ANGGRAENI PARWATI

09-036
Kepaniteraan Ilmu Neurologi
Periode 15 Desember 2014 24 Januari 2015

 Toxoplasma gondii is known as one of the most common infectious

protozoan parasites that has a worldwide distribution.
Toxoplasma infection is largely asymptomatic, but in those individuals
who are immune-compromised with AIDS, malignant patients under
chemotherapy or organ transplant recipients can become disseminated
and cause severe toxoplasmosis and/or encephalitis .
T. gondii may serve as one factor that can enhance the immunodeficiency
found after HIV-1 infections.

Toxoplasmosis is generally a late complication of HIV infection and

usually occurs in patients with CD4 + T-cell counts below 200/l.

In adults, most T.gondii infections are subclinical, but severe infections

can occur in patients who are immunocompromised (A.I.D.S,
Malignancy).
AIDS associated toxoplasma encephalitis results from reactivation of
chronic latent infection in more than 95% of patients.
In patients with AIDS seropositive for T.gondii, the risk for cerebral
toxoplasmosis approaches 30%.
Toxoplasmosis is the most common cause of focal brain lesions in
patients with AIDS and frequently localizes to the basal ganglia, although
other sites in the brain and spinal cord may be affected, multiple foci are
seen more often.

Pathogenesis
In patients with AIDS, tissue cysts rupture and the released bradyzoites
may multiply locally and spread to other organs.

The pathology of Toxoplasma infection is due to the invasion process

initiating the lytic cycle that consequently leads to cell and tissue
destruction.
In the host cell cytoplasm, T. gondii induces the formation of a
parasitophorous vacuole that contains secretions of both parasite and
host proteins that normally promote phagosome maturation, , and
thereby prevent lysosome fusion (Dubey et al, 1998; Carruthers, 2002).
T. gondii excretory/secretory antigens (ESAs) represent the majority of
the circulating antigens in host sera of patients with acute toxoplasmosis
(Pereira-Chioccola et al, 2009).
ESAs include the tachyzoite, sporozoite and encysted bradyzoite stages
(Tilley et al, 1997).

Pathogenesis
Anti-ESA antibodies develop in high titers when circulating blood
tachyzoites are present in AIDS-associated CT patients (Meira et al,
2008).
Toxoplasma infection results in pathological changes such as
inflammation and is usually followed by necrosis.
Among patients with AIDS, CT is a multifocal process that occurs
spontaneously.

The use of the highly sensitive technique of magnetic resonance imaging

(MRI) reveals that >80% of patients will have multiple lesions (Ciricillo &
Rosenblum, 1990).
The spontaneous and simultaneous development of multifocal brain
lesions strongly indicates that although CT arises because of reactivation
of a latent infection, the multiple areas of the brain that are involved are
likely a result of the hematogenous spread of the parasite, and
involvement of the brain is due to the particular proclivity of T. gondii for
causing disease in the CNS (Luft & Remington, 1992).

Pathogenesis
An US study demonstrated a significant association between CD4 counts
of 200-499 cells/mm3 and Toxoplasma-seropositivity in patients (Falusi et
al, 2002).
The authors were unable to provide an explanation for this association
except that patients with low CD4 counts were more likely to be foreign
born.
Primary chemoprophylaxis or antiretroviral drugs including HAART (if
available) should be instituted to these patients after clinical evaluation.

Clinical implication
Congenital toxoplasmosis

The level of anti-Toxoplasma (IgG) antibodies does not appear to be affected by

antiretroviral drugs or therapeutic regimes/prophylaxis used to treat toxoplasmosis
in these patients (Machala et al, 2009)
In recent years, an HIV-infected pregnant woman with CT who was at risk for
transmitting HIV (low CD4 and high viral load) and Toxoplasma infections to her
fetus; she responded well to anti-Toxoplasma therapy and HAART (Nogueira et al,
2002).
In this case, the combined Toxoplasma therapy (pyrimethamine and sulfadiazine)
and HAART were benefitial not only to the mother but also prevented transmission
to the fetus.

