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Does CD4 Cell Count Influence Computed Does CD4 Cell Count Influence Computed Tomography (CT) scan imaging features of Tomography (CT) scan imaging features of Intracranial Opportunistic Infections (OI) lesions Intracranial Opportunistic Infections (OI) lesions in adult HIV/ AIDS patients? in adult HIV/ AIDS patients?

Abdul Kareem M*,Abdul Kareem M*, siti jusna * Arif Abas** Mahiran Mustapha** AAhmad Munawir ***

• AP, Department of Radiology, School of Health Sciences, Universiti Sains AP, Department of Radiology, School of Health Sciences, Universiti Sains MalaysiaMalaysia, 16150- Kubang Kerian, Kota Bharu, Kelantan, Malaysia, 16150- Kubang Kerian, Kota Bharu, Kelantan, Malaysia

•

** HOD,Hospital Raja Perempuan Zainab II(HRPZ II) Kota Bharu, ** HOD,Hospital Raja Perempuan Zainab II(HRPZ II) Kota Bharu, Kelantan, Malaysia.Kelantan, Malaysia.

• Neurosciences, School of Medical Sciences, Universiti Sains Malaysia,Neurosciences, School of Medical Sciences, Universiti Sains Malaysia,• Kelantan.Kelantan.

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"People have been terrorised by these CD4 T-cell counts,” (ack)

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MechanismMechanism The CD4+ T-lymphocyte is the primary target for HIV. because of The CD4+ T-lymphocyte is the primary target for HIV. because of

the affinity of the virus for the CD4 surface marker.the affinity of the virus for the CD4 surface marker.

In HIV infection, CD4+ T cells are infected and they present In HIV infection, CD4+ T cells are infected and they present viral proteins and then are lysed by cytotoxic cells such as CD8+ viral proteins and then are lysed by cytotoxic cells such as CD8+ T lymphocytes T lymphocytes

As more and more CD4+ T cells are destroyed, the number of As more and more CD4+ T cells are destroyed, the number of CD4+ T-lymphocytes decreases, immune function falls and the CD4+ T-lymphocytes decreases, immune function falls and the risk and severity of opportunistic illnesses increase. risk and severity of opportunistic illnesses increase.

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NormalNormal CD4 counts : 500 – 1600/CD4 counts : 500 – 1600/µµll CD8 counts are between 375 and 1100. CD8 counts are between 375 and 1100. The ratio of CD4 cells to CD8The ratio of CD4 cells to CD8 0.9 - 1.9 . 0.9 - 1.9 . CD4 percentage is 20% - 40%. refers to total CD4 percentage is 20% - 40%. refers to total

lymphocytes. more stable-lymphocytes. more stable- A CD4% < 14% is a sign of AIDS in HIV A CD4% < 14% is a sign of AIDS in HIV

infection.infection.

WHAT ARE CD4 CELLS?WHAT ARE CD4 CELLS?

CD4 / T-4 cells / T-lymphocytes/ T "helper" cells are a type of lymphocyte (WBC) with CD4 molecules specific proteins on its surface.

It leads the attack against infections.

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IMPORTANCE OF THIS IMPORTANCE OF THIS STUDYSTUDY

2006: 4.3 million newly infected2006: 4.3 million newly infected with HIV with HIV > 95%> 95% of these are in low and middle income countries.. of these are in low and middle income countries.. 14,000/day become newly infected with HIV.14,000/day become newly infected with HIV. Of these, Of these, half are womenhalf are women and and 40% are young people (15-40% are young people (15-24 years old).24 years old).

Of the estimated Of the estimated 37 million adults HIV worldwide37 million adults HIV worldwide 7.2 m pts in SEA. 7.2 m pts in SEA. AIDS is now a leading cause of death worldwideAIDS is now a leading cause of death worldwide 630,000 died in 2006 630,000 died in 2006 3.1M DEATHS IN CHILDREN3.1M DEATHS IN CHILDREN

Kelantan recorded the highest numberKelantan recorded the highest number(596) of HIV/AIDS. As one-third of AIDS (596) of HIV/AIDS. As one-third of AIDS patients develop neurological complications, patients develop neurological complications, this study focuses on cranial CT features and this study focuses on cranial CT features and its association with CD4 count. its association with CD4 count.

