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CNS IMMUNE RECONSTITUTION Role of Magnetic
Resonance Imaging in Disease Definition
Simonetta Gerevini MD Neuroradiology
Department San Raffaele Hospital, Milan, Italy
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Definition criteria for IRIS

• HIV positive
• Receiving HAART
• Decrease in HIV-1 RNA level
• Increase in CD4 cells
• Clinical symptoms consistent with inflammatory
  process
• Clinical course not consistent with
• Previously or newly diagnosed OI
• Drug toxicity

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IRIS CNS manifestation

• Infrequently reported
• Cases observed in the context of known CNS
  infections
• - CNS cryptococcosis
• - progressive multifocal leukoencephalopathy
  (PML)
• CNS mycobacteriosis
• HSV, VZV, CMV encephalitis
• Cases associated with no infectious agent

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IRIS with Cryptoccal Meningitis

• usually not detected at MRI (pachymeningeal
  enhancement)
• occasional intracerebral enhancing mass lesions

Lortholarya et al. AIDS 2005
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PML in IRIS
MRI may show contrast enhancement at lesions
periphery Marker of improved immune status
usually associated with good outcome (but in
rare instances coincided with clinical and
radiological deterioration)
Hoffmann et al, J. Neurol. Neurosurg. Psychiatry
2003
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PML in IRIS
Onset
1 month after initiation of HAART
Vendrely A et al. Acta Neuropathol 2005
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Severe HIV-1 leukoencephalopathy in subjects
failing HAART
Langford D et al., AIDS 2002
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IRIS as Diffuse leukoencephalopathy after HAART
R F. Miller, Acta Neuropathol 2004
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IRIS as Cerebral vasculitis
Van der Ven, AIDS Vol 16(17) 2002
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Systematic review of IRIS

• Time period 1998-2006
• Definition criteria as for systemic IRIS
• 380 pts with MRI to investigate CNS symptoms
• PML 17 cases
• Crypto 1 cases
• VZV 2 cases
• HIV 1 case
• Apparently no associated infections 11 cases

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Objective

• To use MRI to recognize, describe and classify
• CNS IRIS focusing on lesions with no apparent
• associated pathogens

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MRI findings
Diffuse leukoencephalopathy Without
Enhancement 3 cases
Focal or extensive lesions Enhancement
(vasculitis-like lesions) 8 cases
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Summary of Patient findings
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Vasculitis like lesions Case 3.
A. Acute (November 2001)
T2
T1-G
F
Sept 2001 AZT,3TC,LPV/r
Nov 2001 SIR-SNC
300
6
HAART
CS
250
5
200
4
B. Follow-up (June 2002)
150
3
T2
T1-G
F
Log10 HIV-RNA copies/mL
CD4 cell/mmc
100
2
50
1
0
0
1
6
12
18
Months
C. Today (June 2006)
T2
F
T1-G
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Vasculitis like lesions Case 8.
Jan 2007
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PML in IRIS Case 7.
March 06
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Vasculitis like lesionsCase 7.
March 06
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Diffuse Leukoencephalopathy Case 2.
A. Acute (March 2002)
T2
T1
June 2001 3TC,IDV,RTV
March 2002 SIR-SNC
600
5
HAART
500
4
400
3
300
B. Follow-up (July 2003)
2
CD4 cell/mmc
200
Log10 HIV-RNA copie/mL
1
T2
T1
100
0
0
1
6
12
18
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Months
C. Today (June 2006)
T1
T2
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Diffuse Leukoencephalopathy Case 1.
A. Acute (Feb 2002)
T2
T1-G
T1
February 2002 SIR-SNC
August 2001 3TC,d4T,IDV/r
250
5
HAART
200
4
8185
150
3
Log10 HIV-RNA copie/mL
CD4 cell/mmc
100
2
105
50
1
B. Follow-up (May 2002)
0
0
0
6
12
18
Months
T2
T1-G
T1
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Possible interpretation open questions
White matter signal alteration at MRI
Demyelination (extensive)? Inflammation
(focal)? Cell toxicity? White matter signal
alteration and contrast enhancement Unspecific
inflammation ? Specific response to infectious
agent or antigen ?
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Conclusions

• MRI is essential for diagnosis and monitoring of
  CNS
• IRIS
• Future studies are expected to
• estabilish prevalence and incidence of CNS IRIS
• provide guidelines for diagnosis and clinical
  management
• better understand the underlying mechanism

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Thank you for your attention
Corrisponding address gerevini.simonetta_at_hsr.it
Special thanks to P.Cinque, A.Boschini,
P.Vezzulli, S.Bossolasco and A.Pazzi