Brainstem ClMV encephalitis in AIDS: Clinical case and MRI features

Article abstract-We describe the clinical case and MRI findings of a patient with acquired immune deficiency syndrome and pathologically confirmed cytomegalovirus encephalitis. Prevalent brainstem and cerebellar signs together with almost exclusive involvement as seen on MRI of posterior fossa structures at the onset of the symptoms were the main features of our case.
NEUROLOGY 1997;48:529-530

F. Pierelli, MD; G. Tilia, MD; A. Damiani, MD; P. Coiro, MD; M.C. Massara, MD; F. Bianco, MD; and I. Mezzaroma, MD

Patients with acquired immune deficiency syndrome (AIDS) often develop cytomegalovirus (CMV) infections of the nervous system such as, encephalitis, myelitis, and polyradiculopathy.' The diagnosis of CMV encephalitis (CMVE) is often difficult because of the absence of typical clinical, laboratory, and neuroimaging findings, and for its frequent association with other CNS disorders. We report the clinical case and MRI features of an AIDS patient with pathologically confirmed isolated CMVE clinically and radiologically presenting with brainstem and cerebellar involvement. Clinical case. A 27-year-old HIV-positive man, an intravenous drug user with no previous history of neurologic disease, developed interstitial pneumonia in December 1988. CD4 count was 75/mm3. He also complained of mild memory, attention, and concentration disturbances; neurologic examination showed mild unbalance of gait after eye closure and brisk deep tendon reflexes with slight left prevalence. Brain CT demonstrated diffuse cerebral atrophy, EEG was normal, and brainstem auditory evoked potentials (BAEP) from right ear stimulation showed an increased I-V interpeak latency. Cotr imoxazole and ceftriaxone were administered and pneuinonia remitted; neurologic signs also remitted in the following weeks. Two new episodes of interstitial pneumlonia occurred in the following months and were successfully treated with the same therapy; neurologic examination remained normal. At the beginning of May 1990, an acute balance impairment occurred; brain MRI showed small focal lesions in the left cerebellar hemisphere, right lateral medulla (figure), and right paraventricular white matter. On May 20, the patient was admitted to hospital: he had severe truncal and gait ataxia, dysmetria of all four limbs, nystagmus in all directions of gaze with diplopia, dysarthria, dysphagia, deep tendon hyperreflexia with left preponderance and bilateral Babinski sign. CD4 count was 50/mm3. Antitoxoplasma treatment was started and protracted for 15 days without any improvement. A lumbar puncture (June 10) showed a colorless CSF with 3 cells/mm3,30 mg/dl protein, and 50 mg/dl glucose; virologic and bacteriologic studies (anti-toxoplasma, anti-herpes simplex 1-2 GMV antibodies, p24 antigen, cryptococcus antigen search) were negative. Repeat MRI only showed an enlargement of the previously

described lesions in the posterior fossa. On June 19, the patient became somnolent and complained of intense headache; a high fever developed (39 "C); vomiting, yawning, and hiccoughs appeared and he died on June 28. Autopsy of the brain showed a widespread isolated CMV infection with prevalent involvement of posterior fossa structures.

