2. Chief complaint
• 34 year old male known C13 claims
compliance to medication presented to ER
with c/c/o One episode of fits this morning
3. HPI
• One of his family member witnesses the
episode and stated it as “ Jerky movements of
all four limbs and patient was confused for
one hour after the episode . Denies any
sphincter incontinence”.
• Patient was also complaining of diffuse
headache.
• Denies any neck stiffness/ vomitings.
4. Past medical history
• Diagnosed with C13 5 years ago
• From a different parish hospital.
• Patient is on ZIDOLAM-N ,BACTRIM
DS,Vitamin B pills.
• AH: No known drug allergies
• SH: Not a smoker .but a social drinker.
5. Examination
• Patient is in nil CPD
• M/M: Pink, moist, anicteric, acyanotic,afebrile.
• Neuro: Drowsy ,arousable
alert,orient*3
Pupils- NSRL . CN II-XII - Intact
Power 5/5 in all extremities
Plantars- flexor
Cerebellar – Normal exam
7. Provisional diagnosis
• Patient was admitted to hospital with
following provisional diagnosis in view of his
C13 status
• GTCS for evaluation
Toxoplasmosis
Cns lymphoma
12. Management
• Patient was treated for 2 weeks as inpatient
and advised to do repeat CT scan to see the
lesions
• Due to financial constraints we were not able
to repeat the study.
• Eventually patient was discharged on oral
medication for 4 weeks
13. Follow up
• Patient was advised to come for ward review
in 4 weeks
• Patient was never compliant to his medication
as an out patient and admitted twice in next 6
months with recurrent seizure episode.
• No repeat CT scan was done all the while.
14. Challenges in management
• Few medications were available that too for
limited time periods
• Not able to trace his CD 4 count through out
the clinical encounter as patient is from
different parish region
• Failed in counseling the patient regarding
adherence to medication
16. Toxoplasma
• The word Toxoplasma originated from the Greek word toxon,
which meant "bow." This became the basis for the Latin word
toxicum, which meant "poison." The original Greek meaning is
the one used for the word Toxoplasma, meaning "bow shaped
organism.
• The word gondii is the name of a North African desert rodent
which is related to the organism that T. gondii was originally
found in.
17. Toxoplasmosis
• Toxoplasmosis is the leading cause of focal central
nervous system (CNS) disease in AIDS.
• CNS toxoplasmosis in HIV-infected patients is usually
a complication of the late phase of the disease.
• Typically, lesions are found in the brain and their
effects dominate the clinical presentation.
18. Toxoplasmosis
• Rarely, intraspinal lesions need to be considered
in the differential diagnosis of myelopathy.
• The decision to treat a patient for CNS
toxoplasmosis is usually empiric. Primary therapy
is followed by long-term suppressive therapy,
which is continued until antiretroviral therapy can
raise CD4+ counts above 200 cells/µL.
21. • The only known definitive hosts for Toxoplasma gondii are members
of family Felidae (domestic cats and their relatives).
• Unsporulated oocysts are shed in the cat’s feces . Although oocysts
are usually only shed for 1-2 weeks, large numbers may be shed.
Oocysts take 1-5 days to sporulate in the environment and become
infective. Intermediate hosts in nature (including birds and rodents)
become infected after ingesting soil, water or plant material
contaminated with oocysts .
• Oocysts transform into tachyzoites shortly after ingestion. These
tachyzoites localize in neural and muscle tissue and develop into
tissue cyst bradyzoites .
• Cats become infected after consuming intermediate hosts
harboring tissue cysts . Cats may also become infected directly by
ingestion of sporulated oocysts. Animals bred for human
consumption and wild game may also become infected with tissue
cysts after ingestion of sporulated oocysts in the environment .
22. Humans can become infected by any of several routes:
• Eating undercooked meat of animals harboring tissue cysts .
• Consuming food or water contaminated with cat feces or by
contaminated environmental samples (such as fecal-contaminated
soil or changing the litter box of a pet cat) .
• Blood transfusion or organ transplantation .
