HIV Neurocomplications Flashcards
HIV: Neurocomplications - Focal Neurological Lesions
- Toxoplasmosis
- Primary CNS Lymphoma
- TB
Toxoplasmosis
Toxoplasmosis
- accounts for around 50% of cerebral lesions in patients with HIV
- constitutional symptoms, headache, confusion, drowsiness
- CT: usually single or multiple ring enhancing lesions, mass effect may be seen
- management: sulfadiazine and pyrimethamine
Primary CNS Lymphoma
Primary CNS lymphoma
- accounts for around 30% of cerebral lesions
- associated with the Epstein-Barr virus
- CT: single or multiple homogenous enhancing lesions
- treatment generally involves steroids (may significantly reduce tumour size), chemotherapy (e.g. methotrexate) + with or without whole brain irradiation. Surgical may be considered for lower grade tumours
Differentiating between toxoplasmosis and lymphoma
Differentiating between toxoplasmosis and lymphoma is a common clinical scenario in HIV patients. It is clearly important given the vastly different treatment strategies.
Toxoplasmosis:
- Multiple lesions
- Ring or nodular enhancement
- Thallium SPECT negative
Lymphoma:
- Single lesion
- Solid (homogenous) enhancement
- Thallium SPECT positive
Most effective method to help differentiate = THALLIUM SPECT
However, given the more limited availability of SPECT compared to CT, many patients are treated empirically on the basis of scoring systems e.g. there is a 90% likelihood of toxoplasmosis if all the following criteria are met:
- toxoplasmosis IgG in serum
- CD4 < 100 and not receiving prophylaxis for toxoplasmosis
- multiple ring enhancing lesions on CT or MRI
TB
Much less common than toxoplasmosis or primary CNS lymphoma
CT: single enhancing lesion
HIV Neurocomplications - Generalised Neurological Disease
- Encephalitis
- Cyptococcus
- Progressive multifocal leukoencephalopathy (PML)
- AIDS dementia complex
Encephalitis
- May be due to CMV or HIV itself
- HSV encephalitis but is relatively rare in the context of HIV
- CT: oedematous brain
Cryptococcus
- Most common fungal infection of CNS
headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit - CSF: high opening pressure, India ink test positive
- CT: meningeal enhancement, cerebral oedema
- Meningitis is typical presentation but may occasionally cause a space occupying lesion
Progressive Multifocal Leukoencephalopathy (PML)
- Widespread demyelination
- Due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
- Symptoms, subacute onset : behavioural changes, speech, motor, visual impairment
- CT: single or multiple lesions, no mass effect, don’t usually enhance. MRI is better - high-signal demyelinating white matter lesions are seen
AIDS Dementia Complex
- Caused by HIV virus itself
- Symptoms: behavioural changes, motor impairment
- CT: cortical and subcortical atrophy
Cryptococcal Meningitis - Example Question
A 30 year-old HIV positive South African woman presents to the emergency department with a 12 day history of fever and headache. On examination she is found to have a 6th nerve palsy, papilloedema and erythematous skin papules across her torso. She is not on any medication.
Investigations:
CD4 count 90 cells / mm³
CT head: Normal
What is the most appropriate immediate management?
Intravenous ceftriaxone Anti-retroviral therapy Rifampicin, isoniazid, pyrazinamide & ethambutol Intravenous albendazole & hydrocortisone > Intravenous amphotericin B & flucytosine
This is a classical presentation of cryptococcal meningitis - typically there is a sub-acute onset of symptoms and the disease is associated with raised intracranial pressure (leading to the papiloedema and the falsely localising 6th nerve palsy). This raised intracranial pressure (ICP) is thought to be caused by the yeast cells and fungal polysaccharides forming microscopic plugs and blocking CSF resorption in the subarachnoid villi. The best management would be intravenous anti-fungal agents, such as amphotericin B and flucytosine. Therapeutic lumber puncture is also advocated to reduce ICP. Anti-retroviral (ARV) therapy should not be started immediately, as there is a very high risk of the patient developing IRIS (immune reconstitution inflammatory syndrome). Instead, ARVs should be delayed for several weeks or months after initiating treatment.
HIV Neurocomplications - Difficult Diagnosis - Example Question:
A 36-year-old male from India presents with worsening headache and vomiting. He is known to have HIV but has been lost to follow up over the last 5 years. His CD4 count from his last appointment was 400.
On examination he has no localising signs however fundoscopy revealed papiloedema.
Investigations:
haemoglobin 115 g/L (115-165)
white cell count 9.4 × 109/L (4.0-11.0)
platelet count 220 × 109/L (150-400)
erythrocyte sedimentation rate 50 mm/1st h (<30)
serum urea 7.0 mmol/L (2.5-7.0)
serum creatinine 105 mol/L (60-110)
serum alanine aminotransferase 17 U/L (5-35)
serum aspartate aminotransferase 26 U/L (1-31)
Cryptococcal antigen test Negative
CD4 Count 65 cells/mm3
CT Head 5cm ring enhancing lesion in right temporal lesion with surrounding oedema
What is most appropriate management?
