HEADACHES AND CONFUSION
A 28-year-old black South African theatre nurse in London is admitted to the emergency department complaining of headaches and confusion. Her headaches have developed over the past 3 weeks and have become progressively more severe. The headaches are now persistent and diffuse. Her friend who accompanies her says that she has lost 10 kg in weight over 6 months and has recently become increasingly confused. Her speech is slurred.
While in the emergency department she has a generalized tonic–clonic convulsion.
She is thin and weighs 55 kg. Her temperature is 38.5°C. There is oral candidiasis. There is no lymphadenopathy. Examination of her cardiovascular, respiratory and gastrointestinal systems is normal. Neurological examination prior to her fit showed her to be disorientated in time, place and person. There were no focal neurological signs. Funduscopy
shows bilateral papilloedema
• What is the cause for this woman’s headaches, confusion and fits?
• What is the underlying diagnosis?
• How should this woman be further investigated and treated?
This woman has cerebral toxoplasmosis secondary to HIV infection. This condition is caused by the protozoan Toxoplasma gondii which primarily infects cats but can also be carried by any warm blooded animal. In the West, 30–80 per cent of adults have been infected by ingesting food or water contaminated by cat faeces, or by eating raw meat
from sheep or pigs which contain Toxoplasma cysts. After ingestion by humans the organism divides rapidly within macrophages and spreads to muscles and brain. The immune system rapidly controls the infection, and the cysts remain dormant. The primary infection is generally asymptomatic, but can cause an acute mononucleosis-type illness with
generalized lympadenopathy and rash. It may leave scars in the choroid and retina and small inflammatory lesions in the brain. If the host then becomes immunocompromised the organism starts proliferating causing toxoplasmosis. This is an AIDS-defining illness, but is relatively rare in solid organ transplant recipients. Cerebral toxoplasmosis usually
presents with a subacute illness comprising fever, headache, confusion, fits, cognitive disturbance, focal neurological signs including hemiparesis, ataxia, cranial nerve lesions, visual field defects and sensory loss. Movement disorders are common due to involvement of the basal ganglia. CT or magnetic resonance imaging (MRI) will usually show multiple
bilateral ring-enhancing lesions predominantly located near the grey–white matter junction, basal ganglia, brainstem and cerebellum. The clinical and radiological differential diagnoses include lymphoma, tuberculosis and secondary tumours. Anti-toxoplasma antibody titres should be measured, but are not always positive.
The other clues in this case to the diagnosis of HIV infection include the patient’s country of origin, the weight loss and oral candidiasis. The headaches and papilloedema are caused by raised intracranial pressure from the multiple space-occupying lesions. The hyponatraemia is due to the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) consequent to the raised intracranial pressure.
This woman should be started on anticonvulsants to prevent further seizures. Treatment is started with high-dose sulfadiazine and pyrimethamine together with folinic acid to prevent myelosuppression. There should be a rapid clinical and radiological improvement. In cases that have not responded within 3 weeks, a biopsy of one of the lesions should be
considered. Cerebral toxoplamosis is uniformally fatal if untreated, and even after treatment neurological sequelae are common.
The patient should be counselled about HIV infection and consented for an HIV test. Her HIV viral load and CD4 count should be measured, and antiretroviral drugs started. She should be advised to contact her previous sexual partners so that they can be tested and started on antiretroviral therapy. She should also tell her occupational health department
so that the appropriate advice can be taken about contacting, testing and reassuring patients. The risk of HIV transmission from a healthcare worker to a patient is very small.
• Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with AIDS.
• Patients can present with headache, confusion, fits and focal neurological deficits.
• The clinical and radiological response to treatment is usually rapid.