Discussion. CMVE presenting with brainstem signs is uncommon in AIDS, and its clinical onset is nonspecific in most cases.2 Fuller et al.3 described
two patients who showed prominent brainstem signs and had combined HIV-CMV encephalitis. Three other patienW6 affected by brainstem encephalitis had pathologic signs of isolated CMVE, with prevalent brainstem lesions in two case^.^.^ In two series of 28 AIDS patients with pathologically proven CMV infection of the nervous system, four subjects presented with brainstem ~ i g n s .In ,a recent review of ~ ~ 14 AIDS patients with CMVE,* nonspecific signs of encephalopathy represented the main clinical feature of the infection; in two cases, cranial neuropathies resulting from direct CMV invasion of brainstem nuclei were also present. Cranial CT has shown posterior fossa lesions in two patients with CMVE6x9 and brain MRI in but the usual imaging pattern consists of periventricular inflammation that is not always related to the severity of pathologic changes.8 Our case represents a rare instance of CMVE with prevalent clinical and radiologic brainstem and cerebellar involvement. I n addition, clinical and electrophysiologic (altered BAEP) evidence of previous brainstem dysfunction appears interesting. Although BAEP alterations, sometimes subclinical, frequently occur in AIDS patients,1 pathologic studies suggest that the most common sites of CMV infection of the brain are the basal ganglia, diencephalon, and brainstem and that CMV may localize in the nervous system without significant clinical sequelae, because the virus is able to induce heterogeneous structural abnormalities associated with variable degrees of tissue resp0nse.l In this respect, an early CNS CMV localization in our patient cannot be excluded.
Copyright 0 1997 by the American Academy of Neurology
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Figure. Axial T,-weighted (TR 2620 msec, TE 50 msec) MRI shows small areas of increased signal intensity in the left cerebellar hemisphere (A) and right lateral medulla (BI.

In conclusion, in addition to neurotoxoplasmosis and primary cerebral lymphoma, CMVE should be considered in the differential diagnosis of brainstem encephalitis in AIDS patients. Polymerase chain reaction search for the CMV genome in CSF of AIDS patients with electrophysiologic or slight clinical signs of brainstem involvement is also suggested, as the virus seems to localize preferentially along the ventricular system and in brainstem structures.
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From the Institute of Nervous and Mental Diseases (Drs. Pierelli, Tilia, Damiani, Coiro, and Massara), Neuroradiology Unit (Dr. Bianco), and Institute of Allergology and Clinical Immunology (Dr. Mezzaroma), Department of Clinical Medicine, University La Sapienza. Rome, Italy. Received March 27, 1996. Accepted in final form June 24, 1996. Address correspondence and reprint requests to Prof. Francesco Pierelli, Istituto di Clinica delle Malattie Nervose e Mentali, Universita degli Studi di Roma La Sapienza, Viale delluniversita, 30, 00185 Roma, Italy.

References
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2. Wolf DG, Spector SA. Diagnosis of human cytomegalovirus central nervous system disease in AIDS patients by DNA amplification from cerebrospinal fluid. J Infect Dis 1992;166: 1412-1415. 3. Fuller GN, Guiloff RT, Scaravilli F, Harcourt-Webster JN. Combined HIV-CMV encephalitis presenting with brainstem signs. J Neurol Neurosurg Psychiatry 1989;52:975-979. 4. Masdeu JC, Small CB, Weiss L, et al. Multifocal cytomegalovirus encephalitis in AIDS. Ann Neurol 1988;23:97-99. 5. Behar R, Wiley C, McCutchan JA. Cytomegalovirus polyradiculoneuropathy in the acquired immunodeficiency syndrome. Neurology 1987;37:557-561. 6. Jakobson MA, Mills J, Rush J , et al. Failure of antiviral therapy for acquired immunodeficiency syndrome-related cytomegalovirus myelitis. Arch Neurol 1988;45:1090-1092. 7. Gozlan J, Salord JM, Roullet E, e t al. Rapid detection of cytomegalovirus DNA in cerebrospinal fluid of AIDS patients with neurologic disorders. J Infect Dis 1992;166:1416-1421. 8. Holland NR, Power C, Mathews VP, et al. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS). Neurology 1994;44507-514. 9. Laskin OL, Stahl-Bayliss CM, Morgello S. Concomitant herpes simplex virus type 1 and cytomegalovirus ventriculoencephalitis in acquired immunodeficiency syndrome. Arch Neural 1987;44:843-847. 10. Somma-Mauvais H, Regis H, Gastaut GL, et al. Potentials evoques multimodaux dans Iinfection par le virus de limmunodCficience humaine. Rev Neurol (Paris) 1990;146: 196-204.

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