Acquired immune deficiency syndrome (AIDS)

General

Caused by a retrovirus that contains RNA.

Requires reverse transcriptase to convert its RNA to DNA and allow replication.

Numbers

Viral latency is 8 years, and once AIDS ensues,

50% die in <1 year
Most die in <3 years if untreated.

Types

HTLV-1 (human T cell lymphotropic virus)

Causes a chronic myelopathy with spastic paresis, but no sensory deficit and involves the anterior and lateral columns.
Occurs mainly in the Tropics (tropical spastic paraparesis) and Japan.

HTLV-2

Associated with chronic T cell Leukemia and lymphoma

HIV (HTLV-3)

A lentivirus with a surface molecule that interacts with T4.

Associated

Pneumocystis infections

Kaposi sarcoma.

Symptoms

CD4<200

Neurological involvement

50% of cases develop neurologic symptoms

80% have CNS abnormalities.

CNS complications at various stages include

Stages	Complications
Seroconversion	Aseptic meningitis, acute encephalitis, and myelopathy
HIV-positive	Asymptomatic or AIDS-related complex with aseptic meningitis
AIDS	Aseptic meningitis, AIDS dementia complex, lymphoma, and vacuolar myelopathy

CD4 Count	Organisms infections	Clinical clues
>500	Community acquired organisms	More likely to acquire bacterial pneumonia, HSV, zoster reactivation
200–500	Tuberculosis	Hemoptysis, night sweats, weight loss
<200	Pneumocystis jirovecii (carinii)	Hypoxia with activity, interstitial infiltrates, ↑ LDH Pneumonia (PCP)
ㅤ	Cryptosporidium	Profuse watery diarrhea
ㅤ	Candida	Oral thrush, oral lesions
ㅤ	Fungal pneumonia	Cavitary or diffuse infiltrates on X-ray
<100	Toxoplasma encephalitis (toxoplasmosis)	Ring enhancing lesions on CT brain
ㅤ	Candidal, HSV, or CMV esophagitis	Odynophagia, dysphagia
<50	Cytomegalovirus	Visual changes, esophagitis, enteritis, encephalitis
ㅤ	Cryptococcus (meningitis)	Headache, altered mentation, +India ink
ㅤ	Mycobacterium avium complex	Night sweats, weight loss, diarrhea, malaise
ㅤ	Primary CNS lymphoma (EBV assoc.)	Focal neuro deficits, seizures, confusion, weight loss

Infection with the HIV itself can cause direct neurologic involvement including

AIDS encephalopathy

The most common neurologic involvement,

Occurs in ≈ 66% of patients with AIDS involving the CNS

AIDS dementia complex

AKA HIV dementia complex

The most frequent AIDS disorder seen in 50% of patients.

It is believed to be caused by encephalitis or the viral impact on the neurons.

It consists of a triad of

Cognitive dysfunction (subcortical dementia),
Behavioral changes (psychoses and hallucinations),
Motor deficits (by centrum semiovale and brainstem involvement).

Aseptic meningitis

HIV encephalitis

Pathologic examination demonstrates microglial nodules in the white matter and subcortical gray matter with focal demyelination, neuronal loss, reactive astrocytosis, and calcifications in the parenchymal blood vessels and basal ganglia.

There are characteristic multinucleated giant cells that are unique to HIV in the CNS and are of macrophage origin.

Vacuolar myelopathy

Mainly involves the posterior and lateral columns of the low thoracic levels.

Pathologic examination demonstrates vacuolar changes with lipid-laden macrophages.

50% of AIDS autopsies,

But less often clinically.

Neuropathies

Cranial neuropathy

Bell's palsy

Peripheral neuropathy

Seen in 5–38% of AIDS cases
Caused by

Didanosine: medication used to treat HIV/AIDS
Demyelination
Arteritis

AIDS related Myopathy

Seen in 20% of AIDS cases, is characterized by inflammation, atrophy, polymyositis, and azathioprine-induced mitochondrial changes

Congenital lesions

Atrophy

Hydrocephalus ex vacuo

Microcephaly

Facial dysmorphism

Basal ganglia calcifications

Toxoplasmosis

CMV

See herpatic encephalitis

Seen in 30% of AIDS autopsies,

But only 10% are symptomatic with necrotizing encephalomyelitis.