• Transplacentally from mother to fetus .
• In the human host, the parasites form tissue cysts, most commonly
in skeletal muscle, myocardium, brain, and eyes; these cysts may
remain throughout the life of the host. Diagnosis is usually achieved
by serology, although tissue cysts may be observed in stained
biopsy specimens .
• Diagnosis of congenital infections can be achieved by detecting T.
gondii DNA in amniotic fluid using molecular methods such as PCR .
23. Pathophysiology
• CNS toxoplasmosis results from infection by the
intracellular parasite Toxoplasma gondii.
• It is almost always due to reactivation of old CNS lesions or
to hematogenous spread of a previously acquired infection.
• Occasionally, it results from primary infection.
• CNS disease occurs during advanced HIV infection when
CD4+ counts are less than 200 cells/µL. The greatest risk is
in patients with CD4+ counts below 50 cells/µL.
24. Epidemiology
• Clinical CNS toxoplasmosis occurs in 3-15% of patients with
AIDS in the United States. Some clinically silent lesions
come to diagnosis only at autopsy. Clinical CNS
toxoplasmosis occurs in as many as 50-75% of patients in
some European countries and in Africa.
• In 5% of patients, CNS toxoplasmosis is the presenting
opportunistic infection of AIDS. The incidence rate has
decreased due to the use of highly active antiretroviral
therapy (HAART) and prophylaxis against Pneumocystis
jiroveci infections with trimethoprim-sulfamethoxazole,
which is also effective against toxoplasmosis.
25. Clinical Presentation
• CNS toxoplasmosis begins with constitutional
symptoms and headache. Later, confusion and
drowsiness, seizures, focal weakness, and language
disturbance develop. Without treatment, patients
progress to coma in days to weeks.
• On physical examination, personality and mental status
changes may be observed. Seizures, hemiparesis,
hemianopia, aphasia, ataxia, and cranial nerve palsies
may be evident. Occasionally, symptoms and signs of a
radiculomyelopathy predominate.
26. Differential Diagnosis
• CNS Lymphoma in HIV
• Mycobacterial infection (eg, tuberculous abscess,
tuberculoma)
• Fungal infection (eg, cryptococcosis, candidiasis)
• Chagas disease
• Bacterial abscess (eg, Nocardia)
• Neurosyphilis
• Cardioembolic Stroke
• Cytomegalovirus Encephalitis in HIV
• Progressive Polyradiculopathy in HIV
• Vacuolar Myelopathy in HIV
• Progressive Multifocal Leukoencephalopathy
27. Serologic studies
• Serologic studies in patients with CNS toxoplasmosis may
demonstrate rising titers of anti-toxoplasma
immunoglobulin G (IgG) antibodies. An immunoglobulin M
(IgM) antibody response is seen in cases of newly acquired
toxoplasmosis or Toxoplasma encephalitis.
• However, anti-Toxoplasmagondii IgG detection may be
unreliable in immunodeficient individuals who fail to
produce significant titers of specific antibodies. In one
study, 16% of patients with a clinical diagnosis and 22% of
patients with a histologic diagnosis of toxoplasmosis had
undetectable anti-T gondii IgG levels. Causes of false-
negative results also include recent infection and
insensitive assays
28. Definitive diagnosis
• Definitive diagnosis of CNS toxoplasmosis requires the following[1] :
• Compatible clinical findings
• Identification of one or more mass lesions by CT, MRI, or other
radiographic testing
• Detection of T gondii in a clinical sample
• Detection of T gondii DNA on polymerase chain reaction (PCR)
testing of cerebrospinal fluid (CSF) samples may facilitate the
diagnosis and follow-up of toxoplasmosis in patients with AIDS.[2] In
a study using the B1 gene, rapid PCR showed a sensitivity of 83.3%
and specificity of 95.7%.[3]
• CSF findings may also include elevated protein and variable glucose
and WBC counts. The presence of Epstein-Barr virus DNA in the CSF
favors the diagnosis of lymphoma.
