Ingestion of u Ingestion of u ndercooked meat ndercooked meat

Risk factor: CD4 < 100Risk factor: CD4 < 100 Asymptomatic in immunocAsymptomatic in immunocompetent ompetent

peoplepeople

ToxoplasmosisToxoplasmosis

In immunocompromised, mainly In immunocompromised, mainly involve the CNSinvolve the CNS Altered mental status (75%)Altered mental status (75%) Focal neurologic deficits (60%)Focal neurologic deficits (60%) Headaches (56%)Headaches (56%) Seizures (33%)Seizures (33%)

Diagnosis:Diagnosis: Serology: IgG and IgMSerology: IgG and IgM

33rdrd Hospital Day Hospital Day

Mannitol startedMannitol started Lumbar puncture doneLumbar puncture done

Opening pressure 120 cmH2OOpening pressure 120 cmH2O ClearClear WBC 2 Lymphocytes 2 RBC 0WBC 2 Lymphocytes 2 RBC 0 Sugar 64 (nv 40-75); Protein 47.4 (15-45)Sugar 64 (nv 40-75); Protein 47.4 (15-45) No organisms or pus cellsNo organisms or pus cells Negative for AFB, India Ink, KOH, Negative for AFB, India Ink, KOH,

CALASCALAS Dexamethasone startedDexamethasone started

44thth Hospital Day Hospital Day

X-ray of the left femur – NORMALX-ray of the left femur – NORMAL Infectious Diseases referralInfectious Diseases referral History of unprotected sex with History of unprotected sex with

multiple sexual partners and multiple sexual partners and bisexual contactsbisexual contacts

HIV screeningHIV screening Whole abdomen UTZ – NORMALWhole abdomen UTZ – NORMAL



Primary Metastatic



Bacterial Abscess

Tuberculoma

Neurocysticercosis

ToxoplasmosisCryptococcus


CD4 countCD4 count Serum CALAS Serum CALAS Toxoplasma IgG Toxoplasma IgG Toxoplasma IgMToxoplasma IgM


Discharged, awaiting final report:Discharged, awaiting final report: Serum CALAS Serum CALAS Toxoplasma IgG Toxoplasma IgG Toxoplasma IgMToxoplasma IgM CD4 titers and HIV testCD4 titers and HIV test

Patient OutcomePatient Outcome

HIV (+); CD4 = 53HIV (+); CD4 = 53 Toxoplasma IgG 3.8 (nv <2)Toxoplasma IgG 3.8 (nv <2) Toxoplasma IgM 0.34 (nv <0.5)Toxoplasma IgM 0.34 (nv <0.5) Serum CALAS NEGATIVESerum CALAS NEGATIVE

Clinical CorrelationClinical CorrelationToxoplasmosisToxoplasmosis Patient JEPatient JE

Nonfocal to focal Nonfocal to focal neurologic deficitsneurologic deficits

Motor deficit (RUE)Motor deficit (RUE)

Meningeal Meningeal involvement involvement uncommonuncommon

Absence of Absence of meningismusmeningismus

CSF often CSF often unremarkable, may unremarkable, may have modest increase have modest increase in cell count & in cell count & protein but normal protein but normal glucoseglucose

Sugar 64 (nv 40-75); Sugar 64 (nv 40-75); Protein 47.4 (15-45)Protein 47.4 (15-45)

CD4 < 100CD4 < 100 CD4: 53CD4: 53

Clinical CorrelationClinical Correlation

ToxoplasmosisToxoplasmosis Patient JEPatient JE

(+) IgG titers (+) IgG titers detected as early as detected as early as 2-3 weeks after 2-3 weeks after infectioninfection

Toxoplasma IgG 3.8 Toxoplasma IgG 3.8 (<2)(<2)

Toxoplasma IgM Toxoplasma IgM normalnormal

Multiple discrete Multiple discrete high signal foci, high signal foci, heterogenous w/ heterogenous w/ well-circumscribed well-circumscribed margins, and margins, and hyperintense on post hyperintense on post contrast MRIcontrast MRI

Multiple ring Multiple ring enhancing lesions enhancing lesions with vasogenic with vasogenic edema in both edema in both cerebral hemispheres cerebral hemispheres at the at the corticomedullary corticomedullary marginmargin

Final DiagnosisFinal Diagnosis

Cerebral ToxoplasmosisCerebral Toxoplasmosis HIV infectionHIV infection Atopic DermatitisAtopic Dermatitis

ManagementManagement Toxoplasmosis is rapidly fatal if untreatedToxoplasmosis is rapidly fatal if untreated Treatment of choice:Treatment of choice:

PyrimethaminePyrimethamine plus plus folinic acid folinic acid plus plus sulfadiazisulfadiazinene

PyrimethaminePyrimethamine plus plus folinic acid folinic acid plus plus clindamycclindamycinin

1992Danneman et al. Ann Intern Med ; 1992Danneman et al. Ann Intern Med ;1116316333-43.-43. 6 weeks therapy at least, or until 3 weeks after 6 weeks therapy at least, or until 3 weeks after

complete scan resolution complete scan resolution Corticosteroids for raised intracranial pressure Corticosteroids for raised intracranial pressure

-1989 86 5217Cohn et al. Am J Med ; : -1989 86 5217Cohn et al. Am J Med ; :

ManagementManagement

Oral co-trimoxazole is effective in doses of 2 tablets 4 times daily for 1 month followed by 2 tablets twice daily as secondary prophylaxis for life

Lifetime prophylactic therapy for toxoplasmosis would only apply if patients are not receiving antiretroviral therapy with the CD4 count being under 200 cells/μl

P Francis, January 2004, Vol. 94, No. 1 S Afr Med J

HIV Ab Seropositives by YearHIV Ab Seropositives by YearHIV/AIDS Registry, January 1984-July HIV/AIDS Registry, January 1984-July

2007 (N=2,9162007 (N=2,916

HIV Ab Seropositives by Gender and HIV Ab Seropositives by Gender and Age GroupAge Group

HIV/AIDS Registry, January 1984-July HIV/AIDS Registry, January 1984-July

2007 (N=2,916)2007 (N=2,916)

Reported Modes of TransmissionReported Modes of TransmissionHIV/AIDS Registry, January 1984-July HIV/AIDS Registry, January 1984-July

2007 (N=2,916)2007 (N=2,916)

ModeMode Jan 84 -July 07Jan 84 -July 07 July 07July 07

Heterosexual Heterosexual ContactContact

17811781 1010

Homosexual Homosexual ContactContact

567567 99

Bisexual Bisexual ContactContact

200200 99

Blood/Blood Blood/Blood productproduct

1919 00

IV drug useIV drug use 77 00

Reported Modes of TransmissionReported Modes of TransmissionHIV/AIDS Registry, January 1984-July HIV/AIDS Registry, January 1984-July

2007 (N=2,916)2007 (N=2,916)

Needle prick Needle prick injuriesinjuries

33 00

PerinatalPerinatal 4444 00

No exposure No exposure reportedreported

295295 33

TOTALTOTAL 29162916 3131

Patient OutcomePatient Outcome

Readmitted after 2 weeks for seizureReadmitted after 2 weeks for seizure Started on Co-trimoxazole and ARTsStarted on Co-trimoxazole and ARTs Discharged against medical adviceDischarged against medical advice Went back to PangasinanWent back to Pangasinan Lost to follow-upLost to follow-up AMD notified by company physician AMD notified by company physician

that the patient expiredthat the patient expired

Thank you!!!Thank you!!!

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