Cerebral toxoplasmosis

The risk of developing CT among seropositive patients with AIDS was 27 times that
of seronegative ones (Oksenhendler et al, 1994).
AIDS patients who are Toxoplasma seropositive, have CD4 count of <100
cells/cumm, and failure to receive prophylaxis are among the identified risk of
developing CT (Luft and Remington, 1992; Nascimento et al, 2001; Nissapatorn et
al, 2004)

Clinical implication
Cerebral toxoplasmosis

The clinical presentations of CT depend on the number of lesions and location.

Headache, hemiparesis and seizure (Nissapatorn et al, 2004; Vidal et al, 2005a) are
among the most common neurological presentations found in CT patients. Other
clinical manifestations include disarthria, movement disorders, memory and
cognitive impairments and neuropsychiatric abnormalities.

It is very rare for patients with CT to present as a neuropsychiatric illness with an

acute psychosis followed by a rapid mental and somatic decline, however one case
has been reported in a patient with AIDS (Ilniczky et al, 2006).

In hyperkinetic movements, holmes (also known as rubral or midbrain tremor)

tremor is the earliest reported symptom of CT and might present with other focal
neurological signs that indicates a midbrain localization (Koppel & Daws, 1980).

Clinical implication
Cerebral toxoplasmosis

The appearance of hemichoreahemiballism is considered as a pathognomonic of CT

and is most commonly associated with a subthalamic abscess (Navia et al, 1986;
Maggi et al, 1996). The presence of hemichoreahemiballism in CT patients is low
(7.4% of cases) compared to the pathological studies which show 50% of
Toxoplasma abscesses occur in the basal ganglia (Navia et al, 1986; Maggi et al,
1996).

Generalized chorea may occur as a result of bilateral abscesses of toxoplasmosis

(Gallo et al, 1996).

Myoclonus, is generalized and elicited by sudden auditory stimuli that resembles a

startled response, has also been described in AIDS-associated CT patients (Maher et
al, 1997).

A case of focal dystonia of the left arm and hand has been reported in an AIDS
patient due to the right lenticular nucleus and thalamic abscesses of toxoplasmosis
(Tolge & Factor, 1991).

Clinical implication
Extracerebral toxoplasmosis

Occular toxoplasmosis is the most common form of ECT associated with CT, being
detected in 50% of ECT in AIDS patients and has the best prognosis (Rabaud et al,
1994; Zajdenweber et al, 2005).

Neuropathology of toxoplasmosis
Multifocal necrotizing encephalitis is the predominant neuropathological
finding of CT in AIDS patients.

Localization of multiple with ring enhancing lesions on neuroimaging in

basal ganglia, frontoparietal cortex and thalamus suggests
haematogenous spread.
Three morphological patterns of brain lesions based on the stage of
infection and degree of tissue reaction (Shankar et al, 2005):

Acute stage : appearance of a necrotizing abscess or encephalitis seen as poorly

circumscribed necrotic foci with variable degrees of haemorrhage, perifocal edema,
acute and chronic inflammation, macrophage infiltration, with numerous T. gondii
tachyzoites and encysted bradyzoites along the periphery. Also common are
vascular thrombosis/fibrinoid necrosis of vessel walls, with polymorph infiltration,
hypertrophy and the presence of tachyzoites in the hypertrophie arterial wall.

Neuropathology of toxoplasmosis
Three morphological patterns of brain lesions based on the stage of
infection and degree of tissue reaction (Shankar et al, 2005):

Chronic lesion : organized abscesses are found in CT cases treated for 2 weeks and
seen as well circumscribed foci of central necrosis with a rim of congestion. In
contrast to the acute phase, the central foci of an acellular necrosis is surrounded by
a granulomatous reaction, with macrophages containing tightly packed lipid and
haemosiderin, prominent hypertrophic occlusive arteritis with dense lymphocytic
cuffing, and only a few organisms.

Patients treated for 1 month show chronic abscesses in CT appear as small cystic
cavities or linear orange-yellow scars and macrophages containing lipid and
haemosiderin surrounded by a dense gliotic reaction. Calcification of vessels occurs
and organisms are rarely found. In addition, a CAT scan can present as a diffuse,
non-necrotizing, rapidly progressive encephalitis.

The histological appearance seen as nodules of micrioglial cells with

encysted bradyzoites and dispersed tachyzoites within the nodules.

