This document summarizes various neurological complications of HIV/AIDS, including: - Acute retroviral syndrome occurring in the majority after initial HIV exposure, potentially causing meningitis. - HIV-associated encephalopathy, the most common HIV-related brain disease, presenting as cognitive and motor slowing. - Myelopathy, characterized by vacuolar changes in the thoracic spinal cord causing spasticity and sensory symptoms. - Several types of infections are described like toxoplasmosis, cryptococcus, CMV, and various types of mycobacteria. - Primary central nervous system lymphoma is an AIDS-defining cancer that can involve the brain, eyes and spinal fluid. - Neurotoxic

1. Acquired immune
deficiency syndrome
Youmans Chapter 45

2. Outline
• HIV infection of the nervous system
• AIDS-related malignancies
• Infection
• HIV treatment-related neurotoxicities

3. • Acute retroviral syndrome
• HIV-associated encephalopathy
• Myelopathy
• HIV-associated stroke
• HIV-associated neuropathy
• HIV-associated myopathy
HIV infection of the nervous system

4. Acute retroviral syndrome
• Acute HIV infection results in an acute retroviral
syndrome in the majority of those exposed
• aseptic meningitis 25%, facial nerve palsies,
radiculopathy, and acute demyelinating
polyneuropathy
• 2 to 6 weeks after infection

5. HIV-associated encephalopathy
• HIV-associated encephalopathy (HAE) or HIV-
associated dementia
• Adult
– gradual decline in cognitive, motor slowing, behavioral
changes
– Neuroimaging : diffuse atrophy, Nonenhancing
periventricular white matter
– EEG : diffuse slowing
– Cerebrospinal fluid (CSF): lymphocytic pleocytosis
and protein elevation

6. HIV-associated encephalopathy
• Children
– Similar to adult
– Development delay, first sign
– behavior

7. Myelopathy
• characteristic lesion : vacuolar changes,
predominantly in the lateral and posterior
columns of the thoracic cord
• Clinical : spasticity, weakness, sensory ataxia,
urinary incontinence, and erectile dysfunction
• Diagnostic by clinical,late manifestation of AIDS
• Insidious onset

8. Myelopathy
• MRI : atrophic changes of the thoracic cord with
occasional increased signal on T2-weighted and
fluid-attenuated inversion recovery (FLAIR)
sequences
• CSF : normal or mild a mild lymphocytic
pleocytosis and protein elevation
• Ddx : retroviruses (human T-cell lymphotropic
virus types I and II), cytomegalovirus (CMV),
herpes simplex virus type 2, and herpes
zoster, lymphoma, myeloma

9. HIV-associated stroke
• HIV infection is associated with an increased
risk for stroke
• antiphospholipid antibodies, protein S deficiency
• Vasculitis
• stroke must be considered in the differential
diagnosis of any HIV-positive individual with an
abrupt onset of neurological symptoms.

10. HIV-associated neuropathy
• Most common : Peripheral neuropathy
• acute inflammatory polyradiculopathy
• A painful distal symmetrical polyneuropathy
• Patients complain of numbness and burning of
the feet, which are exquisitely sensitive to touch,
hand symptom is usually late complication
• Electrical : nerve conduction velocity or
amplitude

11. HIV-associated myopathy
• Common : Symmetrical and proximal
myopathy
• Hip flexor , neck muscle
• Serum creatinine kinase elevated
• EMG : myopathic change
• Muscle biopsy : degeneration of myofiber

13. AIDS-related malignancies
• Kaposi’s sarcoma, Hodgkin’s lymphoma, non-
Hodgkin’s lymphoma (NHL), squamous cell
carcinoma, plasmacytoma, and
leiomyosarcoma
• Direct involvement of the CNS by these tumors
is rare, with one exception: primary central
nervous system lymphoma (PCNSL)
• high frequency in HIV-positive patients,
especially with the advent of HAART and
the prolongation of life associated with its use

14. Primary Central Nervous System
Lymphoma
• PCNSL is a rare NHL that accounts for less than
5% of primary CNS tumors.
• Clinical manifestations :
– highly variable and depend on the CNS site or sites
involved
– The tumor is often but not always multifocal and
occupies white matter spaces preferentially