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Aims and ObjectivesAims and Objectives

General ObjectivesGeneral Objectives1. To categorise HIV patients basing

CD4 count 2. To study CT scan features of

intracranial Opportunistic infections(OI) in HIV

patients

Specific ObjectiveSpecific ObjectiveTo assess the relationship between

cranial CT scanfindings intracranial Opportunistic

infections(OI) and CD4 count in HIV patients

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There is no correlation/ relationship between cranial CT scan findings of intracranial Opportunistic infections(OI) and CD4 count in HIV patients

Null HypothesisNull Hypothesis

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MethodologyMethodology: : Inclusion CriteriaInclusion Criteria 12 years old 12 years old and aboveand above HIV/AIDS patient with neurological HIV/AIDS patient with neurological

symptoms symptoms All patients who had cranial NECT and All patients who had cranial NECT and

CECT.CECT. All patients who had All patients who had CD4 count done within CD4 count done within

1 month 1 month of CT scan examination.of CT scan examination.Exclusion CriteriaExclusion Criteria HIV/AIDS patients whose cranial CT was HIV/AIDS patients whose cranial CT was

for for trauma trauma related neurological complaintsrelated neurological complaints HIV/AIDS patient undergone cranial CT HIV/AIDS patient undergone cranial CT

scan but without CD4 countscan but without CD4 count 4. HIV/AIDS patient had undergone only 4. HIV/AIDS patient had undergone only

cranial NECT scan cranial NECT scan

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Methodology: Methodology: TechniqueTechnique 1. Patient fasted for 4-6 hr 2. steroid cover if H/O allergy, asthma 3. Removal of metal objects (eg.earring, hair

pin) 4. CT: Axial Images from skull base to vertex 5. NCCT and 6. CECT: 50 ml of non-ionic I.V.CM was used Total number of patients needed: 56Total number of patients needed: 56Site: Site: IIn Hospital Raja Perempuan Zainab II (HRPZ II) and n Hospital Raja Perempuan Zainab II (HRPZ II) and

HUSMHUSM

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. Below are the technical parametn this study:

Patient position Supine

Area of interest/study From foramen magnum to the skull vertex

Gantry tilt 10 degree caudad angulation to the occipitomeatal baseline (OMBL) to reduce exposure to the lenses Range 1: base of foramen magnum to pituitary fossa (Slice thickness of 4.0mm) Range 2: pituitary fossa to cover the entire cerebrum (Slice thickness of 8.0mm)

X-ray tube voltage (kV) 120-140

Tube current (mAs) 220-260

Pitch 1.5

Algorithm Volume artifact reduction (VAR)

Kernel AH 40

Increment 2

Feed 3

Direction Caudo-cranial

Delay Start scan at the end of contrast injection

Methodology: Technique

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Blood test: confirmation of Blood test: confirmation of HIVHIV and and OI OI ((Cryptococcosis & Toxoplasmosis)Cryptococcosis & Toxoplasmosis)

ELISA (enzyme-linked immunosorbent assay) test or EIA ELISA (enzyme-linked immunosorbent assay) test or EIA test ( enzyme immunoassay) done for HIV screening.test ( enzyme immunoassay) done for HIV screening.

Partial Agglutination / Western-blot test for confirmation Partial Agglutination / Western-blot test for confirmation using Gene Laboratory Kit. using Gene Laboratory Kit.

43 blood samples for detection of Cryptococcal antigen. 43 blood samples for detection of Cryptococcal antigen. Out of 43, ten were positive.(about 20%) All are late stage Out of 43, ten were positive.(about 20%) All are late stage HIV.HIV.

Latex agglutination test using Murex Kit was used for Latex agglutination test using Murex Kit was used for detection of serum cryptococcal antigendetection of serum cryptococcal antigen

CD4 count estimation-CD4 count estimation- At HRPZ II- done by Immunocytometry System using Facs At HRPZ II- done by Immunocytometry System using Facs

Count Count ™™ Test, SEM-001 Test, SEM-001 Becton Dickinson Machine.Becton Dickinson Machine. At HUSM- done using direct immuno-assayAt HUSM- done using direct immuno-assay technique technique

using Facs Calibre Machine. using Facs Calibre Machine.

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Result: Result: Demographic featuresDemographic features

Among 56 patients: Among 56 patients: 48 48 males (85.7%)males (85.7%) 8 females (14.3%).8 females (14.3%). Malays =53Malays =53 (94.6 %) (94.6 %) Chinese = 3 ( 5.4% )Chinese = 3 ( 5.4% ) Mostly in fourth decade Mostly in fourth decade

(55.36%). (55.36%). youngest 22 year old youngest 22 year old eldest was 66 year old.eldest was 66 year old. mean age 34.25 yearsmean age 34.25 years standard deviation < 7.3 standard deviation < 7.3 20 30 40 50 60 70

age

0

5

10

15

20

Freq

uenc

y

Mean = 34.25Std. Dev. = 7.317N = 56

Histogram

Age distribution

** All the male patients in this study were intravenous drug users (whether active or former drug addict).

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StageStage CD4 count (cells/µl)CD4 count (cells/µl) No of patientNo of patient

EarlyEarly ≥ ≥ 500500 NilNil

MiddleMiddle 200 - 499200 - 499 77

LateLate ≤ ≤ 200200 4949

87.5% in the late stage of disease87.5% in the late stage of disease 41 patients have CD4 < 50cells/µl 41 patients have CD4 < 50cells/µl (73.2%) (73.2%) CD4: minimum - 1 maximum -452cells/µl. (mean57.8) CD4: minimum - 1 maximum -452cells/µl. (mean57.8) standard deviation less than 99.8. standard deviation less than 99.8.

