Rare disease

CASE REPORT

Is it toxoplasma encephalitis, HIV encephalopathy
or brain tuberculoma?
Amal Rashad Nimir,1 Emilia Osman,2 Ibrahim Abdel Aziz Ibrahim,3 Ahmed M Saliem4
1

Cyberjaya University College
of Medical Sciences,
Cyberjaya, Malaysia
2
Department of Parasitology,
UKM, Bangi, Selangor,
Malaysia
3
Department of Pharmacology
and Toxicology, Faculty of
Medicine, Makkah,
Saudi Arabia
4
Department of Anatomy,
Perdana University-Royal
College of Surgeons in Ireland,
Serdang, Selangor, Malaysia
Correspondence to
Dr Amal Rashad Nimir,
aralmadi@yahoo.com

SUMMARY
A 31-year-old Malaysian man was presented with an
episode of seizures by the roadside, after having been
recently diagnosed as HIV positive accompanied with
miliary tuberculosis. On physical examination, he was
oriented to person, but not to time or place. There was
no neck stiffness or papilloedema. The other systemic
examination was unremarkable. Chest examination
revealed crepitations at the upper zone of the right lung.
After diagnosis suspicion, the case was confirmed as
toxoplasma encephalitis by MRI and serological tests.
Patient was treated with trimethoprim/sulfamethoxazole
480–2400 mg/day with folinic acid supplement for
60 days. Two months later, a repeat brain MRI showed
resolution of the cerebral lesions.

BACKGROUND
Toxoplasmosis is an opportunistic infection caused
by Toxoplasma gondii, a ubiquitous obligate intracellular protozoan. T gondii causes encephalitis,
pneumonitis and disseminated infection in immunocompromised hosts, and leads to life-threatening
infections in some patients.1 Toxoplasmosis in those
patients is usually the result of reactivation of latent
infection rather than primary infection.2 3
Diagnosing cerebral toxoplasmosis in immunocompromised patients is often difficult because the
symptoms and signs are non-specific. Therefore, it is
important to take toxoplasmosis into account as one
of the differential diagnoses in febrile immunocompromised patients.

On physical examination, the patient is feverish
(temperature; 38.3°C), blood pressure is 110/60
and his heart rate is 110/min. The left cervical
lymph nodes are palpable and lung auscultation
revealed crepitation at the upper zone of the right
lung. There is no neck stiffness or papilloedema.
Other systemic examination is unremarkable.

INVESTIGATIONS
On admission, full blood count shows mild
anaemia (haemoglobin; 10.2 g/dl); white cell
count, 3000/ml; platelets, 181×103/ml and CD4
count of 36 cells/ml. The results for serum glucose,
electrolytes, urea, nitrogen and creatine are normal.
The results of cerebrospinal fluid (CSF) examination are as follows: opening pressure, 9.5 cm
H2O; lymphocytes, 5/mm3; protein, 153.7 mg/dl
and glucose, 79 mg/dl. Gram staining, acid-fast
staining and culture of the CSF did not reveal any
microorganisms. Chest x-ray shows features of
miliary TB with lobar consolidation and perihilar
infiltrate (figure 1). An MRI scan of the brain
revealed multiple, variable-sized ring-enhancing
lesions with surrounding oedema in the cerebral
hemispheres and brain stem (figure 2). The features
are suggestive of multiple brain abscesses. The
patient was treated empirically with intravenous
ceftrioxone, gentamycin and metronidazole.
Intravenous dexamethasone was also given to
reduce cerebral oedema. After 4 days, the patient
underwent another bout of seizures which lasted
for a minute it was relieved upon receiving a 10 mg

CASE PRESENTATION

To cite: Nimir AR,
Osman E, Ibrahim IAA, et al.
BMJ Case Rep Published
online: [ please include Day
Month Year] doi:10.1136/
bcr-2013-008803

A 31-year-old Malaysian man was picked up by the
ambulance crew from a roadside. According to eyewitnesses, the patient stopped by a shop and suddenly fell unconscious, and had generalised jerky
movements which lasted about 2 min. When the
ambulance arrived, the patient was alert, but still
drowsy. He was admitted to the Accident and
Emergency Department, Universiti Kebangsaan
Malaysia Medical Centre.
The patient is an intravenous drug abuser. He was
accidently diagnosed to be HIV positive 1 month
earlier in Hospital Kuala Lumpur. At that time, he
was admitted to the hospital due to prolonged fever
and productive cough. Acid-fast staining of the
sputum smear was positive for Mycobacterium
tuberculosis. He is currently on antituberculosis
(TB) treatment (Isoniazid 250 mg/day, Rifampicin
450 mg/day, Pyrazinamide 125 mg/day, Ethambutol
100 mg/day and Pyridoxine 10 mg/day).

