HIV and CNS Stereotactic Biopsy in the diagnosis of brain lesions in AIDS patients
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1 HIV and CNS Stereotactic Biopsy in the diagnosis of brain lesions in AIDS patients Department of Neurosurgery Infectious Diseases Hospital, University of Buenos Aires, Argentina
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3 Definition AIDS Patients - Patients with high life risk due to HIV infection - Asociated pathologies or systemic diseases caused by the HIV Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
4 Classification of patients infected with HIV-1 Clinical Subgroups A : Acute infection/ Asymptomatic HIV+ patient B : Symptomatic patients not included in A or C (oropharingeal or vulvovaginal candidiasis, cervical dysplasia or in situ carcinoma, peripheric neuropathy, LOV,VHZ,PTI, pelvic inflamation disease) C : Markers diseases of AIDS
5 Classification of patients infected with HIV-1 Clinical Subgroups CD4 LEVELS A B C > 500/mm A1 B1 C /mm A2 B2 C2 < 200/mm A3 B3 C3 Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
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7 Neurologic Symptoms in AIDS 50% develop neurologic symptoms 10% present initially with neurologic complaint 10-20% normal brain on autopsy Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
8 Neurological symptoms are very often found in HIV AIDS disease and it usually has a very high morbidity and mortality It appears in any stage of the disease Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
9 CNS involvement First stage or Acute Retroviral Syndrome - aseptic meningitis, seroconversion acute mielitis, peripheral neuropathies, Guillain- Barré S. Middle or chronic stage : Immune mediated neuropathies, Antiretroviral toxicity Final stage or AIDS : CNS infections CNS tumors Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
10 CNS infections PARASITIC INFECTIONS Toxoplasmosis Trypanosomiasis FUNGAL INFECTIONS : Criptococcosis Candidiasis Aspergillosis Histoplasmosis BACTERIAL INFECTIONS : Tuberculosis Micoabacterium a.i. Treponema Bacterial infections VIRAL INFECTIONS : CMV PML/JCV HSV VZV
11 CNS tumors Primary CNS Lymphoma Secondary Lymphoma Kaposi Sarcoma Gliomas?? Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
12 Mechanism of action of HIV-1 Direct Mechanism HIV infection of cells Indirect Mechanism Toxic effect of HIV-1 proteins over neuronal tissue Interaction between glial cells and infected macrophages result in neuronal damage NMDA receptor associated with neuronal damage
13 HIV-CNS-Pathophysiology Gonzalez-Scarano F et al. Nat Rev Immunol 2005;5:69-81
14 HIV-SNC-Pathophysiology Gonzalez-Scarano F et al. Nat Rev Immunol 2005;5:69-81
15 Diagnostic Algorithm NEUROLOGICAL CT / MRI NORMAL ABNORMAL CSF/SEROLOGY ABNORMALITIES/NO MASS LESION CSF/SEROLOGY SINGLE MULTIPLE POSITIVE/JCV/CRIPTO NEGATIVE TOXO TREATMENT? TOXO TREATMENT TREATMENT BIOPSY NO RESPONSE RESPONSE BIOPSY
16 Stereotactic brain biopsy Minimal Invasive Procedure Maximal efficacy Minimal morbidity
17 Stereotactic brain biopsy When? What for? How? Results Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
18 Stereotactic brain biopsy When? What for? How? Results Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
19 Stereotactic brain biopsy When? What for? How? Results Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
20 Stereotactic brain biopsy When? What for? How? Results Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
21 Stereotactic brain biopsy First step : frame Second step : image aquisition (CT, MRI). Third stepo : planning. Forth step : biopsy
22 Frame
23 Image aquisition
24 Planning Claudio G. Yampolsky M.D
25 Biopsy
26 Claudio G. Yampolsky M.D
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28 Claudio G. Yampolsky M.D
29 Is the biopsy representative of the lesion???
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31 Diagnostic yield Intraoperative: sensitivity 78%; specificity 90% Cytology: sensitivity 88% specificity 90%
32 STEREOTACTIC BIOPSY IN AIDS PATIENTS (N = 300) PCNSL PML TOXO CHAGAS ENCEPHALITIS CRIPTO TBC
33 STEREOTACTIC BIOPSY IN AIDS PATIENTS (N = 300) PML CNSL Toxoplasmosis Chagas Vasculitis TBC VIH ENC Cripto
34 Diagnosis N=300 PCNSL...88 (29,3%) PML...69 (23%) TOXOPLASMOSIS (15,3%) CHAGAS DISEASE...16 (5,3%) TUBERCULOSIS (4%) ENCEPHALITIS-VIH (4%) CRIPTOCOCOMA (2,7%)
35 Diagnosis N=300 VASCULITIS...6 (2%) NOCARDIOSIS...3 (1%) HISTOPLASMOSIS (0.3%) PML VZV+JCV...1 (0.3%) GRANULOMA...1 (0.3%) ENCEPHALITIS VIH+VZV (0.3%)
36 Diagnosis N=300 ASTROCYTOMA G IV...5 (1,7%) GLIOSARCOMA. 1 (0,3%) OLIGODENDROGLIOMA (0,7%) HODGKIN LYMPHOMA (0,3%) BRAIN STEM MTS (0,7%) INCHARACTERISTICS FINDINGS..25 (8.3%)
37 CNS lymphoma High incidence ( 1 a 10-12%) Most frequent non infectious disease found on AIDS patients Incidence: 2.7% in clinical series and 1-15% in autopsies Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
38 CNS lymphoma Related with immunosupression High grade, difuse B- cells Tumors Multiple and bilateral Related with Epstein Barr Virus Single periventricular lesions Multiple infra and supratentorial lesions MRI Spectroscopy : high coline, low NAA and presence of fat and lactate Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
39 35 years old male, headaches and seizures CD4 < 50 cells Claudio G. Yampolsky M.D
40 28 years old male, right hemiparesia and seizures CD4 < 50 cells Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
41 25 years old female, seizures and headaches CD4 < 50 cells Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
42 CNS lymphoma Claudio G. Yampolsky M.D
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44 CNS lymphoma Claudio Claudio G. Yampolsky G. Yampolsky M.D. M.D.
