kuliah

1. Dr . PUJI PINTA O. SINURAT, SpS
Departemen Neurologi FK USU/
RSUP Haji Adam Malik
2016

2. Spektrum NeuroAIDS
• Primary complication
• (non-opportunistic disease)
– HIV-Dementia
– HIV-Sensory neuropathy
• Secondary complication
(opportunistic disease)
– Cerebral Toxoplasmosis
– TB Meningitis / tuberculoma
– Cryptococcal meningitis
– Other opportunistic diseases....

3. HIV Neuropathogenesis
 Chronic CNS infection begins during
primary systemic infection and
continues in nearly all untreated
seropositive individuals
 progress to HIV-1 encephalitis (HIVE)
 manifests as a clinical syndrome of
cognitive, motor, and behavioral
dysfunction known as the HIV-dementia

4. Blood BBB CNS
Infections
Neuronal
damage
Cognitive
Motor weakness
Encephalopathy
Blood
Brain parechyma Scarano et al Nature Vol 5 Jan 2005
HIV Entry into CNS

5. Komplikasi neurologi HIV
 Brain Predominantly nonfocal
AIDS dementia complex
Acute HIV-related encephalitis
Cytomegalovirus encephalitis
Varicella-zoster virus encephalitis
Herpes simplex virus encephalitis
Metabolic encephalopathies

6.  Brain Predominantly focal
Cerebral toxoplasmosis
Primary CNS lymphoma
Progressive multifocal leukoencephalopathy
Cryptococcoma
Brain abcess / tuberculoma
Neurosyphilis (meningovascular)
Vascular disorders

7.  Spinal cord
Vacuolar myelopathy
Herpes simplex or zoster myelitis
 Meninges
Aseptic meningitis (HIV)
Cryptococcal meningitis
Tuberculous meningitis
Syphilitic meningitis
Metastatic lymphomatous meningitis

8.  Peripheral nerve and root
Cytomegalovirus lumbar polyradiculopathy
 Virus or immune-related
acute and chronic inflammatory HIV polyneuritis
mononeuritis multiplex
sensorimotor demyelinating polyneuropathy
distal painful sensory polyneuritis
 Muscle
polymyositis and other myopathies

9. Perjalanan penyakit infeksi HIV
 Infeksi virus (2-3 minggu)  sindroma
retro-viral akut (2-3 minggu)  gejala
menghilang + serokonversi  infeksi kronis
HIV asimptomatik (rata2 8 thn)  infeksi
HIV / AIDS simptomatik (rata2 1,3 thn) 
kematian.
 Window period  masa dimana
pemeriksaan test serologis utk antibodi HIV
masih negatif, tapi virus sdh ada dlm darah
(sudah mampu menularkan kpd orang lain)

10. HIV dementia (AIDS Dementia
Complex)
 This progressive dementia occurs in AIDS,
owing to a direct primary HIV infection of
neurons or an indirect neurotoxicity induced
by presence of the virus in the brain
 Pathology: the virus may be transported into
the brain by infected peripheral monocytes
(Trojan horse theory).

11. Manifestasi klinis demensia HIV:
Cognititive disorders
Gangguan kognitif, kesulitan konsentrasi,
forgetfullness, cognitive slowing. Kadang2
agitasi, mania.
Pd std awal sulit membedakan dgn keluhan
psikiatri.
Motor abnormalities: ataksia, hiperrefleks.
Babinski refleks srg muncul.
Pada std lanjut : paraparese dgn inkontinansia
urin et alvii
Behavioural dysfunction : Apathy, altered
personality, disorientasi.
Std akhir Mutism

12. APNAC STUDY
Neurologic disorders are prevalent in HIV-positive outpatients
in the Asia-Pacific region
Neurology Vol 71(1), 1 July 2008, pp 50-56
Beijing Hongkong Bangkok KLumpur Jakarta
Neurocognitive
impairment
2/49
(4%)
14/61
(23%)
13/73
(18%)
2/39
(5%)
7/61
(11%)
Neuropathy 13/50
(30%)
9/62
(14%)
20/68
(30%)
8/40
(20%)
10/60
(17%)
Wright EJ, Brew B, Imran D, Kamarulzaman A, McArthur J
The Asia Pacific NeuroAIDS Consortium ( APNAC )

13. Anti Retroviral
 ARV reduce the opportunistic infection
 ARV can arrest HIV-dementia and
reverse its neurological disability.(Price J Infect
Dis. 2008 May 15 )
 Neurologist should have a competency
in prescribing ARV

14. Anti Retroviral Treatment
 HAART (highly active antiretroviral treatment )
 Combination of three ARV
 ARV indication
 AIDS defining illness
 CD4 < 350 cell/uL
 Viral load > 50.000 copy/ml
 When to start ? (first : treat opportunistic
infection, than start ARV)

15. Lamivudine
Zidovudine
Stavudine
Nevirapine Efavirenz
First Line ARV
(HAART : 3 drugs combination)
HAART : highly active antiretroviral therapy

16. ARV Lini Satu

17. First Line ARV (1)
Stavudine 2 X 1 . Neuropati, pankreatitis, atrofi otot
Lamivudin 2 X1
Efavirens 600 1 X 1, vivid dream, ngantuk, imbalance,
wanita hamil

