HEADACHEHEADACHE

Dr. A SundasDr. A Sundas

33 year, African, female33 year, African, femaleRVD, CD4 47, VL97000RVD, CD4 47, VL97000On On RegReg 1b for 3/12 no other past history1b for 3/12 no other past historyProblem; 2/12 H/O Headache, occasional Problem; 2/12 H/O Headache, occasional night sweats & photophobianight sweats & photophobiaTreated at baseline hospital with Treated at baseline hospital with RocephinRocephin10/7, with no improvement in headache.10/7, with no improvement in headache.

►► Clinically;Clinically;►► Pallor, no LAD, jaundice, oral candidiasisPallor, no LAD, jaundice, oral candidiasis►► ApyrexialApyrexial►► GCS 15/15GCS 15/15►► Neck stiffness & photophobia,Neck stiffness & photophobia,►► ? Fundi? Fundi►► No focal neurological signsNo focal neurological signs►► CVS, respiratory & abdominal examination; NADCVS, respiratory & abdominal examination; NAD

►► In essence In essence ►► 33years old african RVD positive female 33years old african RVD positive female

with low CD4 count ,started on with low CD4 count ,started on RegReg 1b 3/12, 1b 3/12, with history of headache & photophobia for with history of headache & photophobia for 2/12 with occasional night sweats was 2/12 with occasional night sweats was treated as bacterial meningitis, with no treated as bacterial meningitis, with no resolution of headache.resolution of headache.

? CONSIDERATIONS? CONSIDERATIONS

►►TBMTBM►►CCMCCM►►Mass lesionMass lesion►►IRISIRIS

INVESTIGATIONSINVESTIGATIONS

FBC FBC WCC 7.5, HGB 8.7, PLT 433 MCV 105WCC 7.5, HGB 8.7, PLT 433 MCV 105

U&EU&E Na 123, K 4.1, Na 123, K 4.1, ClCl 93, CO2 20.4,Ur 3.4, Cr 7693, CO2 20.4,Ur 3.4, Cr 76

LFTsLFTs T T BilBil 09, ALP 62, GGT 78, ALT 33, ALB 2509, ALP 62, GGT 78, ALT 33, ALB 25

COAGULATION PROFILECOAGULATION PROFILE INR 1.1INR 1.1

LDPLDP 255255

►►LUMBER PUNCTURELUMBER PUNCTUREPOLYS 12POLYS 12Lymph nilLymph nilRed cells 20Red cells 20TP 0.69TP 0.69ClCl 111111Glucose 1.25Glucose 1.25Serum glucose 8.1Serum glucose 8.1India ink India ink negnegCLAT CLAT negneg

Opening pressure not recordedOpening pressure not recorded

LOW CSF GLUCOSELOW CSF GLUCOSE

1 Bacterial Meningitis1 Bacterial Meningitis2 TBM2 TBM3 3 CryptococcalCryptococcal meningitismeningitis4 Brain Abcess4 Brain Abcess5 5 LymphomatousLymphomatous meningitis meningitis 6 6 CarcinomatousCarcinomatous MeningitisMeningitis7 Neurocysticercosis7 Neurocysticercosis

►► TB Treatment & TB Treatment & DecadronDecadron►► US Abdomen; no LAD, no US Abdomen; no LAD, no splenicsplenic or liver abnormalityor liver abnormality►► CXRCXR

Patient symptomaticPatient symptomaticLP not suggestive of clear diagnosisLP not suggestive of clear diagnosisCT scan CT scan

►► TB treatment stopped D6 Steroids tapered off.TB treatment stopped D6 Steroids tapered off.►► Toxoplasma serology & neurocysticercus ELISA was Toxoplasma serology & neurocysticercus ELISA was

done.done.►► Headache continued was getting worse.Headache continued was getting worse.

►► X RAY sinuses 15/05X RAY sinuses 15/05►► Was treated as sinusitis with Augmentin IVIWas treated as sinusitis with Augmentin IVI

►►Worsening symptoms were looked at as Worsening symptoms were looked at as psychogenicpsychogenic

►►Psychological assessment Psychological assessment ►►Revealed no psychological issuesRevealed no psychological issues

FUNDOSCOPYFUNDOSCOPYB/L B/L PapilloedemaPapilloedema

2 mass lesions 2 mass lesions 1 in left occipital lobe and with post contrast 1 in left occipital lobe and with post contrast ring enhancement ring enhancement 1 in cerebellum causing mass effect on 1 in cerebellum causing mass effect on quadrigeminal cisternquadrigeminal cistern

DIFFERENTIALSDIFFERENTIALS

►►Toxoplasma EncephalitisToxoplasma Encephalitis►►TuberculomaTuberculoma►►PCNSLPCNSL►►AbcessAbcess