45 CNS lymphoma
46 CNS lymphoma
47 CNS lymphoma -Lymphoid cells in the perivascular space -
48
49
50 CD 20
51 GFAP
52 bp 500 bp 108 bp 100 bp PCR- Epstein Barr
53 - Circulating Epstein-Barr virus (EBV) in HIV-infected patients and its relation with primary brain lymphoma International Journal of Infectious Diseases 11, (2007) - Epstein-Barr virus genotypes and LMP-1 variants in HIV infected patients Journal of Medical Virology 79: (2007)
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55 TOXOPLASMOSIS 47 years old male, headaches and focal symptoms, CD4 < 50 cells
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57
58
59
60 Chagas disease Meningoencephalitis Brain Chagomas
61 32 years old male, headaches and left hemiparesia, CD4 < 50 cells
62 24 years old male, headaches. CD4 < 50 cells
63 55 years old male. seizures CD 4 < 50 cells
64 Chagas disease
65 Chagas disease
66 Chagas disease
67 Chagas disease
68
69 Chagas disease
70 Chagas disease
71 Chagas disease
72
73
74 Chagas disease Trypanosoma in blood and CSF samples
75 Chagas disease Meningoencephalitis with free amastigotes in brain smear, Anti-chagas policlonal antibody immunoreactivity. 400 X
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77 Tuberculosis Meningoencephalitis Brain Tuberculomas Brain Abscess Vasculitis
78 Tuberculosis
79
80 Tuberculosis
81 Tuberculosis
82 Tuberculosis Vasculitis
83 Criptococcosis Meningoencephalitis Criptococcomas Soap bubble lesions
84 Criptococcosis
85 CRIPTOCOCOSIS
86 Nocardia
87 Nocardia Absesus
88 Gliosarcoma
89 1 2 3 Fig. 1: Fusocelullar Tumor with mitosis. HE 200 X Fig. 2: Fusocelullar Tumor, positive immunomarcation for Vimentine. 400 X Fig. 3: Fusocelullar Tumor, negative immunomarcation for GFAP. 400 X
90 Oligodendroglioma
91 Brain stem metastasis
92 Progressive Multifocal Leukoencephalopaty ( JCV )
93 PML
94 PML
95
96 PML
97 PML :Cell with an intranuclear inclution body. inclution in EPON X
98 PML ( JCV + VZ )
99 PML ( JCV + VZ )
100 PML( JCV + VZ )
101 PML( JCV + VZ )
102 STEREOTACTIC BIOPSY IN AIDS PATIENTS (N = 300) contrast enhancement no enhancement 37% 63%
103 BIOPSIAS ESTEREOTÁCTICAS EN PACIENTES HIV + (N = 262) Lesiones que captan contraste (N = 161) 26% 3% 2% 4% 4% 1% Linfoma Chagas Toxoplasmosis Mts. Ca. Gliomas INC Cripto TBC 9% 51%
104 BIOPSIAS ESTEREOTÁCTICAS EN PACIENTES HIV + (N = 262) Lesiones que no captan contraste (N = 101) ENCEFALITIS 13% TOXO 6% GLIOSIS 17% LINFOMA 2% LMP 61%
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106 Complications (N=300) Morbility : 5 patients (1,7 %) Mortality : 2 patients (0,7%)
107 Results (N=300) Over 300 procedures we arrived to a diagnosis (histology/bacteriology/virology) in 275 patients DIAGNOSTIC YIELD : 91,7%
108 Conclusions Neuroradiology, as well as serologic, or csf analysis are useful but they cannot make a patognomonic diagnosis Antiretroviral treatment can be started if you find desmielinization in MRI with JCV in CSF (PML) AIDS patients with CNS lesion, atypical for toxoplasmosis or with bad response to anti toxo treatment are suitables for a stereotactic biopsy Cooperation among different medical disciplines lead to a better diagnose and prognostic for those patients
109 Thank you
110 SEE YOU IN ARGENTINA!
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