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New, Deadly, but Rare Encephalitis Described in 14 French HIV Patients
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Clinicians working at three Paris hospitals reported what appears to be a new HIV-related neurologic disease, which they call lymphocyte T8 infiltrative encephalitis because cytotoxic CD8 cells apparently trigger it [1]. Five patients had a relapse after therapy and 5 died during a median 4 years of follow-up.
This retrospective analysis of patients seen from 1999 through 2008 identified the new encephalitis in 8 men and 6 women, including 7 African Americans, 2 Arabic people, and 5 Caucasians. Nine people were infected with HIV heterosexually, 4 during gay sex, and 1 via transfusion. Two people had HBV and 1 had HCV. Other comorbid conditions included lupus, diabetes, hypertension, renal disease, bullous pemphygoid, and diffuse infiltrative lymphocytosis syndrome in 1 person each.
The group had a median age of 41 years and had HIV infection for a median of 10 years (range 1 to 18). Eleven people (78%) had a CD4 nadir below 200. Median CD4 count stood at 493 (range 6 to 900) and median viral load at 117 copies (range less than 40 to 10,000). Ten people (71%) had AIDS and 12 (86%) were taking antiretrovirals for a median of 4 years. Median antiretroviral central nervous system penetration effectiveness (CPE) score at diagnosis was 1.6. Median CPE score of regimens modified to treat the condition was 2.5.
The condition presented acutely in 5 people, subacutely in 6, and as a chronic condition in 2. Acute or subacute symptoms included epilepsy in 6, headache in 5, coma in 4, dizziness in 4, confusion in 4, dementia in 4, mild memory disorders in 3, neurologic deficit in 3, and "mood troubles" in 1. Symptoms usually occurred during immune reconstitution (early in the course of therapy) or during treatment interruption. The clinicians ruled out the following possibilities in differential diagnosis: JC virus, cytomegalovirus, herpes simplex virus, varicella zoster virus, Epstein-Barr virus, HHV-6, enterovirus, syphilis, Lyme disease, cryptococcosis, toxoplasmosis, tuberculosis, lymphoma, and multiple sclerosis.
Magnetic resonance imaging showed leukopathy with perivascular hyperintense T2-weighted lesions, while CT scans demonstrated lymphocytosis, nearly exclusively with CD8 cells. Nine people had brain biopsy, which showed lesions marked by edema, astrocytic and microglial activation, and perivascular and intraparenchymatous CD8-cell infiltration.
Eight people began steroid therapy, 9 changed their antiretrovirals, and 3 received cyclophosphamide. Clinical symptoms improved quickly with steroids, which usually began during antiretroviral intensification. But 5 people (36%) suffered a relapse. Through a median of 4 years of follow-up, 5 people (36%) died, 2 because of encephalitis and 3 because of encephalitis complications. Only 4 people (30%) have recovered to date.
The investigators noted that most patients had stable CD4 counts but did not have complete viral suppression in plasma. HIV load in cerebrospinal fluid averaged 2236 copies (range 1100 to 36,242 copies). The researchers listed the following sensitive diagnostic criteria:
-- Acute or subacute diffuse severe encephalitis
-- CD8-cell meningitis
-- On imaging, diffuse leukoencephalopathy, areas with restricted diffusion, and perivascular contrast enhancement
The investigators believe they have described "a new type of encephalitis in HIV patients characterised by severe neurological symptoms and homogeneous radiological and histological findings." They suggested that predisposing factors may be antiretroviral interruption, blips, virologic escape, or immune reconstitution inflammatory syndrome. Although it appears that cytotoxic CD8 cells trigger the disease, the precise mechanism remains to be defined.
Reference
1. Lescure FX, Amiel C, Gray F, et al. Lymphocytes T8 infiltrative encephalitis: a new form of neurological complication in HIV infection. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract WEAB0303.
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