Choosing between Toxo TB Bacterial

Absces
Empiric Anti Toxoplasmic
No history of toxo prophylaxis

Empiric Anti TB drug

CD4 > 200

Thorax photo : Miliar TB

Empiric Antibiotic for Bacterial Brain Absces

Neuroimaging study : compatible with bacterial brain absces

Empiric anti Toxoplasmic Treatment

Trimethoprim/sulfamethoxazole (Co-trimoxazole, 5/25
mg/kg PO or intravenous (IV) every 12 h for 4-6 weeks)
(Canessa et al, 1992).
Clindamycin and pyrimethamine or sulfadiazine (Katlama et
al, 1996a; Tsai et al, 2002),
Clarithromycin and pyrimethamine (Fernandez-Martin et al,
1991),
Clindamycin and 5- Fluoro-uracil (Dhiver et al, 1993),
Azithromycin and pyrimethamine (Saba et al,
1993;Jacobson et al, 2001),

Clindamycin and fansidar (Nissapatorn et al, 2004),

Sulfadoxine and pyrimethamine (Amogne et al, 2006), and
Atovaquone (Torres et al, 1997).

Empiric anti Toxoplasmic Treatment

Pyrimethamine and sulfadoxine twice a week appears to give

promising results for prevention of CT.

A current guideline recommends the use of a daily dose of a doublestrength tablet of co-trimoxazole in Toxoplasma-seropositive
patients who have a CD4 cell count below 100 cells/cumm (CDC,
2009).

Secondary prophylaxis for CT patients;

the combination of pyrimethamine (25-50 mg/day) plus sulfadiazine (500 mg

every 6 h) plus eucovorin (10-20 mg/day), thrice weekly (Podzamczer et

al, 1995) or the same doses of sulfadiazine twice a day (Jordan et al,
2004) is an alternative option among non-compliance patients.
The recommendation is for pyrimethamine plus clindamycin (600 mg
clinidamycin every 8 h) for patients who are intolerant to sulfa drugs
(CDC, 2009).
Co-trimoxazole (960 mg twice daily) is another potential drug used in
secondary prophylaxis for patients with CT (Duval et al, 2004). This
agent (2.5/12.5 mg/kg PO every 12 h)

Empiric anti Toxoplasmic Treatment

2004

Pyrimethamine-sulfadoxine bid po
Drug allergy 34.2 %

Clindamycin 600 mg qd po
2005 - present
Pyrimethamine 200 mg load 75 mg/d
Clindamycin 600 mg qd po

Department of Neurology RSCM Hospital Indonesia University

Highly active anti-retroviral therapy

(HAART)
HAART should be started at least 2 weeks after an anti-Toxoplasma
regimen was initiated in these patients (Manzardo et al, 2005; PereiraChioccola et al, 2009).
In HIV-infected patients receiving HAART, primary prophylaxis for CT can
be safely discontinued in patients whose CD4 cell counts increase to >200
cells/mm3 (CDC, 2009).
Secondary prophylaxis can be safely discontinued in CT patients receiving
HAART with CD4 cell count of > 200 cells/cumm after 6 months (PereiraChioccola et al, 2009). This same prophylaxis should be reintroduced in
patients with CD4 cell count of < 200 cells/cumm (CDC, 2009).
While, primary and secondary prophylaxis against CT can also be safely
discontinued after the CD4 cell count has increased to 200 cells/cumm for
more than 3 months in HIV-infected patients receiving HAART (Miro et al,
2006).

IDENTITAS
Nama

: Tn. AO

Usia

: 22 tahun

Alamat

: OKSOP

Suku

: Ngalum

Tanggal masuk RS : 09 Desember 2014

Anamnesis
Keluhan utama : Sakit kepala sejak 1 tahun lalu.
Riwayat penyakit sekarang:
Pasien datang dengan keluhan sakit kepala sejak 1 tahun yang lalu
dan dirasakan semakin memberat setiap harinya. Sakit kepala yang pasien
rasakan seperti ditusuk-tusuk. Pasien tidak bisa beraktivitas karena sakit
kepala tersebut. Selain itu, pasien juga mual (+) serta muntah (+) apabila
pasien batuk dan bangun dari tidur. Apabila kepala ditegakkan, sakit kepala
terasa semakin hebat. Demam (-), batuk sesekali, BAB dan BAK tidak ada
keluhan. Mata kanan pasien sudah tidak dapat melihat dan mata kiri pasien
pandangannya kabur sejak 5 bulan yang lalu.

