CNS infections in HIV

CNS manifestations in HIV

17-02-2016Dr. Y. Madhu Madhava Reddy

Introduction

• After the lung, the central nervous system (CNS) is the organ most frequently affected by the human immunodeficiency virus (HIV).

• Post mortem studies show upto 70% of patients with HIV has CNS abnormalities.

• Neurological symptoms in HIV occur because of Oppurtunistic Infections, effects of HIV itself and adverse effects of theraphy.

CNS disease in HIV / AIDS

HIV encephalopathy

• Aka HIV-associated cognitive-motor complex, HIV- associated dementia.

• Presents with cognitive impairment and motor symptoms.

• Prevalence : 1- 20% of AIDS cases.• Incidence have been decreased with

introduction of HAART.

Imaging findings

• Commonest imaging finding is Cerebral atrophy, the extent of volume loss correlates with cognitive impairment.

• White matter lesions in centrum semiovale and periventicular regions ( Low attenuation on CT and T2 prolongation on MRI, which lack mass effect and don’t enhance).

• WM changes progress with time, become diffuse and confluent.

HIV encephalopathy

HIV encephalopathy

Important feature

• HIV encephalopathy does not result in mass effect or enhancement. If either of these findings is present, another diagnosis must be considered.

• Patients receiving HAART may show stabilization or even regression of MRI abnormalities. Early follow-up imaging may show lesion progression but this is not indicative of treatment failure.

MR Spectroscopy

• Decreased N-acetyl aspartate (NAA) – because of neuronal loss.

• Increased Choline – marker of membrane turnover

• Increase Myoinositol – a glial cell marker.• These findings are detected before the MRI

features appear.• These MRS findings can be reversed with

HAART.

PET and SPECT

• May show hypermetabolism in basal ganglia and thalami in patients with normal MRI.

• Although the sensitivity of these techniques is high, the specificity is undetermined and the role in clinical practice is not established.

DTI

• DTI shows reduced whole-brain fractional anisotropy (FA) in cognitively impaired HIV-infected patients. The reduction in FA correlates with the severity of cognitive impairment.

Cerebral Toxoplasmosis

• It is the commonest cause of mass lesion in AIDS and is also the most treatable.

• It results from reactivation of latent infection by Toxoplasma gondii.

• Patients present with headache, fever, confusion, personality change and focal neurological deficit.

Imaging findings

• Multiple lesions, 1-4cms across at the corticomedullary junction and in basal ganglia.

• Lesions show ring or nodular enhancement with associated oedema and mass effect. They can haemorrhage.

• Enhancement is diminished or absent in severely immunocompromised patients.

• Main differential diagnosis is Primary CNS lymphoma, which appear identical and can coexist in same patient.

Imaging findings

• Single lesions and lesion in brain stem or cerebellum are uncommon.

• NECT show multiple areas of abnormal low attenuation, they demonstrate ring or nodular enhancement on postcontrast CT images.

Cerebral Toxoplasmosis

Coexisting Toxoplasmosis & Lymphoma

Cerebral Toxoplasmosis

Imaging features

• DWI: In comparison to pyogenic abscesses cerebral toxoplasmosis is hypointense to white matter on DWI, indicating no restriction of diffusion.

• MRS: Elevated lipid – lactate peaks.• Treatment is with pyrimethamine and

sulfadiazine. Most lesions show reduced enhancement, oedema and mass effect within 2-4 weeks.

Primary Cerebral Lymphoma

• It is the AIDS-defining diagnosis and it occurs in 5% of patients.

• Incidence has reduced in era of HAART.• Patients present with rapid progression of

confusion, lethargy, memory loss and focal neurology.

Imaging findings

• Cerebral lymphoma is often multifocal in AIDS.

• Lesions are commonest in cerebral WM and also in basal gangia, corpus callosum and ventricular margins.

• Lesions abutt the ependyma, leptomeninges or both in 75%.

Imaging findings

• Imaging shows well-defined round or oval lesions of high attenuation on unenhanced CT, and lower signal intensity than grey matter on T2W MRI.

• This reflects the dense cellularity of lymphoma. • Lesions have relatively little mass effect and

oedema for their size.• Heamorrhage is unusual and calcifications seen

only after treatment.

Imaging findings

• Enhancement is typical in a smooth or nodular ring surrounding a zone of central necrosis.

Multifocal Primary Cerebral lymphoma

Primary Cerebral lymphoma

Lymphoma Vs Toxoplasmosis

• Single enhancing mass lesions in AIDS is more likely to be Lymphoma.

• Sub ependymal spread is a feature of lymphoma.

• Thallium-201 SPECT and FDG-PET show greater uptake in lymphoma than toxoplasmosis.

• DWI has limited value.

Primary Vs Secondary Lymphoma

• Metastases from systemic lymphoma typically involve the meninges; parenchymal disease without leptomeningeal involvement is rare.

