CNS Manifestations in HIV

1. CNS manifestations in HIV
17-02-2016
Dr. Y. Madhu Madhava Reddy

2. 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.

3. CNS disease in HIV / AIDS

4. 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.

5. 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.

6. HIV encephalopathy

7. HIV encephalopathy

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. Cerebral Toxoplasmosis

16. Coexisting Toxoplasmosis & Lymphoma

17. Cerebral Toxoplasmosis

18. 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.

19. 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.

20. 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%.

21. 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.

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

23. Multifocal Primary Cerebral lymphoma

24. Primary Cerebral lymphoma

25. 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.

26. Primary Vs Secondary Lymphoma
• Metastases from systemic lymphoma
typically involve the meninges; parenchymal
disease without leptomeningeal involvement
is rare.

27. Primary Cerebral lymphoma
• Treatment: lymphoma dramatically respond
to radiotheraphy and or corticosteroids.
• Poor prognosis. HAART has prolonged
median survival from 2 – 8 months.

28. 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.

29. 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.

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

31. Cryptococcomas

32. 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.

33. 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.

34. 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.

35. 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.

36. PML

37. PML

38. 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%.

39. 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.

40. 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.

41. Tuberculous meningitis

42. 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 ).

43. 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

44. CNS TB

45. CNS TB
• Tuberculous meningitis is most lethal
infection associated with CNS TB- 30%
mortality.
• Treatment: Steroids + ATT.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.

51. 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.

52. Disseminated Aspergillosis

53. 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.

54. Herpes simplex ventriculitis

55. 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.

56. Neurosyphilis

57. 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.

58. 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.

59. 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.

60. 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.

61. 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.

62. 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).

63. 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.

64. 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.

65. IRIS

66. 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.

67. 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.

68. 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

69. Thank You