Toxoplasma gondii is a common protozoan parasite that usually causes asymptomatic infection but can cause severe toxoplasmosis and encephalitis in immunocompromised individuals. Toxoplasmosis often occurs in AIDS patients with CD4+ T-cell counts below 200/μl and is the most common cause of brain lesions in AIDS patients, frequently affecting the basal ganglia. The pathology involves tissue cyst rupture, parasite multiplication and spread, leading to cell and tissue destruction. Diagnosis is based on clinical presentation, neuroimaging showing ring-enhancing lesions, and response to anti-toxoplasma treatment.
Toxoplasma gondii is a common protozoan parasite that usually causes asymptomatic infection but can cause severe toxoplasmosis and encephalitis in immunocompromised individuals. Toxoplasmosis often occurs in AIDS patients with CD4+ T-cell counts below 200/μl and is the most common cause of brain lesions in AIDS patients, frequently affecting the basal ganglia. The pathology involves tissue cyst rupture, parasite multiplication and spread, leading to cell and tissue destruction. Diagnosis is based on clinical presentation, neuroimaging showing ring-enhancing lesions, and response to anti-toxoplasma treatment.
Toxoplasma gondii is a common protozoan parasite that usually causes asymptomatic infection but can cause severe toxoplasmosis and encephalitis in immunocompromised individuals. Toxoplasmosis often occurs in AIDS patients with CD4+ T-cell counts below 200/μl and is the most common cause of brain lesions in AIDS patients, frequently affecting the basal ganglia. The pathology involves tissue cyst rupture, parasite multiplication and spread, leading to cell and tissue destruction. Diagnosis is based on clinical presentation, neuroimaging showing ring-enhancing lesions, and response to anti-toxoplasma treatment.
Toxoplasma gondii is a common protozoan parasite that usually causes asymptomatic infection but can cause severe toxoplasmosis and encephalitis in immunocompromised individuals. Toxoplasmosis often occurs in AIDS patients with CD4+ T-cell counts below 200/μl and is the most common cause of brain lesions in AIDS patients, frequently affecting the basal ganglia. The pathology involves tissue cyst rupture, parasite multiplication and spread, leading to cell and tissue destruction. Diagnosis is based on clinical presentation, neuroimaging showing ring-enhancing lesions, and response to anti-toxoplasma treatment.
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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 -
: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
