The document examines the relationship between CD4 cell count and computed tomography (CT) scan findings of intracranial opportunistic infections in HIV/AIDS patients. It found that 87.5% of patients were in the late stage of disease with CD4 counts below 200 cells/μl. Common opportunistic infections seen on CT scans were Toxoplasmosis and Cryptococcosis. There was no significant correlation observed between Cryptococcosis and the site of intracranial lesions. Both Toxoplasmosis and Cryptococcosis serology were strongly associated with late stage disease.

1. Does CD4 Cell Count Influence Computed Tomography (CT)
scan imaging features of Intracranial Opportunistic Infections
(OI) lesions in adult HIV/ AIDS patients?
Abdul Kareem M*, siti jusna * Arif Abas** Mahiran Mustapha**
AAhmad Munawir ***
• AP, Department of Radiology, School of Health Sciences, Universiti Sains
Malaysia, 16150- Kubang Kerian, Kota Bharu, Kelantan, Malaysia
•
** HOD,Hospital Raja Perempuan Zainab II(HRPZ II) Kota Bharu,
Kelantan, Malaysia.
• Neurosciences, School of Medical Sciences, Universiti Sains Malaysia,
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• Kelantan.

2. "People have been terrorised by these CD4 T-
cell counts,” (ack)
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3.  The CD4+ T-lymphocyte is the primary target for HIV. because of the
affinity of the virus for the CD4 surface marker.
 In HIV infection, CD4+ T cells are infected and they present viral proteins
and then are lysed by cytotoxic cells such as CD8+ T lymphocytes
 As more and more CD4+ T cells are destroyed, the number of CD4+ T-
lymphocytes decreases, immune function falls and the risk and severity of
opportunistic illnesses increase.
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4. 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.
Normal
 CD4 counts : 500 – 1600/µl
 CD8 counts are between 375 and 1100.
 The ratio of CD4 cells to CD8 0.9 - 1.9 .
 CD4 percentage is 20% - 40%. refers to total
lymphocytes. more stable-
 A CD4% < 14% is a sign of AIDS in HIV infection.
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5.  2006: 4.3 million newly infected with HIV
 > 95% of these are in low and middle income countries..
 14,000/day become newly infected with HIV.
 Of these, half are women and 40% are young people
(15-24 years old).
 Of the estimated 37 million adults HIV worldwide
 7.2 m pts in SEA.
 AIDS is now a leading cause of death worldwide
 630,000 died in 2006
 3.1M DEATHS IN CHILDREN
 Kelantan recorded the highest number
(596) of HIV/AIDS. As one-third of AIDS
patients develop neurological complications,
this study focuses on cranial CT features and
its association with CD4 count.
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6. Aims and Objectives
General Objectives
1. To categorise HIV patients basing CD4 count
2. To study CT scan features of intracranial
Opportunistic infections(OI) in HIV patients
Specific Objective
To assess the relationship between cranial CT scan
findings intracranial Opportunistic infections(OI)
and CD4 count in HIV patients
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7. Null Hypothesis
There is no correlation/ relationship
between cranial CT scan findings of
intracranial Opportunistic infections(OI)
and CD4 count in HIV patients
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8. Methodology: Inclusion Criteria
 12 years old and above
 HIV/AIDS patient with neurological symptoms
 All patients who had cranial NECT and CECT.
 All patients who had CD4 count done within 1 month
of CT scan examination.
Exclusion Criteria
 HIV/AIDS patients whose cranial CT was for trauma
related neurological complaints
 HIV/AIDS patient undergone cranial CT scan but
without CD4 count
 4. HIV/AIDS patient had undergone only cranial
NECT scan
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9. Methodology: Technique
 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: 56
Site: In Hospital Raja Perempuan Zainab II (HRPZ
II) and HUSM
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10. Methodology: Technique
. Below are the technical parametn this study:
Supine
Patient position
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
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11. Blood test: confirmation of HIV and OI
(Cryptococcosis & Toxoplasmosis)
 ELISA (enzyme-linked immunosorbent assay) test or EIA test ( enzyme
immunoassay) done for HIV screening.
 Partial Agglutination / Western-blot test for confirmation using Gene
Laboratory Kit.
 43 blood samples for detection of Cryptococcal antigen. Out of 43, ten were
positive.(about 20%) All are late stage HIV.
 Latex agglutination test using Murex Kit was used for detection of serum
cryptococcal antigen
CD4 count estimation-
 At HRPZ II- done by Immunocytometry System using Facs Count ™ Test,
SEM-001
 Becton Dickinson Machine.
 At HUSM- done using direct immuno-assay technique using Facs Calibre
Machine.
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12. Result: Demographic features
Histogram
20
 Among 56 patients:
 48 males (85.7%)
15  8 females (14.3%).
 Malays =53 (94.6 %)
Frequency
 Chinese = 3 ( 5.4% )
10
 Mostly in fourth decade (55.36%).
 youngest 22 year old
5  eldest was 66 year old.
 mean age 34.25 years
Mean = 34.25
0
Std. Dev. = 7.317
N = 56
 standard deviation < 7.3
20 30 40 50 60 70
age
Age distribution
** All the male patients in this study were intravenous drug users
(whether active or former drug addict).
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13. Objective N0 – 1: To categorise HIV patients basing CD4 count
Stage CD4 count (cells/µl) No of patient
Early ≥ 500 Nil
Middle 200 - 499 7
Late ≤ 200
49
87.5% in the late stage of disease
41 patients have CD4 < 50cells/µl (73.2%)
CD4: minimum - 1 maximum -452cells/µl. (mean57.8)
standard deviation less than 99.8.
** None in their early stage of illness.
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14. 5.36%
1.79% n=3
n=1
5.36%
n=3
1.79%
n=1 cd4subca tegory
<50
50-99
100-199
12.50% 200-299
n=7 300-399
400-499
Pies show counts
73.21%
n=41
cd4subca tegory
<50
50-99
100-199
200-299
300-399 CD4 subcategory
400-499
Pies show counts
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%

