The document discusses various central nervous system manifestations that can occur in HIV/AIDS patients. It covers conditions such as HIV encephalopathy, cerebral toxoplasmosis, primary cerebral lymphoma, cryptococcosis, progressive multifocal leukoencephalopathy, tuberculosis, and aspergillosis. For each condition, it describes the clinical presentation, imaging findings on techniques such as CT, MRI, and spectroscopy, as well as treatment approaches.

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