Amphotericin, Fluconazole and prednisolone Rifampicin, Isoniazid, Pyrazinamide, Ethambutol and prednisolone Trimethorpim-Sulphamethoxazole, Rifampicin, Isoniazid, Pyrazinamide, Ethambutol and prednisolone Start prednisolone but defer treatment until lumbar puncture performed > Pyrimethamine, Sulfadiazine, Rifampicin, Isoniazid, Pyrazinamide, Ethambutol, and Prednisolone
The question represents a real diagnostic conundrum. You should automatically think of compliance issues given that the patients has defaulted from treatment and is therefore unlikely to have been controlling his HIV. The CD4 count of 400 is therefore not going to be representative of his current immune system.
This leads us to the differential diagnosis of a intra-cerebral ring enhancing lesion in a severely immunocompromised host. This includes tuberculosis, lymphoma, toxoplasmosis and cryptococcus amongst others.
Amphotericin and fluconazole is used in the initial 2 week phase of treatment for cryptococcal meningitis. However we are told that the cryptococcal antigen test is negative. This test has a relatively high sensitivity and specificity is therefore reassuring.
We are also told that the patient has papilloedema and a 5cm lesion with oedema, as a result attempting a lumbar puncture at this early stage is fraught with risk. Although vital to diagnosis it would be prudent to reduce the intra-cerebral swelling first by which time the patient may have seriously deteriorated, therefore empirical treatment becomes a priority.
Diagnosis of CNS tuberculosis is notoriously difficult and without access to CSF it is likely that empirical treatment will be required in the interim. When CSF is available culture, staining and PCR can be used to help detect the organism. Toxoplasmosis is treated with pyrimethamine and sulfadiazine as a first line. Again, empirical treatment may be required before access to CSF is available. As a result the correct answer is treatment of TB and Toxoplasmosis with steroids to reduce oedema.
Primary CNS Lymphoma - Example Question
A 45-year-old man is reviewed in the HIV clinic. He was diagnosed with HIV 25 years ago and has enjoyed good health on highly active antiretroviral treatment until around 4 years ago when he had an episode of Pneumocystis jirovecii pneumonia.
Today he is somewhat confused. His partner reports that he has been complaining of headaches for several weeks and has also been uncharacteristically aggressive.
His latest CD4 count is 29 cells/µl. An MRI (T1 C+) is requested:
PASSMED SEE PRIMARY CNS LYMPHOMA
What is the most appropriate treatment?
Sulfadiazine + pyrimethamine Sulfadiazine + pyrimethamine + steroids > Steroids + methotrexate Rifampicin + isoniazid + pyrazinamide + ethambutol + steroids Amphotericin B
The MRI scan demonstrates a large multilobulated mass in the right frontal lobe. It homogeneously enhances and extends to involve the caudate and the periventricular area. There is also a significant mass effect. These findings in addition to the history are highly suggestive of primary CNS lymphoma. The most appropriate initial treatment is steroids (which should reduce tumour size and hence mass effect) and methotrexate. Other future options include whole brain irradiation and surgery.
You would not expect the enhancement to be homogenous with toxoplasmosis, it is usually in a ring pattern.
Primary CNS Lymphoma - Example Question
A 41-year-old man is admitted to the Emergency Department after having a seizure. He has no history of epilepsy but is known to be HIV positive. On examination he is still slightly confused post-ictally but there are no focal neurological signs. He is apyrexial and haemodynamically stable.
His current medications includes efavirenz, tenofovir, lamivudine and co-trimoxazole.
His latest CD4 count is 38 cells/µl.
CT scan (without contrast) is shown below:
SEE PASSMED PRIMARY CNS LYMPHOMA
What is the most likely diagnosis?
Cerebral toxoplasmosis Progressive multifocal leukoencephalopathy Cryptococcal infection > CNS lymphoma Cerebral tuberculosis
A hyper-attenuating mass adjacent to the left lateral ventricle is seen. The homogenous appearance, position and history (low CD4 count and current use of co-trimoxazole prophylaxis) are suggestive of primary CNS lymphoma rather than cerebral toxoplasmosis.
Cerebral Toxoplasmosis - Example Question
A 36 year old male Intravenous drug user presents to genito-urinary clinic. He was diagnosed with HIV 3 years ago after presenting with tuberculosis (TB). He was treated for TB for 6 months. He is now on third line anti-retroviral therapy for previous virological failure and co-trimoxazole. His most recent CD4 count was 104, and his viral load was 3,000 copies/ml.
He complains of weakness on his left side, and deterioration in vision, getting worse for four weeks. He has a moderately severe headache. On examination his visual acuity is 3/60 in his left eye and 6/6 in his right eye. He has weakness, in his left arm and leg, brisk reflexes and mildly increased tone.
He is immediately admitted.
A CT scan shows several ring enhancing lesions in his right cerebral hemispheres and one on the left cerebral hemisphere.
On ophthalmological review he has a large area of retinal necrosis in his left eye.
What is the diagnosis?
CNS lymphoma > Cerebral toxoplasmosis Cerebral TB Cerebral abscesses CNS Kaposi sarcoma
The most important three differential diagnosis for a ring-enhancing lesion in an HIV patient is CNS lymphoma, TB and Toxoplasmosis.
In this case the retinal necrosis in characteristic of ophthalmic toxomplasmosis. Multiple lesion also favour toxoplasmosis. His poor compliance with HIV treatment (as indicated by the low CD4 count and the high viral load) suggest his compliance with co-trimoxazole is also poo