15. Primary Central Nervous System
Lymphoma
• Symptoms range from nonspecific (i.e.,
nonlocalizing headache, mild encephalopathy,
delirium) to those associated with discrete
lesions in so-called eloquent areas of the
brain
• Radiology finding
– homogeneous contrast enhanced lesions with either
a hypodense appearance (on CT) or low signal
intensity (on T1-weighted MRI)
– Periventricular region
– Multiple but < , location : subependymal

16. Primary Central Nervous System
Lymphoma

17. Primary Central Nervous System
Lymphoma
• The entire neuraxis (eyes, brain, spinal cord,
and CSF spaces) must be evaluated for the
presence of PCNSL if suspected
– Eyes : slit-lamp examination to rule out vitreous tumor
– CSF : cytopathologic examination
– Avoiding to brain biopsy
– Wright stain,Papanicolaou stain
– Flow cytometry : predominant lymphocyte

18. Primary Central Nervous System
Lymphoma
• NeuroSx : call on biopsy suspected PCNSL
• Ddx : toxoplamosis, cerebral tuberculous
• Toxoplasmosis show signs of clinical
improvement within 3 days of treatment, and
improvement on neuroimaging follows within 7
to 10 days.
• In the case of suspected tuberculosis,
improvement occurs less rapidly

19. Primary Central Nervous System
Lymphoma
• Therefore, if this approach is adopted,
careful clinical assessment must be maintained,
and biopsy should be performed in any person
with early deterioration after the initiation of
empirical treatment of presumed infectious
disease.
• Survival after WBRT alone in PCNSL
patients is approximately 15 months and
decreases to 2 to 5 months in AIDS patients
• Methotrexate-based chemotherapy regimens

20. Infection
• Toxoplasmosis
• Cryptococcus
• Aspergillus
• Mycobacterium
• Treponema pallidum
• Bartonella
• JC virus
• Cytomegalovirus

21. Toxoplasmosis
• Toxoplasma gondii, Most common
• Exposure to cat,endemic area
• Clinical : encephalitis without meningeal
involvement
• CT,MRI : multiple nodular or ring enhancing
lesions c surrounding edema, hyperintense on
T2 , hyperintense on DWI
• Location : gray-white interface, basal ganglia,
thalamus

22. Toxoplasmosis
• Ddx of ring-enhancing lesions
– Lymphoma : homogenous pattern of
enhancement, DWI : uniformly restrict pattern,
periventricular and callosal involvement
– Other infection : tuberculosis and
cryptococcosis
– Small parenchymal hemorrhage in
toxoplasmosis

23. Toxoplasmosis
• Serum or CSF PCR for toxoplasma organism
• Empirical ATB : pyrimethamine and sulfadiazine
• Radiographic improvement within 2-4 wks
• Fail diagnosis or fail medical treatment : biopsy,
sent for Toxoplasma-specific DNA by PCR
• Reactivation form bradyzoite infection  repeat
biopsy

24. Cryptoccosis
• Cryptococcous neoformans
• Bird excrement,infected human via inhalation
• CD4 < 200 cell/ul
• Clinical : meningitis, Cranial neuropathies 
involve base of skull, hydrocephalus, stroke
• Radiographic : nonspecific, ring-
enhancement(ddx : toxoplasmosis), pseudocyst
in CSF space  dilated perivascular space

25. Cryptoccosis
• Blood C/S : positive for cryptococcosis
• CSF : india ink  budding yeast, cryptococcal
Ag, fungal culture
• Histopathologic : chronic granulomatous
changes with only a few organisms
• ATB : fluconazole or amphotericin B
• Relapse is high
• NeuroSx : place ventricular shunt for
hydrocephalus

26. Aspergillosis
• Aspergillus
• septate hyaline mold found in plants and soi
• severe sinopulmonary infections in
immunocompromised hosts(CD4 < 50 cell/uL)
• diffuse cerebritis, focal abscesses, or meningitis
• Vascular invasion  stroke
• Biopsy for definite diagnosis

27. Mycobacterial infection
• M. tuberculosis : CNS infection after pulmonary
infection
• M. avium and M. intracellulare : water, soil, and
animal host, CD4 < 50 cells/uL, MAC
• Clinical : meningitis, parenchymal brain lesion
are less common
• Radiology : leptomeningeal thickening,
tuberculoma may be single or multiple,gray-
white junction, supratentorial space

28. Mycobacterial infection
• MRI : isointense c low signal center on T2,target
lesion on contrast study
• Tubercular abscess : solitary, large,
multiloculated, enhance, mass effect, surround
by significant edema
• Purified protein derivative skin tests for M.
tuberculosis are unreliable in patients with HIV
• CSF culture : positive
• CSF AFB : negative