Riwayat penyakit dahulu:

Hipertensi (-), diabetes mellitus (-)

PEMERIKSAAN FISIK
Kesadaran

: Composmentis

GCS

: E4V5M6

Nadi

: 124 x/menit

Tekanan Darah

: 120/70 mmHg

Suhu

: 39,1 C

Respirasi

: 24 x/menit

Umur Klinis

: 30 an

Bentuk Badan

: Atletikus

Gizi

: Cukup

Kulit

: Coklat tua

Kuku

: Sianosis (-)

Turgor

: Cukup

Kel. Getah Bening

: Tidak teraba membesar

Pembuluh Darah
A. Carotis

:
: Palpasi kanan dan kiri : Teraba kuat, cukup
angkat, reguler
: Bising (-)

Auskultasi

PEMERIKSAAN REGIONAL

Kepala
: Normocephali
Kalvarium : Tidak ada kelainan
Mata
: Konjungtiva tidak pucat,
Sklera tidak ikterik
Hidung
: Bentuk biasa, lapang, sekret -/Mulut
: Tidak ada kelainan
Telinga
: Bentuk biasa, serumen -/Leher
: Tidak ada kelainan

PEMERIKSAAN REGIONAL

Toraks : Normochest
Jantung :

Inspeksi :iktus kordis tidak terlihat

Palpasi :Iktus kordis tidak teraba
Perkusi :Batas kanan jantung ICS V linea parasternal
dextra, Batas kiri jantung ICS V linea midklavikularis
sinistra
Auskultasi :BJ I dan II normal, murmur -, gallop -

PEMERIKSAAN REGIONAL

Paru-paru

Inspeksi
Palpasi
Perkusi
Auskultasi

:pergerakan dinding dada simetris

:vocal fremitus simetris
:sonor simetris kanan kiri
:BND vesikuler, Wheezing -/-, Rhonki -/-

Abdomen

Inspeksi
Auskultasi
Palpasi
Auskultasi

:perut tampak datar

:BU (+) 3 x/menit
:supel, NT (-)
:timpani, tidak ada nyeri ketok

Hepar
Lien
Vesika Urinaria
Extremitas
Sendi
Gerakan Leher
Gerakan Tubuh
Nyeri Ketok
Nyeri Sumbu

: Tidak teraba membesar

: Tidak teraba membesar
: Bulging -, nyeri tekan : Simetris, Akral hangat, Oedem (-)
: Tidak ada kelainan
: Tidak ada keterbatasan Range of
Movement
: Tidak ada keterbatasan Range of
Movement
::-

PEMERIKSAAN NEUROLOGIS
Rangsang Meningeal

Kaku kuduk

:-

Brudzinski I

:-

Brudzinski II

: -/-

Kerniq

: -/-

Laseque

: >70/ >70

Saraf Kranial
N.I (Olfaktorius)
Kanan

Kiri

Cavum nasi

lapang

lapang

Test Penghidu

normosmia

normosmia

Visus kasar

1/6

Lihat warna

Baik

Baik

Lapangan pandang

Baik

Baik

N. II (Optikus)

Funduskopi

Tidak dilakukan

N. III, IV, VI
(Okolomotorius, Trochlearis,
Abdusen)
Sikap bola mata
Ptosis
Strabismus
Eksoftalmus
Endoftalmus
Diplopia
Deviasi Konjugee
Pergerakan Bola mata
Lateral kanan
Lateral Kiri
Atas
Bawah
Berputar

: simetris
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: Baik
: Baik
: Baik
: Baik
: Baik

Pupil:
Bentuk
: Bulat
Isokor
: 3mm/3mm,
Tepi rata, ditengah.
Reflek cahaya:
Langsung
:+/+
Tidak langsung
:+/+
Reflek akomodasi
:+/+