Pathologic examination demonstrates microglial nodules, mainly in the gray matter and rarely in the white matter (unlike HIV).

There are Cowdry type A intranuclear and intracytoplasmic inclusions in the neurons and astrocytes.

Progressive multifocal leukoencephalopathy (PML)

Is caused by

Papovavirus family that includes

The papillomavirus (associated with warts and cervical carcinoma),
The polyoma BK virus (associated with haemorrhagic cystitis),
The JC and SV40 viruses (associated with PML)

Ubiquitous polyomavirus (a subgroup of papova virus, small nonenveloped viruses with a closed circular double DNA-stranded genome) called “JC virus”

(JCV, named after the initials of the patient in whom it was first discovered, not to be confused with Jakob-Creutzfeldt—a prion disease —nor with Jamestown Canyon virus, also confusingly called JC virus, a single stranded RNA virus that occasionally causes encephalitis in humans).
60–80% of adults have antibodies to JCV

The JC virus normally resides in the kidney.

Frequently manifests in patients with suppressed immune systems, including

AIDS: currently the most common underlying disease associated with PML

PML occurs in immunocompromised people and is found in 2% of AIDS autopsies.

Prior to AIDS, the most common associated diseases were chronic lymphocytic leukaemia & lymphoma
Allograft recipients: due to immunosuppression44
Chronic steroid therapy
PML also occurs with other malignancies, and with autoimmune disorders (e.g. SLE)

Pathologic findings

JC virus infection oligodendrogliocytes → focal demyelination (demyelination, ∴ affects white matter) with sparing of axon cylinders,

Surrounded by enlarged astrocytes and bizarre oligodendroglial cells with eosinophilic intranuclear inclusion bodies.

EM can detect the virus.

CSF is normal

Sometimes occurs in brainstem and cerebellum

It is bilateral, asymmetric, subcortical, spares the cortex, and usually starts in the posterior centrum semiovale.

There is minimal cellular infiltration, central destruction of oligodendrocytes, demyelination, and peripheral swollen irregular oligodendrocytes with ground-glass nuclei and intranuclear inclusions of “stick-and-ball” viral particles.

A close-up of a brain AI-generated content may be incorrect.

Clinical findings

Mental status changes
Blindness
Aphasia
Progressive cranial nerve, motor, or sensory deficits and ultimately coma
Seizures are rare

Imaging findings

Note: the appearance of PML may differ in AIDS patients from its appearance in non-AIDS patients.
CT

Diffuse areas of low density.

High intensity on T2WI

Normally involves only white matter (spares cortex);

However, in AIDS patients Gray matter involvement has been reported

No enhancement (on either CT or MRI),

Unlike most toxoplasmosis lesions

No mass effect
No oedema
Lesions may be solitary on 36% of CTs and on 13% of MRIs
Borders are usually more ill-defined than in toxoplasmosis

Clinical course

Usually rapidly progressive to death within a few months, occasionally longer survival occurs inexplicably
There is no effective treatment.
Some promise initially with anti-retroviral therapy

Definitive diagnosis requires brain biopsy

Sensitivity: 40–96%
Although it is infrequently employed.

JCV has been isolated from brain and urine.

Polymerase chain reaction (PCR) of JCV DNA from CSF has been reported, and is specific but not sensitive for PML

Primary CNS lymphoma

Seen in 5% of autopsies.

Occurs in ≈ 10% of patients with AIDS.

Invariably of B cell origin with large or mixed large/small cell types.

They are usually periventricular with perivascular spread.

Epstein–Barr virus (EBV) is frequently detected in the cells and may play a role in the development of the lymphoma.

