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Clinical Care Options HIV - Capsule Summary

20/05/09 08:49 p.m.

Capsule Summary

Cytomegalovirus Encephalitis
Epidemiology
Autopsy reviews conducted before introduction of highly active antiretroviral therapy (HAART) documented ~30% of postmortem samples from HIV-infected patients had evidence of cytomegalovirus (CMV) encephalitis infection in the central nervous system (CNS) (Goplen et al, 2001) Clinically overt encephalitis is relatively rare clinical diagnosis in HIV-infected patients CMV infection at other sites (retina, adrenal glands, gastrointestinal tract, peripheral blood) often seen at time of presentation of neurologic symptoms CD4+ cell count typically < 50 cells/mm 3 (Saillour et, 1997) Short survival after onset of encephalitis symptoms (Brew, 2001) ~4 to 6 weeks ~2 years with aggressive therapy Decline of mortality with the introduction of HAART (Palella et al, 1998) Incidence and prevalence in HAART era assumed to be lower (Brew, 2001) Incidence of CMV retinitis and CMV disease have declined significantly since 1996 (Kaplan et al, 2000) Adult AIDS Clinical Trial Group (ACTG) Study 305, study of treatment of CMV encephalitis in HAART era, closed because of lack of accrual

Pathogenesis
Cytomegalovirus Reactivation of latent CMV infection (virtually all cases) Cell death in brain parenchyma, meninges, or periventricular region Dissemination of CMV to CNS

Clinical Presentation
Clinical picture not uniform nor characteristic for HIV-infected patients with CMV encephalitis Descriptions often inconsistent (ie, frequency of symptoms as cognitive disorders, altered consciousness, headache, and fever) However, can be rapidly progressive syndrome Most often includes fluctuating confusion

Common presenting symptoms Subacute dementia with periods of delirium, confusion, apathy Focal neurological deficits Cranial nerve deficits Headache

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Clinical Care Options HIV - Capsule Summary

20/05/09 08:49 p.m.

Less common symptoms Fever Incoordination Seizure

Diagnosis
Differential diagnosis Viral enecephalitis (eg, herpes simplex, varicella zoster) Meningitisviral, bacterial, TB, fungal Opportunistic infections of the CNS (eg, TB, toxoplasmosis) Any cause of raised intracranial pressure (eg, space occupying lesion, hydrocephalus) Lymphoma Progressive multifocal leukencephalopathy Toxic/metabolic causes Hydrocephalus

Neuroradiologic tests Computed tomography (CT) or magnetic resonance imaging (MRI) Diffuse areas of low attenuation in brain parenchyma (CT) or increased signal intensity in T2-weighted images (MRI) Ventriculomegaly may be present (not specific for CMV encephalitis) Periventricular enhancement in contrast study

Cerebrospinal fluid (CSF) analysis Essential for diagnosis CMV culture positive in < 50% Positive identification of CMV in CSF by CMV DNA detection by polymerase chain reaction (PCR) CSF may be normal or pleocytic May show elevated protein May show hypoglycorrhachia

Management
No controlled studies of therapy Anti-CMV therapy may be effective if given early Ganciclovir, foscarnet, cidofovir, as single agents or in combination

HAART Markedly reduced incidence of CMV encephalitis Improvement of immunodeficiency important Once patient stabilized, HAART should be initiated for improved immune function and better control of CMV infection

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Clinical Care Options HIV - Capsule Summary

20/05/09 08:49 p.m.

Key Reading
References Brew BJ. HIV Neurology. Contemporary Neurology Series, 61. New York, NY: Oxford University Press; 2001. Goplen AK, Liestol K, Dunlop O, Bruun JN, Maehlen J. Dementia in AIDS patients in Oslo; the role of HIV encephalitis and CMV encephalitis. Scand J Infect Dis. 2001;33:755-758. Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30:S4-S14. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-860. Saillour F, Bernard N, Ragnaud JM, et al. Incidence of cytomegalovirus disease in the Aquitaine cohort of HIV-infected patients: a retrospective survey, 1987-1993. Groupe d'Epidemilogie Clinique du SIDA en Aquitaine (GECSA). J Infect. 1997;35:155-161. Suggested Reviews Brew BJ. HIV Neurology. Contemporary Neurology Series, 61. New York, NY: Oxford University Press; 2001. Mamidi A, DeSimone JA, Pomerantz RJ. Central nervous system infections in individuals with HIV-1 infection. J Neurovirol. 2002;8:158-167. Price RW, Brew BJ. Central and peripheral nervous system complications. In: DeVita VT, Hellman S, Rosenberg SA (eds). AIDS: Etiology, Diagnosis, Treatment and Prevention. New York, NY: Lippincott-Raven Publishers, Inc; 1997:331-353. 2006 Clinical Care Options, LLC. May be copied for personal use only. To request permission for other use, contact 703-674-3510.

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