Early diagnosis and successful treatment of acute cytomegalovirus encephalitis in a renal transplant recipient

Abstract

We report the case of a 40-year-old male HIV-negative renal transplant patient with allograft rejection and immunosuppressive therapy who presented with acute cytomegalovirus (CMV) encephalitis. CT and MRI of the brain were normal but EEG showed diffuse slowing and dysrhythmia. In cerebrospinal fluid (CSF) initially 81 cells/microliters were found and immunocytochemistry showed a decreased CD4/CD8 ratio and increased values of activated lymphocytes, natural killer cells and immunoglobulin-containing cells. CMV-specific IgM antibodies in CSF and serum, immunostaining of CMV antigen in CSF cells and virus culture from CSF and urine were negative. During the first 3 weeks of illness no intrathecal production of immunoglobulins could be detected. Early diagnosis of CMV encephalitis was made by in situ hybridization (ISH) on CSF cell preparations and the polymerase chain reaction (PCR) which was positive in CSF and blood. On day 26 diagnosis was confirmed by detection of CMV-specific intrathecal IgG production. The patient was treated with ganciclovir, anti-CMV immunoglobulins and intrathecal beta interferon. He recovered completely after 2 months. Our data demonstrate the usefulness of ISH and PCR in the early diagnosis of CMV encephalitis and perhaps may encourage the use of intrathecal beta interferon in other patients with this disease.

Cytomegalovirus Infections of the Nervous System

“…By comparing CSF PCR find ings with histopathological findings or virus isolation from the CSF, its sensitivity, specificity, and positive and negative predictive values for the diagnosis of HCMV encephalitis have been found to be between 80 and 100% in the majority of studies [89][90][91][92], CSF PCR is sensitive and specific for the diagnosis of HCMV polvradiculomyelitis [93][94][95][96] and may also be of value in the diagnosis of HCMV-associated peripheral neuropathies [55], In a few instances, CSF PCR has also been successfully applied to the diagnosis of HCMV infections of the nervous system in both non-AIDS immunocompromised and in immuno competent patients, the diagnosis of HCMV encephalitis being confirmed by classical methods, i.e. virus isolation Cytomegalovirus Infections of the Nervous System from the CSF or the demonstration of an intrathecal anti body production [61,62], Besides allowing a rapid etio logical diagnosis, the use of CSF PCR has also led to the better characterization of the clinical syndromes associat ed with HCMV infections of the nervous system. Further more, the application of this technique has proved to be important in the recognition of atypical or newly recog nized forms in both AIDS and immunocompetent pa tients, thus extending the spectrum of the neurological manifestations associated with HCMV [62.…”

“…Pathological brain examinations in organ transplant recipients have revealed the presence of cytomegalic cells, either isolated or within microglial nodules, but without the periventricular or focal necrosis commonly observed in AIDS patients [58,59]. Clinically, both acute encepha litis and diffuse encephalopathy have been described, the latter being reported in patients with microglial nodule encephalitis at autopsy [60,61].…”

“…121], CSF HCMV-DNA titer may decrease following antiviral therapy, but clearance is infrequent [99], On the contrary, HCMV polyradiculitis responds to ganciclovir in approxi mately one half of the cases, although the response may be delayed for several weeks after the initiation of therapy [49,50]. Reports of small patient series suggest that ganci clovir may also be effective in the treatment of patients with mononeuritis multiplex and painful symmetrical po lyneuropathy [52,55], In both non-AIDS immunocom promised and immunocompetent patients, a favorable disease outcome following ganciclovir therapy has been reported in a few cases [61,62,122],…”

“…The detection of CSF and serum antibodies against HCMV may be useful in immunocompetent patients, to demonstrate a HCMV-specific intrathecal antibody syn thesis [62], This technique has also been applied in the diagnosis in immunocompromised patients, including AIDS patients [61,106]. However, because of their pro found immunosuppression, AIDS patients do not general ly develop a sustained intrathecal antibody response, and their CSF may contain low levels of nonspecific or poly specific intrathecal antibodies due to HIV-induced immunoactivation [107], Brain biopsies have rarely been successfully used in patients with HCMV encephalitis, since focal brain le sions revealed by neuroradiological procedures are infre quent [57], On the contrary, peripheral nerve biopsy is the currently used method for identifying HCMV peripheral neuropathy and defining its nature [53], The examination of nervous system tissue is mainly limited to the study of autopsy material.…”

Diagnostics of Persistent Viruses: Human Cytomegalovirus as an Example

“…Central nervous system involvement due to HCMV is found rarely in adult immunocompromized transplant recipients [57,58].…”