1. CNS infection in HIV patients
Int.Naruenont Dolsaritchaiya th June 2013

2. Outline Approach Common diseases - basic knowledges
- medical treatment
- surgical indication
Take home messages

3. How to approach
HIV patients can acquire both opportunistic infections and others found in normal host
Work up should be extensive due to the possibility of multiple infections
However, opportunistic infection should draw attention firstly

4. How to approach
Algorithm

5. How to approach Source : HIV-associated Opportunistic
infections of the CNS
Lancet Neurol 2012;
11:

6. How to approach
Lesions can be categorized into 3 types based on radiological appearance :
1.Focal mass
2.White matter disease
3.Meningeal disease

7. How to approach Focal masses Focal masses with rim-enhancement
1.Toxoplasmosis
2.Tuberculoma
3.Cryptococcoma
4.Primary CNS lymphoma (not infection)
5.Bacterial and fungal abscesses
6.CMV encephalitis (rarely)

8. How to approach Focal masses Focal masses without rim-enhancement
1.Toxoplasmosis
2.Cryptococcoma
3.Atypical primary CNS lymphoma

9. How to approach White matter disease 1.HIV encephalopathy (HIVE)
2.CMV encephalitis
3.Progressive multifocal leukoencephalopathy (PML)

10. How to approach Meningeal disease 1.HIV meningoencephalitis
2.Cryptococcal meningitis
3.Tuberculous meningitis
4.Other bacterial/viral meningitis

11. Common diseases

12. Toxoplasmosis Principal OI in HIV patients 15-40% of AIDS patients
Usually occurs when CD4 < 100
Almost always a reactivation and serology is positive in 85%
Seronegative cases occur as a result immunosuppression or rarely a primary infection

13. Toxoplasmosis Common sites : 1.Basal ganglia
2.Cortico-medullary junction
usually frontal and parietal lobe
3.Brainstem
Meningeal involvement uncommon

14. Toxoplasmosis Diagnosis 1. Imaging : CT/MRI - rim-enhancing lesion
- typically 1-2 cm
- < 20% solitary
2.Serology : IgG, IgM
3.PCR

15. Toxoplasmosis

16. Toxoplasmosis Treatment : Pyrimethamine + Sulfadiazine 6 weeks
In cases of failure to diagnose or respond to medical treatment within 7 days, biopsy is needed for tissue pathological diagnosis
Secondary prophylaxis until CD4 > 200 for 6 months

17. Tuberculosis Found in both immunocompromised and immunocompetent host
HIV patients are prone to develop reactivation and extrapulmonary infection
Tuberculous meningitis and tuberculoma/TB abscess (uncommon)

18. Tuberculosis CN III palsy
Involves cerebral artery which can produce focal ischemia

19. Tuberculosis Diagnosis 1.CSF profile : mainstay for Dx
***AFB +ve in 1/3
2.Imaging : CT/MRI

20. Tuberculosis
Diagnosis : CSF profile

21. Tuberculosis Imaging : CT/MRI
- Leptomeningeal enhancement mainly at the base of skull
- tuberculoma at basal ganglia
- communicating/noncommunicating hydrocephalus

22. Tuberculosis
Imaging : CT/MRI

23. Tuberculosis Treatment : HRZE x 9 months or more
***Steroid reduces morbidity
In case of hydrocephalus, extraventricular drainage or shunt is required to reduce ICP

24. Cryptococcosis Usually develops when CD4 < 100
Forms : meningitis/cryptococcoma
pulmonary
skin and soft tissue
Meningismus may be absent
Complication : CN deficit, visual loss, cognitive impairment

25. Cryptococcosis Poor prognosis : - +ve Indian ink - high CSF pressure
- low glucose
- low pleocytosis < 2 cells/mm3
- extraneural yeast cell
- absence of Ab
- CSF or serum crypto. Ag > 1:32
- steroid use
- hematologic malignacy

26. Cryptococcosis Diagnosis 1.Indian ink 2.Cryptococcal Ag in CSF/serum
3.Imaging : CT/MRI

27. Cryptococcosis

28. Cryptococcosis Imaging : CT/MRI - hydrocephalus
- meningeal enhancement
- cryptococcomas at basal ganglion
- punched-out cystic lesion

