Abstract:
Cerebral toxoplasmosis can affect a patient who is immunocompromised
with chronic liver disease. Liver cirrhotic patients with central
nervous system (CNS) infection could easily be misdiagnosed for hepatic
encephalopathy. A case of cerebral toxoplasmosis in an HIV-seronegative
patient with liver cirrhosis in a low-resource setting is reported.
Although the cerebral toxoplasmosis improved with medical treatment, the
patient died from progressive hepatic failure. Despite the usually poor
prognosis, early diagnosis and prompt treatment of CNS infection
complicating immunosuppression would prevent early death.
Keywords : Liver, cirrhosis, brain, toxoplasmosis, sepsis,
encephalopathy
Key Clinical message
Liver cirrhotic patients with central nervous system (CNS) infection
could easily be misdiagnosed for hepatic encephalopathy. A clinical
suspicion of a cranial infection would necessitate a brain CT or an MRI
to exclude the presence of CNS lesions.
INTRODUCTION
CNS infection often develops as an opportunistic infection in patients
with impaired host defence mechanisms due to malignancy, diabetes
mellitus, alcoholism, liver cirrhosis and, the prognosis is usually
poor1, 2. It develops either by spread from a
contiguous focus or by haematogenous spread from a distant focus, such
as intra-abdominal infection, endocarditis, urinary tract infection, or
pulmonary infection. It is rare and life-threatening in decompensated
liver cirrhosis. Liver cirrhosis is an immune-compromised state because
of reticuloendothelial dysfunction and porto-systemic
shunting3. Bacterial infections in cirrhosis are
common, particularly in decompensated patients and account for
significant mortality 4, 5. A case of a cerebral
parasitic toxoplasmosis in an HIV-seronegative patient with liver
cirrhosis is reported.
CASE HISTORY/ EXAMINATION
A 40-year-old African man was admitted as an emergency with a sudden
left arm and leg weakness. He had no history of hypertension, diabetes
mellitus, cardiovascular disease, atrial fibrillation or human
immunodeficiency virus (HIV) infection. He was single and a severe
alcohol consumer. On admission, he was conscious with a Glasgow Coma
Scale score of 15. His blood pressure was 120/80 mmHg, pulse rate
80/minute and regular, respiratory rate 20/min, and normal body
temperature, 37°C. The conjunctivae were pink and oral mucosa moist.
Chest and cardiovascular examinations were unremarkable. Abdominal
examination revealed dilated supraumbilical veins consistent withcaput medusa a sign of chronic liver disease and portal
hypertension. Apart from a nodular liver, there was no other stigmata of
chronic liver disease. He had a left hemiparesis, but there was no neck
stiffness nor flapping tremor indicating meningism or encephalopathy
respectively. The laboratory test results revealed anaemia (Haemoglobin
7.6 g/dl) , a normal white cell count (WBC 9.5 x
109/mm3, thrombocytopenia (119 x 109/ mm3), negative
HIV serology and malaria parasite, normal urea, creatinine, clotting
screen and serum albumin. Urinary urobilinogen, glucose, bilirubin and
ketone were negative. Liver function tests and a toxoplasma IgG serology
were not done due to financial constraints. Abdominal ultrasound showed
a nodular liver with irregular borders. A cerebral computed tomography
(CT) scan revealed multiple cerebral contrast ring-enhancing lesions
with massive perifocal oedema and mass effect with effacement of the
right frontal horn (figure 1).The findings were suggestive of cerebral
toxoplasmosis and CNS tuberculosis was a possible differential. The
patient was treated empirically for cerebral toxoplasmosis with a
combination of double strength pyrimethanine (dihydrofolate
reductase inhibitor ) and sulphadiazine (sulphonamide antibiotic )
(960mg) thrice daily for 6 weeks, vitamin B1, proton pump inhibitor
(omeprazole) and physiotherapy. There were both clinical (regaining of
motor strength in both left upper and lower limbs) and radiological (CT
scan) response (figure 2) after a week of treatment. The patient was
discharged a week later with continuation of medical treatment. He
returned after 12 months with decompensated liver disease and died from
hepatic encephalopathy a few months later.
