HIV-mediated CD8 encephalitis: An under recognised entity

Background: Combined antiretroviral therapy (cART) has been associated with significant decrease in the mortality and morbidity in patients with HIV/AIDS. However, there has been increased recognition of immune dysregulation syndromes related to recovery of immunity on cART. HIV-mediated CD8 encephalitis is a rare neurological syndrome due to perivascular inflammation caused by infiltration of CD8+ cells. Methods & Materials: We report the clinical and pathological features of three cases of CD8 encephalitis which will sensitise the clinicians to have high index of suspicion to recognize this entity early. Results: All three patients were men with a mean age of 42.3 years. The mean duration of HIV was 10 years. The patient’s mean CD4 at presentation was 392 cells/microL and blood HIV viral load was 11,588.3 copies/ml. All patients presented with an average duration of 4 months with cognitive decline, especially memory disturbances and tremors. The mean cerebrospinal fluid (CSF) cell count was 65 cells/ml, lymphocyte predominant (mean 97%), and protein was 171.3 mg/dl. The CSF lymphocyte subset analysis showed a median CD8 cell proportion of 54.7%. CSF was tested negative for viral infections (HSV1, HSV2, CMV, JC virus and VZV) and VDRL. The CSF cultures were sterile and GeneXpert was negative. MRI brain revealed diffuse hyper intensities involving the deep grey and white matter and typical perivascular hyperintensities were present in one patient. All patients were started on steroids after excluding other etiologies. Two patients made a complete recovery while one patient in whom the diagnosis was delayed succumbed to the illness. Postmortom brain biopsy of the patient who had a fatal outcome demonstrated perivascular cuffing with lymphocytes positive for CD8 and negative for CD4 and CD20 markers on immunohistochemistry, consistent with CD8 encephalitis. Conclusion: CD8 encephalitis is a rare but potentially treatable cause of cognitive decline in patients with HIV on cART. The typical presentation includes memory impairment with extrapyramidal symptoms like tremors with lymphocytosis in CSF and predominant CD8 cells in CSF. MRI may show the typical perivascular hyperintensities in the deep brain tissue. Aggressive early steroid treatment after excluding opportunistic infections is likely to result in complete recovery.