29. Mycobacterial infection
• AFB PCR : higher sensitivity but a negative PCR
result does not rule out M. tuberculosis in the
CNS
• CSF profile : elevated white blood cell count with
a lymphocytic predominance, glucose decrease
• NeuroSx : placement extraventruicilar drain in
tuberculous meningitis for obstructive
hydrocephalus

30. Mycobacterial infection
• M. tuberculosisbrain abscesses : drainage
• Treatment : multidrug regimen, duration varies
• Role of steroid is unknown

31. Treponema pallidum
• T.pallidum
• The tertiary stage of syphilis : diffuse systemic
involvement, including the CNS, Syphilitic
meningitis or meningovasculitis
• The classic manifestations of tertiary syphilis,
such as general paresis of the insane, tabes
dorsalis, and cerebral gummas, are less
common in the HIV/AIDS setting

32. Bartonella
• gram-negative bacteria Bartonella henselaeand
Bartonella Quintana
• cat-scratch disease and bacillary angiomatosis
• systemic disease with florid
meningoencephalitis is much more common
in AIDS patients
• suspected in those with typical skin lesion or
lymphadenopathy

33. JC virus
• JC virus
• CD4 < 100 cells/uL
• Spred via B lymphocyte to CNS  replicate in
oligodendrocytes  demyelination  focal
symptom  fatal
• Seizure

34. JC virus
• Laboratory finding:
– CSF : rarely pleocytosis, no decrease in glucose,
– CSF PCR : high specifity,but sensitivity vary
• MRI :
– T2/FLAIR : hyperintensity on white matter
– T1 : hypointensity
– pronounced posteriorly but can be found anywhere in
the brain, including the posterior fossa
– multifocal and have an asymmetric distribution

35. JC virus

36. JC virus
• Brain biopsy is important for diagnosis
• Histologic examination : demyelination
accompanied by “bizarre”-looking astrocytes
with pleomorphic nuclei
• No specific treatment
• HAART for immune reconstitutuion

37. Cytomegalovirus
• CMV
• CD 4 < 50 cells/uL
• myriad neurological syndromes
– Encephalitis : involvement periventricular tissue,
brainstem
– Myelitis
– Polyradiculopathy : most commonly affects the
lumbar spinal nerve roots, bilateral lower extremity
weakness and bowel and bladder symptoms
– Polyneuropathy : numbness and paresthesias

38. Cytomegalovirus
• Neurological examination : decrease in reflexes
consistent with a lower motor neuron syndrome
• MRI
– increased signal on T2/FLAIR images
– rare enhancement in the ependymal region the
periventricular white matter, and elsewhere in the
brain or brainstem
– Leptomeningeal enhancement

39. Cytomegalovirus
• Laboratory
– CSF : increased protein and glucose levels, as well as
white blood cells
– CS grow slowly
– CSF CMV PCR positivity is not sufficient by itself for
diagnosis because CSF CMV PCR may also be
positive in individuals with systemic CMV infection
in the absence of neurological syndrome

40. Cytomegalovirus
• Histology : eosinophilic intranuclear inclusions
with surrounding halos
• Specific treatment of CMV : ganciclovir or
foscarnet, or both
• HAART
• Mortality rate is high,within week

43. HIV treatment-related neurotoxicities
• peripheral neuropathy
– predominant neurological consequence of HAART
therapy
– The nucleoside analogue(dose dependent),
protease inhibitors
– Multifactorial : HIV infection itself, opportunistic
infection, and nutritional deficiencies.

44. HIV treatment-related neurotoxicities
• Immune reconstitution inflammatory syndrome
(IRIS)
– Restoration of immune competence as a result of
HAART can paradoxically cause clinical
deterioration because of innocent bystander–like
effects
– Risk for IRIS : initiating HARR, multiple infection
– neurological symptoms of IRIS : protean and largely
dependent on location.
– Onset occurs within 2 months of initiating HAART.

45. HIV treatment-related neurotoxicities
• Immune reconstitution inflammatory syndrome
(IRIS)
– Imagind study : contrast enhancement
– Histopatholgy : diffuse cytotoxic T-cell infiltrates
– NeuroSx : call for brain biopsy
– Management : problematic – discontinue, steroid

46. Thank you