** None in their early stage of illness.

Objective N0 – 1: To categorise HIV patients basing CD4 count

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<50

50-99

100-199

200-299

300-399

400-499

cd4subcategory

Pies show counts

73.21%n=41

12.50%n=7

1.79%n=1

5.36%n=3

1.79%n=1

5.36%n=3

CD4 subcategory

<50

50-99

100-199

200-299

300-399

400-499

cd4subcategory

Pies show counts

73.21%n=41

12.50%n=7

1.79%n=1

5.36%n=3

1.79%n=1

5.36%n=3

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Opportunistic organisms.Opportunistic organisms.

Positive sample for Toxoplasmosis 29 /41 Positive for Positive for Cryptococcosis 10/Cryptococcosis 10/43 43 Mixed infections: 17 Mixed infections: 17 patients (30.4%) patients (30.4%)

hadhad 9 patients with tuberculosis were positive for 9 patients with tuberculosis were positive for

toxoplasma, 4 patients + both for toxoplasma, 4 patients + both for toxoplasma and cryptococcus,toxoplasma and cryptococcus,

2 patients had cryptococcus with 2 patients had cryptococcus with tuberculosis tuberculosis

another 2 patients toxoplasma, another 2 patients toxoplasma, cryptococcus and TBcryptococcus and TB

Result:

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Morphology of CT lesion Toxoplasma antibody positive (n=29)

Cryptococcal antibody positive (n=10)

Ring-enhancing lesion 9 2

Nodular lesion 3 2

White matter hypodensity i.focal ii.multifocal

19

415

5

14

Diffuse cerebral edema 12 4

Hydrocephalus 1 1

Meningeal enhancement 9 2

Normal scan 77 3

Multiple lesions 20 3

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: Meningeal enhancement : Meningeal enhancement with white matter edemawith white matter edema

CM form predominatesCM form predominates Negative CT doesn’t Negative CT doesn’t

exclude CMexclude CM Best seen on MRIBest seen on MRI Usually involve sylvian Usually involve sylvian

F & Basal ganglia F & Basal ganglia Serum cryptococ Serum cryptococ

antigen is + in >99% antigen is + in >99% of AIDS related CM.of AIDS related CM.

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Nodular lesion Nodular lesion

Single Multiple

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Ring lesionRing lesion

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White matter edemaWhite matter edema

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Cerebral atrophyHydrocephalus- 1 (mild)

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The cerebrumThe cerebrum was significantly affected in 60.0%. was significantly affected in 60.0%. involve the parietal (40.0%), involve the parietal (40.0%), occipital (30.0%), occipital (30.0%), frontal (0%) andfrontal (0%) and temporal (10.0%) lobes. temporal (10.0%) lobes. Basal gangliaBasal ganglia and thalamus and thalamus only in 10.0% only in 10.0% MidbrainMidbrain in 20.0% in 20.0% cerebellum in 0.0% . cerebellum in 0.0% . Multiple lesions were:30%Multiple lesions were:30%

No significant correlation observed between No significant correlation observed between cryptococcosis with various site of intracranial lesion in with various site of intracranial lesion in this studythis study

Crypto: site of predilection: BG, Thalam & Midbr.Crypto: site of predilection: BG, Thalam & Midbr.

Association between cryptococcosis &site of intracranial lesion in our study

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Site of lesion cryptococcus(n = 43) X2

p-value

Positive n=10(%) Negative n=33(%)

Cerebral hemisphere Present Absent

6 (60.0%)4 (40.0%)

20 (60.6%) 13 (39.4%)

0.001 (1) 0.973 b

Frontal lobe Present Absent

0 (0%)10 (100.0%)

12 (36.4%) 21 (63.6%)

5.044893 (1) 0.025 b

Parietal lobe Present Absent

4 (40.0%)6 (60.0%)

15 (45.5%)18 (54.5%)

0.093 (1) 0.761 b

Temporal lobe Present Absent

1 (10.0%)9 (90.0%)

6 (18.2%)27 (81.8%)

0.377 (1) 0.539 b

Occipital lobe Present Absent

3 (30.0%)7 (70.0%)

12 (36.4%)21 (63.6%)

0.137 (1) 0.711 b

Basal ganglia-thalamic lesions Present Absent

1 (10.0%)9 (90.0%)

12 (36,4%)21 (63.6%)

2.529 (1) 0.112 b

Cerebellum Present Absent

0 (0.0%)10 (100.0%)

1 (3.0%)32 (97.0%)