15. Result:
Opportunistic organisms.
 Positive sample for Toxoplasmosis 29 /41
 Positive for Cryptococcosis 10/43
 Mixed infections: 17 patients (30.4%) had
 9 patients with tuberculosis were positive for
toxoplasma, 4 patients + both for toxoplasma
and cryptococcus,
 2 patients had cryptococcus with tuberculosis
 another 2 patients toxoplasma, cryptococcus
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16. Morphology of CT lesion Toxoplasma antibody Cryptococcal
positive (n=29) antibody
positive (n=10)
Ring-enhancing lesion 9 2
Nodular lesion 3 2
White matter 19 5
hypodensity
i.focal 4 1
ii.multifocal 15 4
Diffuse cerebral edema 12 4
Hydrocephalus 1 1
Meningeal enhancement 9 2
Normal scan 7 3
Multiple lesions 20 3
Morphology of CT lesion
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17. : Meningeal enhancement with white
matter edema
 CM form predominates
 Negative CT doesn’t exclude
CM
 Best seen on MRI
 Usually involve sylvian F &
Basal ganglia
 Serum cryptococ antigen is +
in >99% of AIDS related CM.
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18. Nodular lesion
Single Multiple
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19. (c) mkareem 19

20. Ring lesion
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21. White matter edema
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22. Cerebral atrophy
Hydrocephalus- 1 (mild)
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23. Association between cryptococcosis &
site of intracranial lesion in our study
 The cerebrum was significantly affected in 60.0%.
involve the parietal (40.0%),
occipital (30.0%),
frontal (0%) and
temporal (10.0%) lobes.
 Basal ganglia and thalamus only in 10.0%
 Midbrain in 20.0%
 cerebellum in 0.0% .
 Multiple lesions were:30%
 No significant correlation observed between cryptococcosis with various
site of intracranial lesion in this study
 Crypto: site of predilection: BG, Thalam & Midbr.
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24. Site of lesion cryptococcus(n = 43) p-value
X2
Positive n=10(%) Negative n=33(%)
Cerebral hemisphere 20 (60.6%) 0.001 (1) 0.973 b
Present 6 (60.0%) 13 (39.4%)
Absent 4 (40.0%)
Frontal lobe 12 (36.4%) 5.044893 (1) 0.025 b
Present 0 (0%) 21 (63.6%)
Absent 10 (100.0%)
Parietal lobe 15 (45.5%) 0.093 (1) 0.761 b
Present 4 (40.0%) 18 (54.5%)
Absent 6 (60.0%)
Temporal lobe 6 (18.2%) 0.377 (1) 0.539 b
Present 1 (10.0%) 27 (81.8%)
Absent 9 (90.0%)
Occipital lobe Present 3 (30.0%) 12 (36.4%) 0.137 (1) 0.711 b
Absent 7 (70.0%) 21 (63.6%)
Basal ganglia-thalamic 12 (36,4%) 2.529 (1) 0.112 b
lesions Present 1 (10.0%) 21 (63.6%)
Absent 9 (90.0%)
Cerebellum Present 0 (0.0%) 1 (3.0%) - 1.000a
Absent 10 (100.0%) 32 (97.0%)
Brainstem (midbrain) 0.0132 (1) 0.716b
Present 2 (20.0%) 5(15.2%) - 1.000a
Absent 8 (80.0%) 28 (84.8%)
Multiple lesions
Present 3 (30.0%) 15 (45.5%) 0.638a
Absent 7 (70.0%) 18 (54.50%)
a
Fisher’s Exact Test (c) mkareem 24
b
Pearson Chi-square Test