Nimir AR, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-008803

Figure 1
pattern.

Chest x-ray revealed tuberculosis of miliary

1

Rare disease

Figure 2 MRI scans of the brain show multiple variable-sized
ring-enhancing lesions with oedema (A, B) suggest focal haemorrhage.

intravenous injection of diazepam. An infectious diseases physician was consulted, and he suggested serological study for toxoplasma antibodies. ELISA test shows positive antitoxoplasma
IgG with a titre exceeding 300 IU/ml.

TREATMENT
The
patient
received
trimethoprim/sulfamethoxazole
480–2400 mg/day with folinic acid supplement for 2 months.
Another MRI scan of the brain performed after treatment was
completed, which showed improvement of the multifocal granulomatous lesions, with decreased size and number of enhancing
lesions and a reduction in the amount of surrounding oedema
compared with the previous scan result (figure 3).

OUTCOME AND FOLLOW-UP
Two months later, a repeat brain MRI showed resolution of the
cerebral lesions.

DISCUSSION
The incidence of toxoplasmosis in HIV patients in Malaysia is
relatively high4 as toxoplasmosis is quite prevalent in this
2

Figure 3 MRI scans of the brain show improvement of the brain after
treatment for 2 months.
country.5 The patient has a complicated medical history, with
the positive HIV status and TB infection. Many differential
diagnoses were expected and had to be narrowed down to the
most probable cause of his presentation. Most febrile conditions
are readily diagnosed on the basis of presenting symptoms and a
problem-focused physical examination. Occasionally, simple
testing such as a complete blood count or urine culture is
required to make a definitive diagnosis. The initial approach to
the patient presentation should include a comprehensive history,
physical examination and appropriate laboratory testing.
Diagnostic clues often are not readily apparent on physical
examination in some cases; repeated examination may be essential. Careful attention to the skin, mucous membranes and
lymphatic system, as well as abdominal palpation for masses or
organomegaly, is important. The physician’s choice of imaging
should be guided by findings from a thorough history and physical examination.6 A suspect of primary central nervous system
(CNS) lymphoma, progressive multifocal leukoencephalopathy,
HIV encephalopathy and cytomegalovirus encephalistis were all
in the list of probable causes in our patients.
The preliminary evaluation helps in the formulation of a differential diagnosis and guides further studies that are more
invasive or expensive. The decision to obtain further diagnostic
Nimir AR, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-008803

Rare disease
studies should be based on abnormalities found in the initial
laboratory work-up and not represent a haphazard use of costly
or invasive modalities.
In this patient, brain MRI with contrast showed mass effect
and ring enhancement. Mass effect is characterised by the presence of swelling, oedema and mass effect on the surrounding
structures, whereas enhancement usually signifies the presence
of inflammation. Toxoplasma encephalitis, primary CNS lymphoma and tuberculoma are the leading diagnosis in developing
countries.7
In CNS lymphoma, MRI of the brain usually reveals multiple
nodular masses with no central liquefaction or differential signal
intensity. Although such lesions are usually associated with
mild-to-moderate perilesional oedema, it demonstrates a characteristic depression along the outer margins, which is consistent
with the ‘notch sign’.8 Toxoplasmosis typically occurs as a brain
lesion most commonly in AIDS, whereas malignant lymphoma
commonly manifests as a brain neoplastic lesion. However, it is
difficult to distinguish between the two, based on the brain
image results alone.9 Diagnosis confirmation by early biopsy is
recommended, yet in our case biopsy was considered to be a
final option, reserved until other suspected causes are excluded.
Definitive diagnosis of tuberculous meningitis (TBM) depends
upon the detection of the tubercle bacilli in the CSF. Every
patient with TBM should preferably be evaluated by imaging
with contrast enhanced CT either before or within the first 48 h
of treatment. TBM would have been a rare outcome in this
case, since it is usually more common in younger population.10
TBM is characterised by diffuse brain oedema and demyelination, which are usually extensive,11 unlike the findings of the
patient’s brain MRI. Microscopically, TBM is characterised by
microvascular necrosis with perivascular macrophage reaction
and demyelination along with focal glial nodules in the white
matter and occasional haemorrhagic lesions. Impaired consciousness, seizures, disseminated intravascular coagulation, and
signs and symptoms of meningitis with or without spinal fluid
changes characterise this syndrome.
Diagnosis of toxoplasmosis following HIV seroconversion is
often difficult because symptoms and signs are usually nonspecific. High fever is often the earliest sign; therefore, in a
febrile HIV patient with neurological signs, prompt diagnostic
workup is important. In this case, confirmation was obtained by
the high titre IgG antitoxoplasma antibodies. Timely initiation
of prophylaxis for opportunistic infections and their prompt
recognition and treatment are the only economically viable
options in Malaysia and other developing countries.7 The serological and immunological studies and the required imaging