- 1.000a

Brainstem (midbrain) Present AbsentMultiple lesions Present Absent

2 (20.0%)8 (80.0%)

3 (30.0%) 7 (70.0%)

5(15.2%)28 (84.8%)

15 (45.5%)18 (54.50%)

0.0132 (1) -

0.716b

1.000a

0.638a

aFisher’s Exact Test bPearson Chi-square Test

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Association between clinical stages with cryptococcal serology

Toxoplasma serology (n=43)

Clinical stage of disease Late stage Middle stage(CD4< 200cells/µl) (CD4 200-499cells/µl)

X2 (df)

p-value

Positive (n=10)

Negative (n=33)

10 (100.6%)

28 (84.8%)

0 (0%)

2 (15.2%)

_

0.320a

aFisher’s Exact Test

Association between Association between clinical stages of disease clinical stages of disease with Toxoplasma serologywith Toxoplasma serology

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Toxoplasma serology (n=41)

Clinical stage of disease Late stage Middle stage(CD4< 200cells/µl) (CD4 200-499cells/µl)

X2 (df)

p-value

Positive (n=29)

Negative (n=12)

28 (96.6%)

10 (83.3%)

1 (3.4%)

2 (16.7%)

_

0.200a

aFisher’s Exact Test

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Association of intracranial lesions to CD4 count

Intracranial lesion

Late stage CD4< 200cells/µl (%)

Middle stage CD4 200-499cells/µl (%)

X2 (df) p-value

Focal lesion Present Absent

71.4% 28.6%

42.9%57.1%

- 0.195a

Atrophy Present Absent

22.4%77.6%

14.3%85.7%

0.242(1) 0.622 b

Combination Present Absent

12.2%87.8%

14.3%85.7%

0.023(1) 0.879 b

aFisher’s Exact TestbPearson Chi-square Test

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ConclusionConclusion

None of the patient was in their None of the patient was in their early stage HIV.early stage HIV.

100% of cryptococcus pts were in 100% of cryptococcus pts were in late stagelate stage

The CD4 count ranges: 1 - The CD4 count ranges: 1 - 452cells/452cells/µµl. l.

The mean count was 57.8.The mean count was 57.8. CD4 count was very much helpful in CD4 count was very much helpful in

predicting the stage of HIV and predicting the stage of HIV and causative organisms.causative organisms.

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1. 1. Interhospital transferInterhospital transfer –CT films were given away to –CT films were given away to the district hospital when patients were transferred. No the district hospital when patients were transferred. No PACS inGHPACS inGH

Untraceable CT filmsUntraceable CT films – No proper recording system. – No proper recording system. Many CT films are missing from infectious disease Many CT films are missing from infectious disease clinic or radiology department storage room at HRPZ II.clinic or radiology department storage room at HRPZ II.

Co-infection Co-infection of multiple opportunistic infections – of multiple opportunistic infections – presence of other multiple opportunistic infections in a presence of other multiple opportunistic infections in a given patient giving rise to atypical or non-specific CT given patient giving rise to atypical or non-specific CT findings. findings.

Imaging modalityImaging modality – CT is known to have low sensitivity – CT is known to have low sensitivity in demonstrating the lesion as compared to MRI. This in demonstrating the lesion as compared to MRI. This factor for example, might affect the detection of ring factor for example, might affect the detection of ring lesion in this study. lesion in this study.

Problems and limitationsProblems and limitations

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Problems and limitationsProblems and limitations

CD4 count CD4 count ––measurement only be measurement only be performed on certain days. performed on certain days.

CT scan usually was performed on the CT scan usually was performed on the day of admission. day of admission.

Thus if CT scan was ordered within Thus if CT scan was ordered within that period, the that period, the CD4 count might be CD4 count might be beyond one month period of the scanbeyond one month period of the scan. .

While waiting, several newly diagnosed While waiting, several newly diagnosed patients diedpatients died before CD4 count was before CD4 count was performed performed

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RecommendationsRecommendations

Severe immunosuppression in HIV/AIDS predisposed the Severe immunosuppression in HIV/AIDS predisposed the patients to multiple types of infections. The purpose of this patients to multiple types of infections. The purpose of this study is to simply predict the intracranial sites commonly study is to simply predict the intracranial sites commonly involved in HIV/AIDS patients. However, since multiple cerebral involved in HIV/AIDS patients. However, since multiple cerebral infections can co-exist at a given time, the CT scan findings infections can co-exist at a given time, the CT scan findings varied enormously. varied enormously.

We suggest the following;We suggest the following;

Another study to be carried out with Another study to be carried out with larger sample sizelarger sample size.. Written guidelines should be provided to the physician so that Written guidelines should be provided to the physician so that

consistent history taking, physical examination and consistent history taking, physical examination and Base line Base line laboratory resultslaboratory results of the patients can be achieved. of the patients can be achieved.