29. Cryptococcosis
Imaging : CT/MRI

30. Cryptococcosis Treatment :
Amp. B mg/kg/day 2 weeks and then fluconazole 400 mg/day for 10 weeks
Repeated LP or shunt is necessary to relieve increased ICP
Secondary prophylaxis until CD4 > 200 for 6 months

31. Primary CNS lymphoma
Frequently occurs in severe immunosuppression or AIDS
High grade B-cell lymphoma
Strongly associated with EBV
Poor prognosis compared to similar lymphoma outside CNS

32. Primary CNS lymphoma Imaging : CT/MRI
- rim-enhancing or heterogeneously enhancing
- usually > 3 cm
- periventricular, frontal, temporal
Difficult to distinguish from toxoplasmosis or metastasis

33. Primary CNS lymphoma
Diagnosis usually made after failure to respond to toxoplasmosis Rx
Brain biopsy is mandatory to obtain tissue pathology
If safe to LP, CSF for EBV DNA help to diagnose with no need to perform biopsy

34. Primary CNS lymphoma
Imaging : CT/MRI

35. Primary CNS lymphoma Treatment : CMT + WBRT
> 90% have a recurrence disease
Surgical resection : for immediate decompresion of life-threatening mass effect

36. HIV encephalopathy HIV-associated dementia
Symptoms : progressive dementia, cognitive impairment, motor symptoms, gait disturbance, tremor
Subcortical dementia : no aphasia, apraxia or agnosia
Alertness is minimally perturbed

37. HIV encephalopathy
Diagnosis
1.Imaging : CT/MRI
2.CSF profile

38. HIV encephalopathy
Imaging : CT/MRI

39. HIV encephalopathy CSF profile
- non specific increased in cells and protein
- helpful in diagnosing or ruling out OI
- HIV RNA not correlate with HIV encephalopathy

40. HIV encephalopathy
Treatment : HAART
CNS resistance may occur

41. CMV encephalitis Usually occurs when CD4 < 50
Reactivation of latent infection
Two forms :
1.Encephalitis : progressive dementia
2.Ventriculoencephalitis : CN deficit, alteration of consciousness, nystagmus, disorientation, ventriculomegaly

42. CMV encephalitis Diagnosis 1.CSF : PCR for CMV DNA culture
2.Imaging : CT/MRI
- periventricular enhancement
***no calcification like congenital CMV
- subependymal enhancement
- 50% normal imaging

43. CMV encephalitis
Imaging : CT/MRI

44. CMV encephalitis Treatment : Ganciclovir, Valganciclovir
induction of days followed by prolonged maintenance therapy
Secondary prophylaxis until CD4 > 100 for 3 months

45. PML Caused by the reactivation of the Jamestown Canyon (JC) virus
CD4 counts usually below 100/mm3
Multiple areas of demyelination throughout the brain sparing cord and optic nerve

46. PML
Symptoms : visual loss
mental impairment
weakness
ataxia

47. PML Diagnosis : 1. MRI - multifocal asymmetric white matter lesions
- subcortical white matter, cerebellum
- low signal on T1 weighted images and hyperintense on T2 weighted/FLAIR

48. PML
Diagnosis : MRI

49. PML
Diagnosis :
2.CSF : PCR for JCV DNA
normal cells and protein

50. HSV encephalitis HSV produces necrotizing encephalitis in HIV patients
Predilection for the medial temporal and inferior frontal lobes

51. HSV encephalitis Diagnosis : 1.CSF : PCR for HSV DNA
- sens. 96% and spec. 99%
(equivalent or exceed brain biopsy)
- maybe negative if too early (< 72 hr) or more than 14 days

52. HSV encephalitis Diagnosis : 2.Imaging : CT/MRI
- area of low absorption, mass effect or hemorrhage on CT
- hyperintensity signal on T2/FLAIR or diffuse-weighted

53. HSV encephalitis
Imaging : CT/MRI

54. HSV encephalitis
Treatment : IV acyclovir 10 mg/kg q 8 hr for 14 days and repeat CSF profile
*** Dilute < 7mg/ml and infused slowly over 1 hr to minimize renal dysfunction

55. Take home messages
Neurological manifestations in HIV/AIDS patients have a wide spectrum
Clinicians must consider multiple causes which share similar clinical and radiographic patterns
Neurosurgery carry an important role for diagnosis and treatment

56. References Youman textbook of neurosurgery 6th ed.
Harrison textbook of internal medicine 17th ed.
Lancet neurology 2012

57. THANK YOU