N. V (Trigeminus)
Motorik
- Membuka Mulut
- Gerakan Rahang
- Menggigit

: Baik
: Baik
: Baik

Sensorik
- Rasa Nyeri
- Rasa Raba
- Rasa Suhu

: Baik
Baik
: Baik
Baik
:
tidak dilakukan

Refleks:
Reflek Kornea
Reflek Masseter

:
:

+
+

+
+

N.VII (Fasialis)
Sikap wajah (saat istirahat) : Simetris
Mimik

: Biasa

Angkat Alis

: Simetris, kanan = kiri

Kerut Dahi

: Simetris, kanan = kiri

Lagoftalmus

: Tidak ada

Kembung Pipi

: Simetris, kanan = kiri

Menyeringai

: Sulcus nasolabialis kanan tampak

mendatar

Fenomena Chovstek

:-

N.VIII (Vestibulocochlearis)
Vestibularis
Nistagmus
Vertigo

:: tidak ada

Kokhlearis
Suara bisik
Gesekan jari
Tes Rinne
Tes Weber
Tes Schwabach

: kanan = kiri
: kanan = kiri
: +/+
: Tidak ada lateralisasi
: Sama dengan pemeriksa

N. IX, X (Glosofaringeus, Vagus)

Arkus Faring
Palatum Mole
Disfoni
Rinolali
Disfagi
Batuk
Menelan
Mengejan
Refleks Faring
Refleks Okulokardiak
Refleks Sinus Karotikus

: simetris, uvula ditengah

: intak, simetris
: Tidak ada
: Tidak ada
: Tidak ada
: Tidak ada
: Baik
: Baik
: Baik
: Positif
: Positif

N.XI (Asesorius)
Menoleh (kanan,kiri,bawah) : Baik
Angkat Bahu

: Baik

N.XII (Hipoglosus)
Sikap lidah dalam mulut

: simetris

Julur lidah

: simetris

Gerakan lidah

: baik

Tremor

: tidak ada

Fasikulasi

: tidak ada

Tenaga otot lidah

: Berkurang

MOTORIK
Kekuatan motorik:
5555
5555
Tonus Otot:
Lengan
Fleksor
Ekstensor

5555
5555

kanan
: Normotonus
: Normotonus

kiri
Normotonus
Normotonus

: Normotonus
: Normotonus

Normotonus
Normotonus

Tungkai
Fleksor
Ekstensor

Trofi Otot
Lengan :
Tungkai :

Eutrofi
Eutrofi

Eutrofi
Eutrofi

Gerakan Spontan Abnormal

Kejang
Tetani
Tremor
Khorea
Atetosis
Balismus
Diskinesia
Mioklonik

: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada
: tidak ada

Koordinasi
Statis

Duduk

: baik.

Berdiri

: tidak dilakukan

Tes Romberg

: tidak dilakukan

Telunjuk Hidung

: baik

Jari-jari

: baik

Tumit lutut

: baik

Dinamis

REFLEKS
Refleks Tendo
Biseps
Triseps
Knee Pes Reflex
Achilles Pes Reflex

Refleks Abnormal
: ++ / ++
: ++ / ++
: ++ / ++
: ++ / ++

Refleks Kulit
Telapak kaki
Kulit perut
Kremaster
Anus Interna
Anus Externa

: ++ / ++
: ++ / ++
: tidak dilakukan
: tidak dilakukan
: tidak dilakukan

Babinski
Chaddock
Oppenheim
Gordon
Schaeffer
Mendel Bechterew
Hoffman Trommer
Klonus lutut
Klonus Kaki

: -/: -/: -/: -/: -/: -/: -/: -/: -/-

Sensibilitas
Eksteroseptif
- Rasa raba

: kanan = kiri

- Rasa nyeri

: kanan = kiri

- Rasa suhu

: tidak dilakukan

Propioseptif
- Rasa sikap

: baik, kanan = kiri

- Rasa getar

: tidak dilakukan

Vegetatif
Miksi

: Baik

Defekasi

: Baik

Salivasi

: tidak ada

Sekresi keringat

: umum

Fungsi Seks

:-

Fungsi Luhur
Memori

: baik

Bahasa

: baik

Afek dan emosi

: irritable

Kognitif

: baik

Tanda Regresi
Refleks menghisap

:-

Refleks menggigit

:-

Refleks memegang

:-

Snout Reflex

:-

Pemeriksaan
Laboratorium (9 Desember 2014)