Further characterizationFurther characterization of suspicious lesions should be done of suspicious lesions should be done using MRIusing MRI

Biopsy of lesion should be considered if the laboratory and Biopsy of lesion should be considered if the laboratory and imaging findings are inconclusive. imaging findings are inconclusive.

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ReferencesReferences1.1. Alexander, S., Mark, Atlas, S., W., (1989). Progressive Multifocal Leukoencephalopathy in Patients with AIDS: Alexander, S., Mark, Atlas, S., W., (1989). Progressive Multifocal Leukoencephalopathy in Patients with AIDS:

Appearance on MR Images.Neuroradiology, 173:517-520.Appearance on MR Images.Neuroradiology, 173:517-520.2.2. AIDS Epidemic Update, December (2005).AIDS Epidemic Update, December (2005).3.3. Ackermann, H-W., Bertiaume, L., Tremblay, M.,(2001) Viral Pathogens in Diagrams. CRC Press.Ackermann, H-W., Bertiaume, L., Tremblay, M.,(2001) Viral Pathogens in Diagrams. CRC Press.4.4. Balakrishnan, J., Becker,P., S., Kumar, A., J., Zinreich, S., J., McArthur,J., C., Bryan, R., N.,(1990).Acquired Balakrishnan, J., Becker,P., S., Kumar, A., J., Zinreich, S., J., McArthur,J., C., Bryan, R., N.,(1990).Acquired

Immunodeficiency Syndrome: Correlation of Radiologic and Pathologic Findings in the Brain. Radiographics, 10:201-Immunodeficiency Syndrome: Correlation of Radiologic and Pathologic Findings in the Brain. Radiographics, 10:201-215. 215.

5.5. Barber,C., J., Rowlands, P., C., McCarty, M., Choudhri, H., Stevens, J., M.,(1990). Clinical Utility of Cranial CT in HIV Barber,C., J., Rowlands, P., C., McCarty, M., Choudhri, H., Stevens, J., M.,(1990). Clinical Utility of Cranial CT in HIV Positive and AIDS Patients with Neurological Disease. Clinical Radiology, 42:164-165.Positive and AIDS Patients with Neurological Disease. Clinical Radiology, 42:164-165.

6.6. Belman,A.,L.,(2002) HIV-1 infection and AIDS, Neurologic Clinics.Volume 20, Number 4,W.B.Saunders Company.Belman,A.,L.,(2002) HIV-1 infection and AIDS, Neurologic Clinics.Volume 20, Number 4,W.B.Saunders Company.7.7. Cohen .P., T.( 1996). The AIDSs Knowledge Based Textbook, Second Edition, Little Brown.Cohen .P., T.( 1996). The AIDSs Knowledge Based Textbook, Second Edition, Little Brown.8.8. Connor, M.,D., Lammie, G., A., Bell, J., E., Warlow, C., P., Simmonds, P., Brettle, R., D.(2003) Cerebral Infarction in Adult Connor, M.,D., Lammie, G., A., Bell, J., E., Warlow, C., P., Simmonds, P., Brettle, R., D.(2003) Cerebral Infarction in Adult

AIDS patients: Observations From the Edinburgh HIV Autopsy Cohort. Stroke, 31:2117-2126.AIDS patients: Observations From the Edinburgh HIV Autopsy Cohort. Stroke, 31:2117-2126.9.9. Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A (2003). AIDS-Related Opportunistic Infections in Hospital Kuala Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A (2003). AIDS-Related Opportunistic Infections in Hospital Kuala

Lumpur. Jpn.J.Infect.Dis., 56.187-192.Lumpur. Jpn.J.Infect.Dis., 56.187-192.10.10. Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A.,Leong .C. L, Mahmud. R. (2004). Toxoplasmosis in HIV/AIDS Patients: Nissapatorn. V, Lee. C, Fatt. Q.K., Abdullah. K.A.,Leong .C. L, Mahmud. R. (2004). Toxoplasmosis in HIV/AIDS Patients:

Current Situation. Jpn.J.Infect.Dis., 57.160-165.Current Situation. Jpn.J.Infect.Dis., 57.160-165.11.11. Nissapatorn. V, Lee. C, Abdullah. Nissapatorn. V, Lee. C, Abdullah. K.A., Mahmud. R. (2004). Spectrum of opportunistic infections among HIV-infected K.A., Mahmud. R. (2004). Spectrum of opportunistic infections among HIV-infected

patients in Malaysia. Southeast Asian J Trop Med Public Health. 35:26-32.patients in Malaysia. Southeast Asian J Trop Med Public Health. 35:26-32.12.12. Mohamad Z., Naing N.N.(2004). Characteristic of HIV-infected tuberculosis patients in Kota Bharu Hospital, Kelantan Mohamad Z., Naing N.N.(2004). Characteristic of HIV-infected tuberculosis patients in Kota Bharu Hospital, Kelantan

from 1998 to 2001. Southeast Asian J Trop Med Public Health. 35:140-3..from 1998 to 2001. Southeast Asian J Trop Med Public Health. 35:140-3..13.13. Nissapatorn. V, Lee. C, Ithol. I, Yik. F.M., Abdullah. K. A. (2003). Tuberculosis In AIDS Patients. Malaysia Journal of Nissapatorn. V, Lee. C, Ithol. I, Yik. F.M., Abdullah. K. A. (2003). Tuberculosis In AIDS Patients. Malaysia Journal of