Primary Cerebral lymphoma

• Treatment: lymphoma dramatically respond to radiotheraphy and or corticosteroids.

• Poor prognosis. HAART has prolonged median survival from 2 – 8 months.

Cryptococcosis

• This is the second commonest opportunistic CNS infection in AIDS.

• Patients most often present with headache, fever and altered mental state.

• The earliest imaging manifestation is dilatation of perivascular spaces due to mucoid material, organisms and inflammatory cells and appear as multiple small foci of high signal on T2W.

Cryptococcosis

• With disease progression cryptococcomas develop at these sites, forming lesions 3 mm to several cms in size.

• Most often in the basal ganglia but also in the brainstem and cerebral white matter.

• Enhancement of cryptococcomas or leptomeninges is rare as these patients are profoundly immunocompromised.

Cryptococcosis

• It spreads to CNS hematogenously from a pulmonary focus; however reactivation of latent infection is also possible.

Cryptococcomas

DD’s

• Main differential diagnoses for an enhancing lesion in basal ganglia are lymphoma, toxoplasmosis.

• Treatment: fluconazole and amphotericin B• Without treatment the infection is fatal.• Complications: Hydrocephalus, seizures,

dementia and motor and sensory deficits.

Progressive multifocal leukoencephalopathy

• PML is a central demyelinating disease resulting from the reactivation of a latent infection of oligodendrocytes by JC polyomavirus.

• Incidence : 4-5% of AIDS patients.• Clinically, limb weakness is commonest

presentation, visual field defects, speech abnormalities, ataxia and dementia may be seen.

PML imaging findings

• Lesions can occur in any part of brain but are commonest in parieto-occipital regions.

• MRI shows multifocal, asymmetric bilateral white matter lesions that are of high signal on T2W and low signal on T1W images.

• Extension to the subcortical U-fibres gives the lesions a characteristic ‘scalloped’ appearance.

PML Imaging findings

• CT reveals asymmetric focal zones of low attenuation that involve the periventricular and subcortical white matter.

• This appearance is a differential diagnostic feature compared with the typically more symmetric areas of low attention seen in patients with HIV encephalopathy.

• They don’t enhance and haemorrhage is unusual.

PML

PML

Tuberculosis

• CNS TB is an AIDS defining illness, and may be initial clinical manifestation of AIDS.

• It can result from reactivation of a previous infection, spread from a primary or a newly acquired infection. (Spreads mainly hem route)

• Incidence: 5-9% of AIDS pts dev. TB of which 2-18% will have CNS infection.

• It has high mortality rate of 70%.• CXR will be positive in 65%.

Imaging features

• Most common intracranial manifestation of TB is meningitis; more prominent in basal cisterns esp. around Circle of willis.

• Tuberculomas, tuberculous abscess and cerebral ischemia and infarction are not uncommon.

• On imaging, meningeal enhancement (45%), hydrocephalus(51%). Hydrocephalus is due to obstruction of basal cistern by exudates.

Tuberculous meningitis

• Cerebral abscess and tuberculomas may be seen.• Tuberculomas and granulomas results either

from hematogenous spread or extension from CSF infection via cortical veins or small penetrating arteries.

• Location: majority are supratentorial ( solitary or multiple), however they are found in subdural, epidural and Subarachnoid spaces.

Tuberculous meningitis

Imaging findings

• MRI: Tuberculomas are hypointense on T2WI in early stages; as they mature, they develop a hypointense center surrounded by an isointense capsule, which corresponds to solid caseation necrosis.

• They may further progress to abscess formation with hyperintense centre.

• Post contrast images: Granulomas show Nodular homogenous enhancement ( non caseating ) / ring enhancement ( caseating ).

Imaging findings

• Associated findings in TB are hydrocephalus, basal ganglia infarction and cisternal enhancement.

• Presence of these findings should help to distinguish from lymphoma and toxoplasmosis

CNS TB

CNS TB

• Tuberculous meningitis is most lethal infection associated with CNS TB- 30% mortality.

• Treatment: Steroids + ATT.

Aspergillosis

• It occurs via hematogenous spread from pulmonary focus, or fungus may directly invade the brain via the sinus.

• A resultant vasculopathy may cause acute infarction or hemorrhage, or fungus can extend into surrounding tissue, resulting in an infectious cerebritis or abscess.

• Aspergillus has predisposition to infect perforating arteries.

Aspergillosis

• Involvement of skull base and oribit leads to visual disturbances and cranial palsies and invasive sinonasal infections are lethal in greater than 50% of cases.

Aspergillosis

• Aspergillus invades blood vessles and spread along the internal elastica and lamina, resulting in vascular thrombosis and hemorrhagic infacts with variable inflammation.

• Typically, dissemination leads to multiple intra parenchymal lesions, often in MCA distribution.

Imaging findings

• Three patterns:• A) multiple cortical and subcortical regions of

low attenuation on CT images, with T2 hyperintensity seen in corresponding areas on MRI.