Masa pembekuan
menit

: 3.3

APTT

: 29.5

SGOT

: 23

PT

: 10.9

SGPT

: 43

IMR

: 1.0

Ureum

: 36

Creatinin

: 1.1

Fibrinogen

: 152 (L)

Asam urat

: 4.6

D-dimer

Na

: 145

: 3.3 (L)

Ca

: 8.9

HBsAg

: non reaktif

Anti HCV

: non reaktif

Anti HIV (ELISA)

: 0.10 (non-reaktif)

Protein total

: 5.9 (L)

Albumin

: 2.6 (L)

Globulin

: 9 10

: 350

Pemeriksaan
Urin & parasitologi (10 Desember 2014)

Berat jenis

1.015

Leukosit

0/LBP

Warna

kuning

Eritrosit

0/LBP

Kejernihan

jernih

Epitel

0/LBP

Esterase leukosit -

Silinder

0/LBP

Nitrir

Bakteri

0/LBP

Darah

pH

6.0

Protein

Glukosa

Bilirubin

Urobilinogen

0.2

Keton

Pemeriksaan

9 Des 2014

13 Des 2014

14 Des 2014

16 Des 2014

LED

33 (H)

15 (H)

10

26

Hb

12.4 (L)

10.8 (L)

10.5 (L)

10

Leukosit

6.9

3.4 (L)

2.8 (L)

2.4

Eritrosit

5.15

4.56

4.44 (L)

4.23

Basofil

30

Eosinofil

0 (L)

Neutrofil
batang

0 (L)

0 (L)

0 (L)

Neutrofil
segmen

84 (H)

82 (H)

81 (H)

Limfosit

3 (L)

6 (L)

8 (L)

Monosit

13 (H)

9 (H)

9 (H)

81

Trombosit

128000 (L)

78 (L)

73 (L)

MCV

73 (L)

72 (L)

70 (L)

MCH

24.1 (L)

23.7 (L)

23.6 (L)

MCHC

32.8

33.1

33.7

Pemeriksaan
15 Des 2014
Protein total

: 5.5 (L)

Kultur darah

:-

Albumin

: 2.5 (L)

Kultur urin

:-

globulin`

: 3.0

Pemeriksaan
9 Desember 2014

11 Desember 2014

CT brain

CT angiografi cerebral

CVD infark luas di

temporoparietooccipital sinistra

Tidak tampak nyata stenosis, aneurisma

maupun malformasi vaskular pada CTA
ini.

Ro. Thorax
TB paru dupleks kemungkinan komponen
bronchopneumoni sinisra

CT scan
Gambaran CVD infark di lobus
temporoparietooksipitalis sinistra

Pemeriksaan
15 Desember 2014

11 Desember 2014

CT brain + kontras

CT angiografi cerebral

Gambaran abses multipel di temporal dan

parietooccipital sinistra

Gambaran CVD infark di lobus

temporoparietooksipitalis sinistra

USG abdomen
Splenomegali, nefrolithiasis multipel
kanan, susp.cystitis

PEMERIKSAAN
Hematologi

Kesan subtipe limfosit

CD4

CD4 Absolute

70 (L)

CD4%

23 (L)

CD8

CD8 Absolute

89 (L)

CD8%

29

Rasio CD4:CD8

0.78

Linfosit T helper rendah dan T

supressor rendah dengan rasio CD4CD8 normal

Choosing between Toxo TB Bacterial

Absces
Empiric Anti Toxoplasmic
No history of toxo prophylaxis
Empiric Anti TB drug
CD4 > 200
Thorax photo : Miliar TB

Empiric Antibiotic for Bacterial Brain Absces

Neuroimaging study : compatible with bacterial brain absces

Diagnosis
Diagnosis kllinik

Cephalgia

Penurunan visus

Diagnosis topis

Temporal sinistra

Parieto-occipital sinistra

Diagnosis etiologik

Infeksi dd/ Toxoplasma gondii

Mycobacterium tuberculosis

Diagnosis patologi anatomi

Sel mikroglia dengan bradiziot encysted dan tachyzoite yang berada di dalam nodul

Pengobatan