Medical Sciences, Vol 10, No 1:60-64.Medical Sciences, Vol 10, No 1:60-64.14.14. Federle, M., P, (1988) A Radiologist Looks at Aids: Imaging Evaluation Based on Symptom Complexes.Radiology, Federle, M., P, (1988) A Radiologist Looks at Aids: Imaging Evaluation Based on Symptom Complexes.Radiology,

166:553-562.166:553-562.15.15. Cheong I., Lim. A.,Lee. C., Ibrahim. Z., Sarvanathan.K.(1997). Epidemiology and clinical characteristics of HIV-infected Cheong I., Lim. A.,Lee. C., Ibrahim. Z., Sarvanathan.K.(1997). Epidemiology and clinical characteristics of HIV-infected

patients in Kuala Lumpur. Med J Malaysia. 52:313-7.patients in Kuala Lumpur. Med J Malaysia. 52:313-7.16.16. Ismail.R., Doi. S., Naganathna. N (1995). HIV infection in Malaysia: a report of cases at the University Hospital, Kuala Ismail.R., Doi. S., Naganathna. N (1995). HIV infection in Malaysia: a report of cases at the University Hospital, Kuala

Lumpur. Med J Malaysia. 50:298-301.Lumpur. Med J Malaysia. 50:298-301.17.17. of Central Nervous System Infections. Seminar in Roentgenology, VolXXXIV, No 2 (April): 123-143.of Central Nervous System Infections. Seminar in Roentgenology, VolXXXIV, No 2 (April): 123-143.18.18. Wig.N., Wali.J.P.(2000). Central Nervous System and HIV/AIDS. Journal of Indian Academy of Clinical Medicine.Vol 5; Wig.N., Wali.J.P.(2000). Central Nervous System and HIV/AIDS. Journal of Indian Academy of Clinical Medicine.Vol 5;

No 2:163-168.No 2:163-168.19.19. Stevens.D.A., Denning.D. W., Shatsky.s., Armstrong. R.W., Adler. J. D., Lewis.B.H.(1999). Cryptococcal meningitis in the Stevens.D.A., Denning.D. W., Shatsky.s., Armstrong. R.W., Adler. J. D., Lewis.B.H.(1999). Cryptococcal meningitis in the

immunocompromised host: intracranial hypertension and other complication. Mycopathologia.146:1-8.immunocompromised host: intracranial hypertension and other complication. Mycopathologia.146:1-8.20.20. ..

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ReferencesReferences20 Lorenzo. G.D., Pagano. M., Garau. M.L., Deri. N., Cahn.P., Perez.H., Pagano.M.A.20 Lorenzo. G.D., Pagano. M., Garau. M.L., Deri. N., Cahn.P., Perez.H., Pagano.M.A.21. (2005). Units of Neurology and Section of Infectious Diseases, Fernandez Hospital, Buemous Aires, Argentina. 21. (2005). Units of Neurology and Section of Infectious Diseases, Fernandez Hospital, Buemous Aires, Argentina.

Neuroimaging findings in cerebral toxoplasmosis (CT) in AIDS patients (Poster abstracts).Neuroimaging findings in cerebral toxoplasmosis (CT) in AIDS patients (Poster abstracts).22. Graham III, C., B., Wippold II, F., J., Pilgram, T., K., Fisher, E., J., Smoker, W., R., K.,(2000). Screening CT of the Brain 22. Graham III, C., B., Wippold II, F., J., Pilgram, T., K., Fisher, E., J., Smoker, W., R., K.,(2000). Screening CT of the Brain

Determined by CD4 Count in HIV-Positive Patients Presenting with Headache. AJNR Am J Neuroradiol, 21:451-454.Determined by CD4 Count in HIV-Positive Patients Presenting with Headache. AJNR Am J Neuroradiol, 21:451-454.23. Graham III, C.,B.,Wippold II, F., J.(2001) Headache in the HIV patient: A review with special attention to the role of 23. Graham III, C.,B.,Wippold II, F., J.(2001) Headache in the HIV patient: A review with special attention to the role of

imaging. Cephalalgia, 21:169-174.imaging. Cephalalgia, 21:169-174.24. Gilliams., A., R., Allen, E., Hrieb, K., Venna, N., Craven, D., Carter, A., P.,(1997) Cerebral Infarction in Patients with AIDS. 24. Gilliams., A., R., Allen, E., Hrieb, K., Venna, N., Craven, D., Carter, A., P.,(1997) Cerebral Infarction in Patients with AIDS.