25. Association between clinical stages with cryptococcal serology
Clinical stage of disease
Toxoplasma serology Late stage Middle stage
(n=43) (CD4< 200cells/µl) (CD4 200-499cells/µl) X2 (df) p-value
_
Positive (n=10) 10 (100.6%) 0 (0%)
0.320a
Negative (n=33) 28 (84.8%) 2 (15.2%)
a
Fisher’s Exact Test
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26. Association between clinical stages
of disease with Toxoplasma serology
Clinical stage of disease
Toxoplasma serology Late stage Middle stage
(n=41) (CD4< 200cells/µl) (CD4 200-499cells/µl) X2 (df) p-value
_
Positive (n=29) 28 (96.6%) 1 (3.4%)
0.200a
Negative (n=12) 10 (83.3%) 2 (16.7%)
a
Fisher’s Exact Test
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27. Association of intracranial lesions to CD4 count
Intracranial Late stage Middle stage X2 (df) p-value
lesion CD4< 200cells/µl CD4 200-499cells/µl
(%) (%)
Focal lesion - 0.195a
Present 71.4% 42.9%
Absent 28.6% 57.1%
Atrophy 0.242(1) 0.622 b
Present 22.4% 14.3%
Absent 77.6% 85.7%
Combination 0.023(1) 0.879 b
Present 12.2% 14.3%
Absent 87.8% 85.7%
a
Fisher’s Exact Test
b
Pearson Chi-square Test
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28. Conclusion
 None of the patient was in their early stage HIV.
 100% of cryptococcus pts were in late stage
 The CD4 count ranges: 1 - 452cells/µl.
 The mean count was 57.8.
 CD4 count was very much helpful in predicting
the stage of HIV and causative organisms.
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29. Problems and limitations
 1. Interhospital transfer –CT films were given away to
the district hospital when patients were transferred. No
PACS inGH
 Untraceable CT films – No proper recording system.
Many CT films are missing from infectious disease
clinic or radiology department storage room at HRPZ II.
 Co-infection of multiple opportunistic infections –
presence of other multiple opportunistic infections in a
given patient giving rise to atypical or non-specific CT
findings.
 Imaging modality – CT is known to have low sensitivity
in demonstrating the lesion as compared to MRI. This
factor for example, might affect the detection of ring
lesion in this study.
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30. Problems and limitations
 CD4 count –measurement only be performed
on certain days.
 CT scan usually was performed on the day of
admission.
 Thus if CT scan was ordered within that period,
the CD4 count might be beyond one month
period of the scan.
 While waiting, several newly diagnosed patients
died before CD4 count was performed
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31. Recommendations

Severe immunosuppression in HIV/AIDS predisposed the
patients to multiple types of infections. The purpose of this
study is to simply predict the intracranial sites commonly
involved in HIV/AIDS patients. However, since multiple cerebral
infections can co-exist at a given time, the CT scan findings
varied enormously.
We suggest the following;
 Another study to be carried out with larger sample size.
 Written guidelines should be provided to the physician so that
consistent history taking, physical examination and Base line
laboratory results of the patients can be achieved.
 Further characterization of suspicious lesions should be done
using MRI
 Biopsy of lesion should be considered if the laboratory and
imaging findings are inconclusive.
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32. References
1. Alexander, S., Mark, Atlas, S., W., (1989). Progressive Multifocal Leukoencephalopathy in Patients with AIDS: Appearance on MR Images.Neuroradiology,
173:517-520.
2. AIDS Epidemic Update, December (2005).
3. Ackermann, H-W., Bertiaume, L., Tremblay, M.,(2001) Viral Pathogens in Diagrams. CRC Press.
4. 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, 10:201-215.
5. 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.
6. Belman,A.,L.,(2002) HIV-1 infection and AIDS, Neurologic Clinics.Volume 20, Number 4,W.B.Saunders Company.
7. Cohen .P., T.( 1996). The AIDSs Knowledge Based Textbook, Second Edition, Little Brown.
8. 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.
9. 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.
10. 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.
11. Nissapatorn. V, Lee. C, Abdullah. 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.
12. 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..
13. 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.
14. Federle, M., P, (1988) A Radiologist Looks at Aids: Imaging Evaluation Based on Symptom Complexes.Radiology, 166:553-562.
15. 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.
16. 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.
17. of Central Nervous System Infections. Seminar in Roentgenology, VolXXXIV, No 2 (April): 123-143.
18. 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.
19. 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.
20. .
(c) mkareem 32

