HIV ENCHEPHALITIS

Dr . PUJI PINTA O. SINURAT, SpSDepartemen Neurologi FK USU/

RSUP Haji Adam Malik2016

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....

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

Blood BBB CNS Infections

Neuronal damage

CognitiveMotor weaknessEncephalopathy

Blood

Brain parechyma Scarano et al Nature Vol 5 Jan 2005

HIV Entry into CNS

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

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

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

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

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)

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).

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

APNAC STUDYNeurologic 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 JakartaNeurocognitive

impairment2/49(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 )

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

Anti Retroviral Treatment HAART (highly active antiretroviral treatment )

Combination of three ARV ARV indication

AIDS defining illnessCD4 < 350 cell/uLViral load > 50.000 copy/ml

When to start ? (first : treat opportunistic infection, than start ARV)

Lamivudine

Zidovudine Stavudine

Nevirapine Efavirenz

First Line ARV(HAART : 3 drugs combination)

HAART : highly active antiretroviral therapy

ARV Lini Satu

First Line ARV (1)

Stavudine 2 X 1 . Neuropati, pankreatitis, atrofi ototLamivudin 2 X1Efavirens 600 1 X 1, vivid dream, ngantuk, imbalance, wanita hamil

First Line ARV (2)

Stavudine sdaLamivudin sdaNevirapin 1 X 1 2 minggu pertama, selanjutnya 2 X 1Alergi, fungsi hati

First Line ARV (3)

Duviral : 2 X 1 (Zidovudin dan lamivudin)Anemia, sakit kepala Nevirapin sda

First Line ARV (4)

Second line ARV

ARV brain penetration Low

○ Tenofovir ○ Didanosine○ Ritonavir

Medium○ Stavudine○ Lamivudine○ Efavirenz○ Emtricitabine

High○ Zidovudine○ Nevirapine

Initiation of ARV Therapy Indication

AIDS defining illnessCD4 < 350 cell/uLViral load > 50.000 copy/ml

Patients preparation before starting ARVLonglive treatmentRule-out and treat opportunistic infection firstARV adverse effect

○ Side effect

Focal Brain Lesion (FBL)

Lesi fokal otak pd imaging ?

Efek desak ruang ?

HIV positif

Simptom intrakranial

YA

tidak

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

The course of HIV/AIDS

Notes:

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

Terapi toksoplasmosisSeumur hidup

Terapi sesuaietiologi

Dekompresi dan biopsi terbuka

Lesi massa intrakranial

Alert-lethargic stabil

Steroid ? Stupor-komaPerburukan cepat, massa

besarDengan 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

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

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.

TREATMENT Maintenance :

Until the immune system has sufficiently reconstituted.

Pyrimethamine and sulfadiazine orPyrimethamine and clindamycin.

Stop :Asymptomatik.CD4+ > 200/cmm until 6 months.

CT - Multiple ring enhancing lesions

Toxo more likely

Tuberculomas still possible

Differential DiagnosisToxoplasmosis 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)

Differential DiagnosisToxoplasmosis 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)

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)