AJNR Am J Neuroradiol, 18:1581-1585.AJNR Am J Neuroradiol, 18:1581-1585.25. Gifford, A., L., Frederick, M., Hecht,(2001). 25. Gifford, A., L., Frederick, M., Hecht,(2001). Evaluating HIV-infected Patients With Headache: Who Needs Computed Evaluating HIV-infected Patients With Headache: Who Needs Computed

Tomography?. Headache, 41:441-448. Tomography?. Headache, 41:441-448. 26. Schutte.C.M., (2001). Clinical Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-26. Schutte.C.M., (2001). Clinical Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-

Negative Patients with Tuberculous Meningitis. Infection, 29: 213-217.Negative Patients with Tuberculous Meningitis. Infection, 29: 213-217.27. Whiteman.M., Espinoza. L., Post. M.J.D., Bell. M. D., Falcone. S. (1995). Central Nervous system Tuberculosis in HIV-27. Whiteman.M., Espinoza. L., Post. M.J.D., Bell. M. D., Falcone. S. (1995). Central Nervous system Tuberculosis in HIV-

Infected Patients: Clinical and Radiographic Findings. Infected Patients: Clinical and Radiographic Findings. AJNR Am J Neuroradiol 16:1319-1327.AJNR Am J Neuroradiol 16:1319-1327.28. Thwaites. G.E., Hien. T. T. (2005). 28. Thwaites. G.E., Hien. T. T. (2005). Tuberculous meningitis:many question, too few answers. Tuberculous meningitis:many question, too few answers. Lancet Neuro. 4:160-70.Lancet Neuro. 4:160-70.29. Engin.G., Acunas. B., Acunas. B., Tunaci. M. (2000). 29. Engin.G., Acunas. B., Acunas. B., Tunaci. M. (2000). Imaging of Extrapulmonary Tuberculosis. Radiographics. 20:471-Imaging of Extrapulmonary Tuberculosis. Radiographics. 20:471-

488.488.30. Harisinghani.M.G., McLoud. T. c., Shepad.J.A.O., Ko.j.P., Shroff.M.M., Muller.P.R.(2000). Tuberculosis from Head to Toe. 30. Harisinghani.M.G., McLoud. T. c., Shepad.J.A.O., Ko.j.P., Shroff.M.M., Muller.P.R.(2000). Tuberculosis from Head to Toe.

Radiographics;20:449-470.Radiographics;20:449-470.31. Whelan.M.a., Stern. J. (1981). Intracranial Tuberculoma. Radiology 138:75-81.31. Whelan.M.a., Stern. J. (1981). Intracranial Tuberculoma. Radiology 138:75-81.32. Cornell.S.H., Jacoby. C.G. (1982). The varied Computed Tomographic Appearance of Intracranial Cryptococcosis. 32. Cornell.S.H., Jacoby. C.G. (1982). The varied Computed Tomographic Appearance of Intracranial Cryptococcosis.

Radiology.143:703-707.Radiology.143:703-707.33. Popovich. M. J., Arthur.R.H., Helmer. E. (1989). CT of Intracranial Cryptococcosis. AJR; 154 (March):603-606.33. Popovich. M. J., Arthur.R.H., Helmer. E. (1989). CT of Intracranial Cryptococcosis. AJR; 154 (March):603-606.34. Harrison. T. S (2000). 34. Harrison. T. S (2000). Cryptococcus neoformansCryptococcus neoformans and Cryptococcosis. Journal of Infection. 41:12-17. and Cryptococcosis. Journal of Infection. 41:12-17.35. Portocarrero.J.S., Cecilia. E. P. (1997). Intracerebral mass lesions in Patients eith Human Immunodeficiency Virus 35. Portocarrero.J.S., Cecilia. E. P. (1997). Intracerebral mass lesions in Patients eith Human Immunodeficiency Virus

Infection and Cryptococcal Meningitis. Case report. Diag Microbiol Infect Dis. 29:193-198.Infection and Cryptococcal Meningitis. Case report. Diag Microbiol Infect Dis. 29:193-198.36. Schwartzman.J.D. (2001). Toxoplasmosis. Principles and Practice of Clinical Parasitology. John Wiley & Sons Ltd.36. Schwartzman.J.D. (2001). Toxoplasmosis. Principles and Practice of Clinical Parasitology. John Wiley & Sons Ltd.37. Wong.J., Quint.d. J.(1999). Imaging37. Wong.J., Quint.d. J.(1999). Imaging

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Thank youThank you

Thank youThank you

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Pathogenesis in the brainPathogenesis in the brain Indeed, postmortem neuro-pathological series reveal that Indeed, postmortem neuro-pathological series reveal that

CNS abnormalities occur in up to 90% of patient with CNS abnormalities occur in up to 90% of patient with advanced AIDS (Connor et al, 2006). advanced AIDS (Connor et al, 2006).