33. References
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. 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 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 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. AJNR Am J Neuroradiol, 18:1581-
1585.
25. Gifford, A., L., Frederick, M., Hecht,(2001). Evaluating HIV-infected Patients With Headache: Who Needs Computed Tomography?. Headache, 41:441-448.
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.
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. AJNR Am J Neuroradiol 16:1319-1327.
28. Thwaites. G.E., Hien. T. T. (2005). Tuberculous meningitis:many question, too few answers. Lancet Neuro. 4:160-70.
29. Engin.G., Acunas. B., Acunas. B., Tunaci. M. (2000). Imaging of Extrapulmonary Tuberculosis. Radiographics. 20:471-488.
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. Radiographics;20:449-470.
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. Radiology.143:703-707.
33. Popovich. M. J., Arthur.R.H., Helmer. E. (1989). CT of Intracranial Cryptococcosis. AJR; 154 (March):603-606.
34. Harrison. T. S (2000). Cryptococcus neoformans 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 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.
37. Wong.J., Quint.d. J.(1999). Imaging
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34. (c) mkareem 34

35. Pathogenesis in the brain
 Indeed, postmortem neuro-pathological series reveal that CNS abnormalities
occur in up to 90% of patient with advanced AIDS (Connor et al, 2006).
 Brain parenchyma  CSF (and reverse)  Infection of stromal cells,
macrophages, endothelial cell and choroids plexus . ependymal &
subependymal cells
 Damage to the nervous system via 3 ways:
 i. Direct infection/ killing or alteration of cellular
metabolic function (cytopathic effects). The retention of viral genome in
neural cells in a persistent latent form  cell dysfunction.
 ii. cytotoxic action of HIV-specific products or aberrantly secreted cellular
products
 In addition, autoimmune mechanisms and such factors as virus strain may
also play a role in nervous system dysfunction.
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36. Clinical Variables
:
 A • Sex – male or female
 B. Age – age recorded to the nearest year
 C. Neurological signs and symptoms -
 Signs - GCS, fever, neck stiffness and neurological findings.
 Symptoms:-hemiplFocal:egia, hemiparesis, slurred speech, CN palsy
 ii). Nonfocal symptoms-headache, seizure, abnormal behaviour,
altered sensorium
 D • CD4 count – A/C to 1993 revised CDC classification systems,
 Category 1 (early stage, CD4 ≥ 500cells/µl) ,
 category 2: (middle stage, CD4 200-499cells/ µl) and
 category 3 (late stage, CD4 <2000cells/µl).
 E • CT brain findings – edema, ring-lesion, nodular lesion,
 leptomeningeal enhancement, atrophy.
 F• Associated opportunistic or co-infection: Toxoplasma gondii, Cryptococcus
neoformans, CMV, Herpes virus, Hepatitis C and B viruses.
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37. Diagram of HIV & its protein
locations
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38.  HIV-1 Infection is associated with a
progressive loss of CD4+ T-cells
 STAGES OF HIV/AIDS CD4+ T CELL COUNT
Early < 500 x 10 000 000/l
Late < 200 x 10 000 000/l
Advanced < 50 x 10 000 000/l
 HIV plasma levels during all stages of infection range from
just 50 to 11 million virions per ml.
 The rate of loss of CD4+ T-cells is linked with an increase
in viral load.
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39. Methodology
Sample size calculation
Sample size was calculated using Power and Sample
software Where,
P0 = proportion of presence of neurological symptoms in
patient with positive scan = 0.373
p1 = proportion of absence of neurological symptoms in
patient with positive CT scan = 0.627
α = 0.05 , m=2 , = 80% = 0.8
Thus, sample size (n) = 45 power
To include twenty five percent (25%) drop-out:
Number of cases: 45 + 11 = 56
Total number of patients needed for the study is =
56.
Site: In Hospital Raja (c) mkareem
I Perempuan Zainab II 39