HIV-associated CD8+ encephalitis

HIV-associated CD8⁺ encephalitis, or simply CD8⁺ encephalitis, is an inflammatory encephalopathy caused by perivascular and intraparenchymal CD8⁺ T cell infiltration, occurring in patients with human immunodeficiency virus (HIV) infection, despite often having adequate viral suppression. It is a distinct entity from both HIV-associated neurocognitive disorders and diffuse infiltrative lymphocytosis syndrome.

Epidemiology

HIV-associated CD8⁺ encephalitis is very rare, with less than 100 cases reported in the literature ^1,2. However, it is likely that it is under-recognized as a clinical entity ¹.

Associations

While multiple risk factors have been described, HIV-associated CD8⁺ encephalitis can also manifest in patients with well-controlled HIV without any risk factor ^1-3.

• Black ethnicity

  • it is worth noting that affected patients of this ethnicity have not been described from African nations

• intercurrent infection (not affecting the central nervous system)

• interruption of antiretroviral therapy

• history of antiretroviral therapy resistance

• immune reconstitution inflammatory syndrome (IRIS) after initial initiation of antiretroviral therapy

Clinical presentation

There is an acute or subacute presentation of encephalopathy, including ^1-3:

• headache (most common clinical feature)

• confusion and cognitive decline

• seizures

• focal neurological deficits

As the condition progresses, decreased consciousness can manifest, leading to coma and even death ^1-3.

In analysis of the cerebrospinal fluid (CSF), most patients demonstrate 'viral escape', with higher levels of HIV RNA present in the CSF compared to the serum ^1-3. Additionally, there is also a lymphocytic pleocytosis ¹.

Pathology

The exact pathophysiology is yet to be fully elucidated ^1-4.

Macrovascular appearance

Affected brains on autopsy are noted to be diffusely swollen ^1,3.

Microscopic appearance

There is perivascular and intraparenchymal infiltration by CD8⁺ T cells ^1,3,4. This is most florid in the white matter ^1,3,4. The presence of HIV is generally not demonstrable with immunohistochemistry ^1,3,4.

Radiographic features

MRI

MRI brain is always abnormal ¹. Characteristic findings include bilateral, diffuse, symmetric and confluent signal changes throughout the supra- and infratentorial white matter, with or without accompanying and extending similar changes throughout the deep grey matter ^1-6.

• T1: hypointense, often subtly so

• T2/FLAIR: hyperintense

• DWI: may have high signal (true diffusion restriction), particularly at the peripheries of T2/FLAIR abnormalities

• T1 C+ (Gd): may have enhancement, particularly punctate or linear enhancement in a perivascular distribution

Very rarely has a similar pathology been reported to occur in the spinal cord ⁷.

Treatment and prognosis

The mainstay of management is corticosteroids ^1-6. Some case reports also advocate for making alterations to the antiretroviral therapy regimen, such as being inclusive of agents with more central nervous system penetration ^1,3,5.

Differential diagnosis

• HIV-associated dementia ¹

  • often a more subacute-to-chronic clinical phenotype

  • MRI changes are typically periventricular and without contrast (gadolinium) enhancement

• acute disseminated encephalomyelitis ²

  • clinical presentation can be very similar, but often is more acute and may have an infective prodrome (or another trigger)

  • MRI changes usually not as symmetric or confluent

• lymphoma of the central nervous system ^1,2

  • clinical presentation can be very similar, although in the context of HIV often (but not exclusively) occurs in poorly controlled HIV

  • MRI changes often ependymal/subependymal and enhancement is usually more homogenous

• progressive multifocal leukoencephalopathy ^1,2

  • clinical presentation can be very similar, although in the context of HIV occurs in poorly controlled HIV

  • MRI changes usually asymmetric

• infective encephalitis

  • clinical presentation and radiological appearances can be highly varied depending on underlying infection

See also

• HIV-associated CD8⁺ transverse myelitis ⁷