Brain parenchyma Brain parenchyma CSF (and reverse) CSF (and reverse) Infection of Infection of stromal cells, macrophages, endothelial cell and choroids stromal cells, macrophages, endothelial cell and choroids

plexusplexus. ependymal & subependymal cells. ependymal & subependymal cells Damage to the nervous system via 3 Damage to the nervous system via 3

ways:ways: i. i. Direct infection/ killingDirect infection/ killing or alteration of or alteration of

cellular cellular metabolic function (cytopathic effects). The metabolic function (cytopathic effects). The retention of viral genome in neural cells in a persistent retention of viral genome in neural cells in a persistent latent formlatent form cell dysfunction. cell dysfunction.

ii. ii. cytotoxiccytotoxic action of HIV-specific products or aberrantly action of HIV-specific products or aberrantly secreted cellular products secreted cellular products

In addition, In addition, autoimmune mechanismsautoimmune mechanisms and such factors as and such factors as virus strain may also play a role in nervous system virus strain may also play a role in nervous system dysfunction.dysfunction.

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Clinical Variables Clinical Variables ::

A A •• Sex Sex –– male or female male or female B. B. AgeAge –– age recorded to the nearest year age recorded to the nearest year C. C. Neurological signs and symptomsNeurological signs and symptoms - - Signs - GCS, fever, neck stiffness and neurological Signs - GCS, fever, neck stiffness and neurological

findings.findings. Symptoms:-hemiplFocal:egia, hemiparesis, slurred Symptoms:-hemiplFocal:egia, hemiparesis, slurred

speech, CN palsy speech, CN palsy ii). Nonfocal symptoms-headache, seizure, ii). Nonfocal symptoms-headache, seizure,

abnormal behaviour, altered sensoriumabnormal behaviour, altered sensorium D D •• CD4 countCD4 count –– A/C to 1993 revised CDC classification A/C to 1993 revised CDC classification

systems,systems, Category 1 (early stage, CD4 ≥ 500cells/Category 1 (early stage, CD4 ≥ 500cells/µµl) , l) , category 2: (middle stage, CD4 200-499cells/category 2: (middle stage, CD4 200-499cells/µµl) and l) and category 3 (late stage, CD4 <2000cells/category 3 (late stage, CD4 <2000cells/µµl).l). E E •• CT brain findingsCT brain findings –– edema, ring-lesion, nodular lesion, edema, ring-lesion, nodular lesion, leptomeningeal enhancement, leptomeningeal enhancement,

atrophy.atrophy. FF•• Associated opportunistic or co-infection:Associated opportunistic or co-infection:

Toxoplasma gondii, Cryptococcus neoformansToxoplasma gondii, Cryptococcus neoformans, CMV, , CMV, Herpes virus, Hepatitis C and B viruses.Herpes virus, Hepatitis C and B viruses.

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Diagram of HIV & its protein Diagram of HIV & its protein locationslocations

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Clinical course of HIV Clinical course of HIV infectioninfection

HIV-1 Infection is associated with a HIV-1 Infection is associated with a progressive loss of CD4+ T-cells progressive loss of CD4+ T-cells

STAGES OF HIV/AIDS CD4+ T CELL COUNTSTAGES OF HIV/AIDS CD4+ T CELL COUNT

Early < 500 x 10 000 000/l Early < 500 x 10 000 000/l

Late < 200 x 10 000 000/l Late < 200 x 10 000 000/l

Advanced < 50 x 10 000 000/l Advanced < 50 x 10 000 000/l HIV plasma levels during all stages of infection HIV plasma levels during all stages of infection

range from just 50 to 11 million virions per ml. range from just 50 to 11 million virions per ml.

The rate of loss of CD4+ T-cells is linked with an The rate of loss of CD4+ T-cells is linked with an increase in viral load. increase in viral load.

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MethodologyMethodology

Sample size was calculated using Power and Sample software Where, P0 = proportion of presence of neurological symptoms in patient with positive scan = 0.373p1 = proportion of absence of neurological symptoms in patient with positive CT scan = 0.627α = 0.05 , m = 2 , = 80% = 0.8Thus, sample size (n) = 45 power To include twenty five percent (25%) drop-out:Number of cases: 45 + 11 = 56Total number of patients needed for the Total number of patients needed for the study is = 56.study is = 56.Site: ISite: In Hospital Raja Perempuan Zainab II (HRPZ II) and HUSM

Sample size Sample size calculationcalculation