►►TOXOENCEPHALITIS;TOXOENCEPHALITIS;Reactivation of previous infectionReactivation of previous infectionFever, Headache, Focal neurological signs Fever, Headache, Focal neurological signs Seizures & altered mental state.Seizures & altered mental state.surrounding surrounding oedemaoedema & mass effect , & mass effect , RADIOIMAGINGRADIOIMAGINGMultiple lesions, rarely a solitary lesion.Multiple lesions, rarely a solitary lesion.90% ring enhancing.90% ring enhancing.Uncommonly, diffuse encephalitis.Uncommonly, diffuse encephalitis.Frontal, parietal, thalamic, basal ganglia, Frontal, parietal, thalamic, basal ganglia, cerebellarcerebellar & & corticomedullarycorticomedullary juncionjunciondistribution.distribution.

PCNSLPCNSLHeadache, fever, lethargy, memory Headache, fever, lethargy, memory impairment, focal signs & seizures.impairment, focal signs & seizures.80% B symptoms & CD4 <5080% B symptoms & CD4 <50

IMAGINGIMAGINGEqual frequency of solitary & multiple lesions.Equal frequency of solitary & multiple lesions.some degree of irregular & patchy some degree of irregular & patchy enhancement.enhancement.TE like diffuse ring enhancement possible.TE like diffuse ring enhancement possible.Corpus callosum, periventricular & Corpus callosum, periventricular & periependymalperiependymal involvement.involvement.

< 10% posterior < 10% posterior fossafossa involvement( posterior involvement( posterior fossafossa involvement more in infectious involvement more in infectious etiology).etiology).Lesions >4 cm highly likely to be Lesions >4 cm highly likely to be lymphoma.lymphoma.

TUBERCULOMATUBERCULOMACaseous foci within the brain substance, Caseous foci within the brain substance, developing from deep seated tubercle, developing from deep seated tubercle, during recent or remote hematogenous during recent or remote hematogenous bacillimiabacillimia..Clinically may be silent.Clinically may be silent.Single or multiple, enhancing nodular Single or multiple, enhancing nodular lesions.lesions.Can present as mass lesions without any Can present as mass lesions without any evident systemic illness or meningeal evident systemic illness or meningeal involvement.involvement.

NEUROCYSTICERCOSISNEUROCYSTICERCOSIS( parenchymal cysts) ( parenchymal cysts) Appearance depends on stage of disease & Appearance depends on stage of disease & location of the cyst.location of the cyst.Viable cysts appear non enhancing hypo Viable cysts appear non enhancing hypo dense lesions.dense lesions.Degenerating cysts may enhance with Degenerating cysts may enhance with contrast with variable degree of surrounding contrast with variable degree of surrounding edema.edema.Old cysts appear calcific.Old cysts appear calcific.Lodge in basal ganglia or cerebral cortex.Lodge in basal ganglia or cerebral cortex.Different cysts stages may be present .Different cysts stages may be present .Serology aids to diagnosis.Serology aids to diagnosis.

PATIENTPATIENT’’S SCANS SCAN

►► Multiple ring enhancing lesionsMultiple ring enhancing lesionsD/DD/D

TETEPCNSL ( IRIS)PCNSL ( IRIS)TB( no CSF lymphocyte pleocytosis TB( no CSF lymphocyte pleocytosis

no extra neural manifestations)no extra neural manifestations)NeurocysticercosisNeurocysticercosisAbcessAbcess

►► Started on Toxoplasma treatment with Started on Toxoplasma treatment with BactrimBactrim 4 4 bdbd along with along with dexamethasone(23/05)dexamethasone(23/05)

►► Dramatic improvement for next two days Dramatic improvement for next two days patient insisting to go home Steroids were patient insisting to go home Steroids were being rapidly weaned off.being rapidly weaned off.

►► Deterioration again 26/05, headache Deterioration again 26/05, headache worsened, treated with NSAIDS.worsened, treated with NSAIDS.

►► Getting Getting drowzydrowzy, lethargic, , lethargic, pappiloedemapappiloedemapersisting. persisting.

►►Neurocysticercus ELISA Neurocysticercus ELISA –– negativenegative►►Toxoplasma serology _ negativeToxoplasma serology _ negative

Re L P done 28/05Re L P done 28/05Opening pressure 24Opening pressure 24No cellsNo cellsTP 1.12TP 1.12Glucose 1.82Glucose 1.82 (serum glucose (serum glucose 5.7)5.7)India ink India ink negneg, no organism, no organismToxo, Toxo, cysticercuscysticercus, VDRL, TB Culture & , VDRL, TB Culture & NurotrpicNurotrpic virus screen virus screen pendingpending

MRI BrainMRI Brain

Multiple ring enhancing lesions with some Multiple ring enhancing lesions with some meningeal enhancement adjacent to the meningeal enhancement adjacent to the lesions.lesions.