18. First Line ARV (2)
Stavudine sda
Lamivudin sda
Nevirapin 1 X 1 2 minggu pertama, selanjutnya 2 X 1
Alergi, fungsi hati

19. First Line ARV (3)
Duviral : 2 X 1 (Zidovudin dan lamivudin)
Anemia, sakit kepala
Nevirapin sda

20. First Line ARV (4)

21. Second line ARV

22. ARV brain penetration
 Low
○ Tenofovir
○ Didanosine
○ Ritonavir
 Medium
○ Stavudine
○ Lamivudine
○ Efavirenz
○ Emtricitabine
 High
○ Zidovudine
○ Nevirapine

23. Initiation of ARV
Therapy
 Indication
 AIDS defining illness
 CD4 < 350 cell/uL
 Viral load > 50.000 copy/ml
 Patients preparation before starting ARV
 Longlive treatment
 Rule-out and treat opportunistic infection first
 ARV adverse effect
○ Side effect

24. Focal Brain Lesion (FBL)
Lesi fokal otak pd imaging ?
Efek desak ruang ?
HIV positif
Simptom intrakranial
YA
tidak

25. CEREBRAL TOXOPLASMOSIS
 Reactivation of latent infection
 Toxo seroprevalence 12-46%
 IgG indicates past infection (FN <3-6%)
 CD4 > 200 virtually excludes Toxo
 Over 80% have CD4 < 100
 Typically multiple ring enhancing lesions on CT/MRI
 27-43% have single lesions
 Up to 10% may have diffuse encephalitis without any
visible focal lesions

26. The course of HIV/AIDS
Notes:

28. MRI
CT Scan
Atrofi Meningeal
enhancement
hidrosefalus SOL
Evaluasi LCS Shunt
(kalau perlu)
Positif Negatif
Terapi sesuai
etiologi
Observasi
Lesi massa(-) Lesi massa (+)
Skema 2
Keluhan intrakranial
Skema-1. Algoritme Penatalaksanaan Keluhan Intraserebral bagi Penderita HIV-AIDS
normal

29. Terapi toksoplasmosis
Seumur hidup
Terapi sesuai
etiologi
Dekompresi dan
biopsi terbuka
Lesi massa intrakranial
Alert-lethargic
stabil
Steroid ? Stupor-koma
Perburukan cepat, massa besar
Dengan resiko herniasi
Lesi multipel Lesi tunggal
Serologi
toksoplasma
NegatifPositif
Obat antitoksoplasmosis
Perbaikan
Ya Tidak Biopsi stereotaktik
Ancaman herniasi
Skema-2. Algoritme Penatalaksanaan Lesi massa Intrakranial pada penderita HIV-AIDS

30. Toxoplasmosis – Clinical
Features
 Usually subacute over weeks
 Headache 50%
 Fever 45%
 Behaviour changes 40%
 Confusion 15-52%
 Focal signs
 Seizures 24-29%

31. TREATMENT
 Acute treatment : 3-6 weeks.
 Induction : pyrimethamine 200 mg
 First line :
○ Pyrimethamin 75-100 mg/day + sulfadiazine
+ folinic acid or
○ Pyrimethamin + clindamycin + folinic acid.
 Second line :
○ Azithromycin, clarithromycin, or atovaquone
can substitute for sulfadiazine.
 Glucocorticoid  life threatening condition.

32. TREATMENT
 Maintenance :
 Until the immune system has sufficiently
reconstituted.
 Pyrimethamine and sulfadiazine or
 Pyrimethamine and clindamycin.
 Stop :
 Asymptomatik.
 CD4+ > 200/cmm until 6 months.

33. CT - Multiple ring enhancing lesions
 Toxo more likely
 Tuberculomas still
possible

34. Differential Diagnosis
Toxoplasmosis P CNS L
Location Basal ganglia.
Gray-white junction
Periventricular
Number of lesion Multiple Solitary>multiple
Enhancement pattern Ring Heterogeneous or
homogeneous.
Edema Moderate to marked Variable
T2-weighted image
(lesion relative to
white matter)
Hyperintense Isointense to
hyperintense.
Diffusion-weighted
image
Usually hypointense Often hyperintense
(positive)

35. Differential Diagnosis
Toxoplasmosis P CNS L
MR perfusion Decreased Increased
MR spectroscopy Markedly elevated
lactate.
Markedly elevated
choline
SPECT thallium
(lesion relative to
white matter)
“Cold”-no thallium
uptake
“Hot”-increased
thallium uptake.
Other Toxoplasma IgG Ab
(+) (90% of patients)
EBV DNA amplified
by PCR in CSF
(most patients)

36. Cytomegalovirus infections
 Central or peripheral nervous system
 In adults occur in immunocompromised individual
 Etiology: CMV (DNA Virus) of the herpetic group
 Clinical features:
-Encephalitis  complication of organ
transplantation and AIDS. CD 4 < 50 cell/ mm3
- Symptoms enceph: headache, fever and
seizure
 Treatment: antiviral agent (ganciclovir or
foscarnet)