• Lumbar puncture may be contraindicated because of increased
intracranial pressure, however. For many clinicians, therefore, CNS
toxoplasmosis is an empiric diagnosis that relies on clinical and
radiographic improvement in response to specific anti-T gondii
therapy. In patients who fail to respond to specific therapy, brain
biopsy can be used to secure a clinical sample for testing.[1
29. Imaging
• A brain CT scan or MRI with and without contrast is
indicated for all patients presenting with altered
mental status, headaches, seizures, or focal neurologic
signs. MRI clearly is the superior technique but is not
available universally.
• Single or multiple hypodense or hypointense lesions in
white matter and basal ganglia with mass effects may
be observed on CT or MRI scans. Lesions may enhance
in a homogeneous or ring pattern with contrast (see
the images below). Imaging studies may be normal in
diffuse toxoplasmosis.
30. T1-weighted axial brain magnetic resonance image at
the level of the basal ganglia in a 24-year-old man with
human immunodeficiency virus infection. The image
shows hypointense lesions in the region of the thalami
(arrows) caused by toxoplasmosis
31. T1-weighted axial brain magnetic resonance image at the
level of the upper lateral ventricles in a 24-year-old man
with human immunodeficiency virus infection (same
patient as in the previous image). The image shows a
hypointense mass compressing the right lateral ventricle
(arrow)
32. Transaxial contrast-enhanced computed tomography scan in a 24-year-
old man with human immunodeficiency virus infection and central
nervous system toxoplasmosis (same patient as in the previous 2
images). This image was obtained after the patient received 20 days of
treatment, with resultant clinical improvement, and shows a low-
attenuating mass with minor peripheral ring enhancement. Note the
reduction in the mass effect.
34. Imaging
• Single lesions favor the diagnosis of
lymphoma over that of toxoplasmosis.
However, while multiple lesions are more
common than single lesions in toxoplasmosis,
in one study 27% of patients had a single
lesion on CT scan. In the same study, 14% had
a single lesion on MRI. MRI is more sensitive
than CT scan in detecting multiple lesions.
35. Imaging
• If the initial imaging study is normal or shows atrophy
or focal signal abnormalities (but no mass lesion),
diagnostic consideration should be given to
meningitides, AIDS dementia complex, or progressive
multifocal leukoencephalopathy.
• If imaging shows one or more focal mass lesions with
impending herniation, an open biopsy with
decompression is indicated. Treatment for lymphoma,
toxoplasmosis, or other opportunistic infections and
neoplasms is initiated, depending on biopsy results.
36. Scintigraphy
• Where available, thallium-201 single-photon
emission computed tomography (201 TI SPECT) or 18-
fluorodeoxyglucose positron emission tomography
(18FDG-PET) may be useful in distinguishing between
lymphoma and toxoplasmosis. Lymphoma shows an
increased uptake as compared with toxoplasmosis.
These tests have high specificity but low sensitivity.
37. Brain Biopsy
Indications for brain biopsy include either of
the following:
• Single mass lesion and negative serologic
results
• No response to 14 days of empiric therapy
• Diagnostic yield of stereotactic biopsies
increases with the number of specimens
obtained.
41. Treatment
• Primary therapy is given for 6 weeks, followed by
long-term suppressive therapy at reduced doses,
with the duration determined by response to highly
active antiretroviral therapy (HAART). The long-term
suppressive therapy can be discontinued in patients
with persistent elevation of CD4+ counts greater than
200 cells/µL and resolution of lesions on MRI.
42. Prevention
• To prevent primary toxoplasmosis, patients should
avoid eating undercooked meat and should wash their
hands carefully after contact with soil or cats. Patients
who are seropositive for Toxoplasma should be started
on prophylaxis against CNS toxoplasmosis if their CD4+
count drops below 100 cells/μL.[1]
• The preferred prophylactic regimen is one double-
strength tablet of trimethoprim-sulfamethoxazole
(TMP-SMZ) daily, which also provides prophylaxis
against Pneumocystis jiroveci pneumonia (PCP).[1]