D/D D/D ToxoplasmosisToxoplasmosisTuberculosisTuberculosisPCNSL last optionPCNSL last option

►► Toxo treatment continuedToxo treatment continued►► Steroids tapered offSteroids tapered off►► Still decision was not to start TB treatment Still decision was not to start TB treatment

because of no clear evidencebecause of no clear evidence►► Neurological state was fluctuating. Neurological state was fluctuating.

Developed decrease level of consciousness Developed decrease level of consciousness on 1/06/08on 1/06/08

►► Started on TB treatment & so far she is Started on TB treatment & so far she is improving.improving.

HOW TO APPROACH RVD PATIENTS HOW TO APPROACH RVD PATIENTS WITH CNS MASS LESION & HEADACHEWITH CNS MASS LESION & HEADACHE

1)1) Degree of immune suppressionDegree of immune suppression

CD4 >500

CD4200-500

CD4<200

2) 2) RADIOLOGICAL APPEARANCERADIOLOGICAL APPEARANCE? Enhancement post contrast( inflamation)? Enhancement post contrast( inflamation)Steroids can convert enhancing to non Steroids can convert enhancing to non enhancing lesion.enhancing lesion.Two different categoriesTwo different categories

a) with mass effect ( TE, PCNSL, Abcess, a) with mass effect ( TE, PCNSL, Abcess, NCC, TB),NCC, TB),

b) without mass effect ( HIVE, CMV b) without mass effect ( HIVE, CMV encephalitis, PML).encephalitis, PML).

RADIOIMAGING AVAILABLERADIOIMAGING AVAILABLECT scanCT scanMRIMRISpecialized imaging studiesSpecialized imaging studies

Thalium 201 SPECT ScanThalium 201 SPECT ScanPET scanPET scanPerfusion MRIPerfusion MRIMR SpectroscopyMR Spectroscopy

Differentiate b/w PCNSL & infective lesion.Differentiate b/w PCNSL & infective lesion.

CT vs. MRICT vs. MRI40% lesion not picked by CT were 40% lesion not picked by CT were

diagnosed on MRI.diagnosed on MRI.3) 3) Further diagnostic approachFurther diagnostic approach

CSF analysisCSF analysisMC&SMC&SPCRPCRpositive EBV DNA in immunocompromised positive EBV DNA in immunocompromised

patients with finding suggestive of PCNSL patients with finding suggestive of PCNSL strongly support the diagnosis.strongly support the diagnosis.

CMV encephalitis Sensitivity 80%, Specificity CMV encephalitis Sensitivity 80%, Specificity 90%.90%.

TE sensitivity only 50% but specificity 96TE sensitivity only 50% but specificity 96--100%.100%.

Toxo seronegative patients with mass lesion, Toxo seronegative patients with mass lesion, probability of PCNSL is 0.74 which increases probability of PCNSL is 0.74 which increases if EBV is positive.if EBV is positive.

4) EMPIRIC THERAPY FOR TE4) EMPIRIC THERAPY FOR TEMultiple lesions radiologically consistent with either Multiple lesions radiologically consistent with either TE or PCNSL, in presence of positive TOXO TE or PCNSL, in presence of positive TOXO serology are likely to be TE,serology are likely to be TE,Likelihood of TE is much lower if patient is on TMP Likelihood of TE is much lower if patient is on TMP SMX prophylaxis.SMX prophylaxis.TOXO seronegatives, PCNSL is likely specially if TOXO seronegatives, PCNSL is likely specially if lesion is solitary or >4cm in diameter.lesion is solitary or >4cm in diameter.Clinical improvement in 1Clinical improvement in 1--2 weeks & radiological 2 weeks & radiological improvement in 2 weeks with regression of size improvement in 2 weeks with regression of size establishes TE as diagnosisestablishes TE as diagnosis

No response to treatmentNo response to treatment-- brain biopsy.brain biopsy.Steroids can cause false negative scan Steroids can cause false negative scan result.result.

5) 5) BRAIN BIOPSYBRAIN BIOPSYStereotactic brain biopsy( gold standard for Stereotactic brain biopsy( gold standard for

CNS mass lesion in AIDS)CNS mass lesion in AIDS)Definite diagnosis can be reached in 93Definite diagnosis can be reached in 93--

96% cases.96% cases.

Evidence of ex neural TB

NOYES

Treat TOXOTreat TB

Treatment response2/52

no yes

continue

CT/MRI

Multiloculated ring enhancing

Dense homogenous lesionsCorpus callosum, periventricular

LP safeLP unsafeSPECT,DWI,MRS

EBV IgM PCR

negativeBIOPSY positive

CNS Lymphoma Refer hematology

Cellularity, membraneTurn over

Low High

TB/TOXO treatment