• B) multiple ring-enhancing lesions• C) dural enhancement adjacent to enhancing

lesions of paranasal sinuses or calvaria.

Imaging findings

• The presence of hemorrhage associated with the lesions and intraparenchymal hemorrhage in an immunocompromised patient should cause one to consider the possibility of aspergillosis.

• The ring enhancement may be subtle or well defined, which may be related to the patient’s immune status.

Aspergillosis

• Lesions of corpus callosum, basal ganglia, and thalami may be seen, because of perforating arteries.

• Treatment and prognosis: Fatality rate is reported to as high as 88%.

• Treatment is limited and care is taken for prevention of infection.

Disseminated Aspergillosis

Herpes Virus

• Cytomegalovirus, herpes simplex and varicella zoster viruses can cause encephalitis, necrotizing ventriculitis , and myelitis in AIDS.

• In encephalitis imaging may be normal, show nonspecific white matter lesions or focal enhancing lesions.

• Ependymal enhancement occurs with ventriculitis; myelitis manifests as nonspecific swelling and signal change in the spinal cord.

Herpes simplex ventriculitis

Neurosyphilis

• CNS involvement can occur at any stage of syphilis, in HIV-infection its course may be more aggressive.

• Meningovascular syphilis causes a small-vessel endarteritis that appears as arterial segmental ‘beading’ on angiography, with associated infarcts in the basal ganglia.

• Cerebral gummas are rare, typically arise from the meninges, and appear as mass lesions with variable MR signal characteristics and enhancement.

Neurosyphilis

Candidiasis

• Although mucocutaneous candidiasis is common in HIV-infected patients, CNS involvement is rare.

• Haematogenous dissemination results in meningitis and/or cerebral abscesses.

• Imaging appearances are nonspecific; clinical confirmation is dependent on CSF analysis or brain biopsy.

Incidental WM hyperintensities

• Focal white-matter hyperintensities, often multiple, are seen in up to 26 per cent of HIV-positive patients and up to 24 per cent of seronegative men of matched ages.

• No associations with neurological abnormalities, CD4 count, or vascular risk factors have been identified. These lesions are probably incidental and of no clinical significance.

Histoplasmosis

• Histoplasmosis occurs in up to 5 per cent of AIDS patients in areas where Histoplasma capsulatum is endemic.

• CNS manifestations include meningitis with involvement of adjacent vessels, and single or multiple abscesses.

• Imaging may show meningeal enhancement, cerebral infarcts, or focal enhancing lesions with mass effect and oedema.

Cerebrovascular disease

• Cerebral infarcts occur in fewer than 5 per cent of AIDS patients. Causes include infective vasculitis (CMV, varicella zoster or tuberculosis) and embolism from HIV cardiomyopathy.

• HIV also causes a dilating vasculopathy that results in fusiform aneurysms of the intracranial vessels.

Spinal cord disorders

• AIDS-associated vacuolar myelopathy presents insidiously and progresses to severe paraparesis.

• Thoracic cord is most commonly affected.• MRI ususally normal or shows nonspecific

changes such as diffuse symmetrical signal abnormalities in the cord.

• Other diseases affecting cord in AIDS are herpes, toxoplasmosis and tuberculosis.

Immune reconstitution Inflammatory syndrome (IRIS)

• HAART succeeds in suppressing HIV replication and improving cellular immunity, which protects HIV-infected patients against opportunistic infections.

• However, in a few of these patients, partial restoration of specific immunity may worsen a preexisting disease; the resulting condition is referred to as immune reconstitution inflammatory syndrome (IRIS).

IRIS

• IRIS is not caused by a relapse or recurrence of the preexisting disease, and its exact etiology is unknown.

• IRIS is thought to be related to reconstitution of immunity, which leads to abnormal immune response to either specific infectious or noninfectious antigens.

IRIS

• Patients with IRIS demonstrate paradoxic deterioration in their clinical status when their CD4 counts rise and viral replication appears to be under control , and death from IRIS has been reported .

• IRIS occurs in the initial months after the onset of HAART.

• The neuroimaging findings vary, depending on the underlying pathologic conditions, and may be atypical, such as prominent, progressive enhancement and mass effect seen in PML.

IRIS

Conclusion

• The neuroimaging findings of infectious CNS diseases in patients with HIV infection are varied, including mass lesions, atrophy, demyelination, vascular complications, and meningoencephalitis.

• HAART has led to improvement of many of the imaging findings as the patients survive for a long time, but it can occasionally result in IRIS, which has atypical imaging findings.

Conclusion

• Knowledge of the imaging findings of infectious CNS diseases in HIV-infected patients, as well as the impact of HAART, is important in patient treatment.

References

• Adam Grainger & Allison’s Diagnostic radiology 5th Edition

• RSNA journal - Central Nervous System Infections Associated with Human Immunodeficiency Virus Infection http:// www.rsna.org /education /rg_cme.html

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