(radiograph of the chest, ultrasonography and CT scan) if indicated can be performed in 1 day or after one outpatient visit.
A cost-effective individualised approach is essential to the evaluation of these patients, and without a thoughtful and focused
investigation, inappropriate tests might be performed.

Learning points
A high suspicion is important to diagnose cerebral
toxoplasmosis when an HIV patient presents with fever and
neurological signs, consequently toxoplasmosis should be
treated accordingly as symptoms quickly seize after appropriate
therapy was initiated.

Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

REFERENCES
1

2
3

4
5
6

7

8
9

10

11

Mele A, Paterson PJ, Prentice HG, et al. Toxoplasmosis in bone marrow
transplantation: a report of two cases and systematic review of the literature. Bone
Marrow Transplant 2002;29:691–8.
Kotton CN. Zoonoses in solid-organ and hematopoietic stem cell transplant
recipients. Clin Infect Dis 2007;44:857–66.
Edvinsson B, Lundquist J, Ljungman P, et al. A prospective study of diagnosis of
Toxoplasma gondii infection after bone marrow transplantation. APMIS
2008;116:345–51.
Nissapatorn V, Lee CKC, Khairul AA. Seroprevalence of toxoplasmosis among AIDS
patients in Hospital Kuala Lumpur. Singapore J Med 2003;4:194–6.
Veeranoot N. Toxoplasmosis: a silent threat in Southeast Asia. Res J Parasitol
2007;2:1–12.
Kupferwasser LI, Darius H, Muller AM, et al. Diagnosis of culture-negative
endocarditis: the role of the Duke criteria and the impact of transesophageal
echocardiography. Am Heart J 2001;142:146–52.
Adurthi S, Mahadevan A, Bantwal R, et al. Utility of molecular and serodiagnostic
tools in cerebral toxoplasmosis with and without tuberculous meningitis in AIDS
patients: a study from South India. Ann Indian Acad Neurol 2010;13:263–70.
Arora A, Kapoor A, Sharma A. Correspondence Re: MRI findings of primary CNS
lymphoma in 26 immunocompetent patients. Korean J Radiol 2010;11:702–3.
Utsuki S, Oka H, Abe K, et al. Primary central nervous system lymphoma in
acquired immune deficiency syndrome mimicking toxoplasmosis. Brain Tumor Pathol
2011;28:83–7.
Shin DW, Cha DY, Hua QJ, et al. Seroprevalence of Toxoplasma gondii infection and
characteristics of sero-positive patients in general hospitals in Daejeon, Korea.
Korean J Parasitol 2009;47:125–30.
Dastur DK. The pathology and pathogenesis of tuberculous encephalopathy and
radiculomyelopathy: a comparison with allergic encephalomyelitis. Childs Nerv Syst
1986;2:139.

Copyright 2013 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit
http://group.bmj.com/group/rights-licensing/permissions.
BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission.
Become a Fellow of BMJ Case Reports today and you can:
▸ Submit as many cases as you like
▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles
▸ Access all the published articles
▸ Re-use any of the published material for personal use and teaching without further permission
For information on Institutional Fellowships contact consortiasales@bmjgroup.com
Visit casereports.bmj.com for more articles like this and to become a Fellow

Nimir AR, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-008803

3