DISCUSSION
The case demonstrated the presentation of cerebral toxoplasmosis in an
HIV-negative patient immunocompromised from probable alcoholic liver
cirrhosis. The presumptive diagnosis was made from the clinical
findings, ultrasound of the liver, and a brain CT scan. The neurological
symptoms were relieved following the empirical treatment of cerebral
toxoplasmosis. The patient, however, died of hepatic encephalopathy from
the progressive liver disease about a year later. Cirrhotic patients are
susceptible to several infectious diseases, such as septicaemia,
meningitis, pneumonia, urinary tract infection, and spontaneous
bacterial peritonitis (SBP) 5. Six (11%) of 53 cases
of brain abscess had liver cirrhosis, presenting with non-specific
symptoms and all died soon after 6] The high
mortality in cirrhotic patients is firstly due to the difficulty in
differentiating brain abscess from hepatic encephalopathy. Only 34% of
the patients have the complete triad of headache, fever, and focal
neurological deficits 1] In the advanced stage of
liver cirrhosis, hepatic encephalopathy is common and usually presents
with disorientation, confusion, drowsiness and coma. Furthermore,
cirrhotic patients can often have episodes of fever caused by
endotoxaemia or SBP. Neck stiffness occurs in only 8% of patients with
brain abscess and it is not always easy in clinical settings to detect
mild neurological findings in patients with impaired consciousness.
Secondly, bacteria infections worsen hepatic failure. The systemic
inflammatory response syndrome (SIRS) from increased endotoxins, bile
acids, nitric oxide, and cytokines such as tumour necrosis factor-
α and interleukin 6 , may occur resulting in sepsis, renal
failure, encephalopathy and death. It is important to start treatment as
quickly as possible to prevent SIRS as the cytokine cascade is usually
irreversible. Thirdly, most cirrhotic patients are not surgical
candidates because of their bleeding tendency and low hepatic reserve.
Only 33% of cirrhotic patients received surgical treatment, compared
with 66% of non-cirrhotic patients 1. Liver
dysfunction leads to several abnormalities of defence mechanisms because
of the depressed humoral and cell-mediated immunity. Bacterial
translocation from the intestine induces bacteraemia, and impaired
hepatic bacterial clearance results in failure to control bacteraemia3] Severe bacteraemia may cause infections of
several organs, but pathogenic bacteria may not be identified in 30% of
brain abscesses 1, 4. In the present case, the
causative pathogen was the parasite, Toxoplasma gondii. T.
gondii infection of humans occurs either congenitally or by ingestion
of foodstuffs contaminated by infected cat faeces or lamb or pork
contaminated with T. gondii cysts 7. Primary
infection in immune competent host is asymptomatic or may produce a mild
flu-like illness, malaise, headache, cervical lymphadenopathy. Infection
acquired during pregnancy may lead to serious fetal malformations8. After primary infection cysts are formed in the
tissue and remained inactive until reactivation. Cellular immunity
mediated by T cells, macrophages and cytokines plays a crucial role in
controlling the tissue cysts 9. The infection is
self-limiting in immunocompetent individuals because an efficient immune
control limits the dissemination of the rapidly multiplying tachyzoite
stage 7. However, the parasite still remains viable in
the tissue cysts. Chronically infected individuals who possess defects
in cell-mediated immunity as in chronic liver disease (CLD), HIV/AIDS
etc, are at risk for reactivation of the infection and its
dissemination, causing serious complications and death10- 12. T. gondii is the most frequent obligate
intracellular protozoan causing opportunistic infections in
immunocompromised patients mostly in the developing world10. An association between T. gondii infection
and chronic liver disease (CLD) has been observed. Co-infection in bothT. gondii / hepatitis B virus (HBV) and T. gondii /
hepatitis C virus (HCV) was 33.3% and 31.4% , respectively with a
highly significant association between T. gondii parasitaemia and
HCV viral load. There was also a significant increase of liver enzymes
in the serum of patients positive for T. gondii compared with
negative patients 11.Toxoplasma seropositivity was
higher in patients with Child-Pugh class C CLD than Child- Pugh class A
and, may signify disease evolution 12. Several studies
have reported the parasite found in 20%- 90% of patients with
cirrhosis through IgG and polymerase chain reactions PCR tests13. The three forms of cerebral toxoplasmosis are
focal toxoplasma meningoencephalitis, multifocal encephalitis and
diffuse toxoplasma meningoencephalitis. The common presentations include
decreased consciousness, headache, hemiparesis, cranial nerve palsy,
seizure, meningeal signs, dementia and psychosis 13,
14. Diagnosis is considered from clinical findings, CT scan, or
magnetic resonance imaging (MRI) of the brain with serological findings1.
CONCLUSIONS
Cerebral toxoplasmosis can affect an HIV-negative patient who is
immunocompromised with liver cirrhosis. Cirrhotic patients with CNS
infection could easily be misdiagnosed for hepatic encephalopathy. A
clinical suspicion of a cranial infection is important when encountering
cirrhotic patients with disturbance of consciousness and fever. Brain CT
or MRI must be considered to exclude the presence of CNS lesions. Early
treatment is important for this complication of immunosuppression which
has a poor prognosis.