Cryptococcus

In the normal population it causes meningitis, whereas in immunocompromised patients it causes encephalitis and cryptococcomas in the basal ganglia and midbrain

AIDS symptomatic infections

HIV encephalitis (60%)

Toxoplasma (30%)

Cryptococcus (5%)

PML (4%),

Less frequently lymphoma (not an infection), TB, syphilis, varicella-zoster, and CMV

Neurosyphilis

AIDS patients can develop neurosyphilis in as little as 4 mos from infection

Unlike the 15–20 yrs usually required in non-immunocompromised patients

Neurosyphilis can develop in spite of what would otherwise be adequate treatment for early syphilis with benzathine PCN

CDC recommendations: treat patients having symptomatic or asymptomatic neurosyphilis with

Penicillin G 3–4-million units IV q 4 hrs (total of 24-million units/d) for 10–14 days or
Penicillin G procaine 2.4 million units IM daily + probenecid 500mg QID orally, both for 10–14 days
Alternative: Rocephin 2 g IV once daily for 10–14 days for patients with a mild beta-lactam allergy
For severe beta-lactam allergy: PCN desensitization

CNS complications of AIDS (n=320)

Complication	%
Viral syndromes	ㅤ
Subacute encephalitisᵃ	17
Atypical aseptic meningitis	6.5
Herpes simplex encephalitis	2.8
Progressive multifocal leukoencephalopathy (PML)	1.9ᵇ
Viral myelitis	0.93
Varicella zoster encephalitis	0.31
Non-viral infections	ㅤ
Toxoplasma gondii	>32
Cryptococcus neoformans	13
Candida albicans	1.9
Coccidiomycosis	0.31
Treponema pallidum (neurosyphilis)	0.62
Atypical Mycobacteria	1.9
Mycobacterium tuberculosis	0.31
Aspergillus fumigatus	0.31
Bacteria (E. coli)	0.31
Neoplasms	ㅤ
Primary CNS lymphoma	4.7
Systemic lymphoma with CNS involvement	3.8
Kaposi’s sarcoma (including brain mets)	0.93
Stroke	ㅤ
Infarct	1.6
Intracerebral hemorrhage	1.2
Miscellaneous/unknown	7.8

ᵃCMV encephalitis occasionally occurs.

ᵇMore recent estimate of the incidence of PML in AIDS: 4%.

Common CNS complications seen in AIDS patients

Toxoplasmosis

Primary CNS lymphoma

Progressive multifocal leukoencephalopathy

Frequency in HIV

50%

30%

Organism

Toxoplasmosis Gondii

EBV

JC virus

Diagnosis

CSF culture/IgG

Biopsy/CSF flow cytometry /viterectomy/EBV PCR

Biopsy

Course of HIV

Occurs late in HIV infection

Multiplicity

Usually >5 lesions

Multiple but <5 lesions

May be multiple

Enhancement

Ring; “eccentric target sign,”

Homogenous

None

Location

Basal ganglia and gray white junction

Subependymal

Usually limited to white matter

Mass effect

Mild-moderate

Mild

None-minimal

Misc.

Lesions surrounded by edema

May extend across corpus callosum

High signal on T2WI, Low on T1WI

A close-up of a brain scan AI-generated content may be incorrect.

T1+C

A brain scan with a white spot AI-generated content may be incorrect.

A mri of the brain AI-generated content may be incorrect.

FLAIR

Treatment

Pyrimethamine and sulfadiazine + leucovorin

MTX + Steroids + RTX

No proven effective treatment (initiating or optimizing antiretroviral therapy -HAART may help)

Note

Cryptococcus is more common than PML or lymphoma, but usually manifests as cryptococcal meningitis, and not as a ring-enhancing lesion

Prognosis

Patients with CNS toxo have a median survival of 446 days, which is similar to that with PML but longer than AIDS-related PCNSL.

CNS lymphoma in AIDS

Survive on average a shorter time than similarly treated CNS lymphoma in nonimmunosuppressed patients (3 months vs. 13.5 mos).
Median survival is < 1 month with no treatment.
CNS lymphoma in AIDS tends to occur late in the disease, and patients often die of unrelated causes (e.g. Pneumocystis carinii pneumonia).