Headache in an HIV positive patient: diagnostic challenges and approach to treatment 

Case presentation

A 31-year-old man with known HIV presented with a 1-month history of global, constant headache. He reported a single episode of collapse with transient loss of consciousness that prompted presentation to the emergency department (ED). Past medical history included HIV with poor adherence to antiretroviral therapy (ARV) – latest blood CD4 count 140 cells/μL (range 500–1500 cells/μL), plasma HIV load 200 copies/mL. He reported no history of previous opportunistic infections. He was allergic to penicillin and took mirtazapine for depression. Originally from the Democratic Republic of Congo, he had not left the UK for the previous 10 years. There was no history of recreational drug use. Systems review was unremarkable.

On examination, the patient was alert and his Glasgow Coma Scale was 15/15. Observations were within normal parameters and he was afebrile. On examination he had mild pain on neck flexion but no true neck stiffness. There was no rash, photophobia or other abnormal findings. Peripheral nervous system and cranial nerve examinations were normal.

Initial blood tests are summarised in Table 1. Imaging comprised a chest radiograph and cranial computerised tomography (CT), which were both reported as normal. A lumbar puncture was performed, revealing a lymphocytic pleocytosis and an elevated opening pressure of 25 cm of water. Cerebrospinal fluid (CSF) samples were sent for microbiology (including rapid mycobacterial and fungal tests) and virology (Table 2).

Differential diagnosis

The differential diagnosis of prolonged headache in an HIV positive patient from a tropical region is broad; with a mild lymphocytic pleocytosis in the CSF, this includes tuberculosis (TB), viral meningoencephalitis, Listeria and cryptococcal meningitis. Space occupying lesions are another cause of headache in HIV. In developed countries, the most common causes are toxoplasmosis and primary CNS lymphoma.¹ Infections, such as tuberculomas and aspergillomas, can also present as space-occupying lesions. In patients from developing countries, neurocystericosis should be considered in the differential. Other causes of a persistent headache range from imported infections like malaria, drug-induced headache, and, considering that HIV can be associated with a pro-coagulant state,² venous sinus thrombosis.

Initial management

In a severely immunocompromised patient presenting with persistent, prolonged headache with a lymphocytic CSF, empirical treatment for likely infectious causes was commenced pending further results. Intravenous aciclovir and high-dose co-trimoxazole to cover Listeria were started in the ED (amoxicillin is first line for suspected Listeria meningitis, with co-trimoxazole used if, as here, there is a clear penicillin allergy). Given the sub-acute onset and history of emigration from a TB-endemic area, it was felt that empiric treatment for tuberculous meningitis using standard quadruple therapy was also indicated.

After 48 hours, the full results of the CSF sample were available (Table 2). CSF culture was negative, as was extended viral polymerase chain reaction (PCR); aciclovir and co-trimoxazole were therefore stopped. Mycobacterial smear and TB PCR were negative, but as these tests are relatively insensitive in the context of TB meningitis (sensitivities reported as 45–80%³), TB treatment was continued pending further imaging and results.

On the third day, MRI of the brain was performed to identify possible meningeal or parenchymal pathology. This demonstrated normal brain parenchyma and meninges. However, an increased superior sagittal sinus diameter, suspicious of a venous sinus thrombosis (Fig 1), was identified. A magnetic resonance venogram confirmed this diagnosis (Fig 2⇓).

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Fig 1.

Magnetic resonance image (MRI) of brain. A – axial T2w MRI at time of diagnosis demonstrates ‘round’ appearance of superior sagittal sinus (arrow), suggestive of distal occulusion by thrombus. B – this appearance has resolved on follow-up MRI after successful treatment with anticoagulation, with return to the normal ‘triangular’ shape.

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Fig 2.

Magnetic resonance venogram. A – nearly complete occlusion of the distal segment of the superior sagittal sinus with thrombus at time of diagnosis. B – following anticoagulation therapy, there is reconstitution of flow within the sinus.

Case progression

Based on current Royal College of Physicians’ guidelines,⁴ anticoagulation therapy was started. The guidelines suggest warfarin; although in a patient with known variable adherence, decisions on anticoagulation must reflect their wishes and the need to optimise concordance. With previous poor attendance, at follow up, warfarin – with the requirement for regular monitoring – would be a high-risk strategy without proper safeguards in place. Although low molecular weight heparin injections would have alleviated the need for monitoring and could be administered in the community by a district nurse to ensure treatment was received, the patient declined long-term injections. A novel anticoagulant with oral administration and no need for regular monitoring would have been a simple solution but the potential interaction with ARVs precluded this.

Following discussion with the patient, inpatient warfarin loading, with the need for regular INR (International Normalised Ratio) monitoring clearly explained, was identified as a possible solution. The patient left hospital when the INR reached a therapeutic level. With text and telephone reminders, the patient attended for all scheduled appointments and completed the 6-month treatment course.

Key learning points

• The differential diagnosis of headache in HIV is broad. Infective and non-infective causes should be considered, with previous residence, travel history and degree of immunosuppression taken into account.

• Where there is suspicion of intracranial infection, antimicrobial therapy should be promptly commenced with cover for viral, mycobacterial and fungal organisms as appropriate.

• HIV is a risk factor for thrombosis. In an HIV positive patient with long-standing headache, venous sinus thrombosis should be included in the differential. An MRI brain can offer a diagnostic clue.

• Current guidelines for the treatment of venous sinus thrombosis suggest anticoagulation with warfarin. Risks and benefits should be discussed with the patient and strategies to facilitate compliance put in place.

Conflicts of interests

The authors have no conflicts of interest to declare.