Diagnosis Of Cytomegalovirus Encephalitis Research Articles

Extranodal involvement of posttransplant lymphoproliferative disorder detected on 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography

A 69-year-old man with a history of kidney transplantation presented with ring-enhancing lesions in the left frontal lobe, thalamus, and right insula (Figure 1a) on magnetic resonance imaging. He was hospitalized with a diagnosis of cytomegalovirus encephalitis and had taken anti-inflammatory therapy. Follow up imaging showed a decrease in lesion size in the left frontal lobe and thalamus; however, the right insular lesion increased in size and new ones were identified in the corpus callosum and periventricular white matter (Figure 1a). The tumor markers CA125, CYFRA21-1, CEA, PSA, and fPSA were all positive on blood testing. Because anti-inflammatory therapy was ineffective and malignant tumor could not be excluded on imaging alone, whole-body 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) was performed (Figure 1b). Body imaging showed multiple hypermetabolic nodular lesions in the thoracic and abdominal superficial soft tissue (maximum standardized uptake value, 13.06), which suggested malignancy. Head imaging showed decreased activity in the brain lesions. A diagnosis of lymphoma was suspected. Punch biopsy of a superficial soft tissue nodule was consistent with B cell-derived posttransplant lymphoproliferative disorder (PTLD) (Figure 1c,d). Brain MRI, 18F-FDG PET, and histopathological findings in a 69-year-old male patient with posttransplant lymphoproliferative disorder. (a) Abnormal signals in T2-flair MRI images within 3 months (solid arrow). (b) 18F-FDG PET/CT images show multiple lesions in superficial soft tissue nodules with hypermetabolism and decreased FDG activity of intracranial lesions (solid arrow). (c) Immunohistochemical staining shows positive CD3. (d) Immunohistochemical staining shows enlarged B cells (solid arrow). 18F-FDG, 18F-fluorodeoxyglucose; CT, computed tomography; PET, positron emission tomography. PTLD is a rare group of heterogeneous lymphoproliferative conditions that occur after solid organ or hematopoietic transplantation [1, 2]. With allograft transplantation, the anatomic site of PTLD involvement usually depends on the type of transplant [3]. Reported incidence rates of involvement of the central nervous system range between 10% and 15% [4, 5]. However, simultaneous involvement of the central nervous system [6] and superficial soft tissue [7] are rare. To date, only two cases of PTLD soft tissue nodules have been reported [4]. Characteristics of PTLD on magnetic resonance imaging are not specific; however, PTLD can be detected on 18F-FDG-PET with an overall sensitivity and specificity of approximately 90% [8, 9]. PTLD should be considered when multiple hypermetabolic superficial soft tissue nodules and central nervous system lesions are encountered in transplantation patients. Whole-body18F-FDG-PET/CT is more effective than single-site imaging for diagnosing or staging PTLD. Bojun Wang: Data curation (lead); Writing – original draft (lead). Tianbin Song: Conceptualization (equal); Writing – review & editing (equal). Chun Zhang: Conceptualization (equal); Supervision (equal). Jie Lu: Supervision (equal). Zhigang Liang: Supervision (equal); Writing – review & editing (equal). We thank Dr. Lianghong Teng (Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China) who provided support of pathological picture of this case. All the authors declare that they have no conflict or potential conflict of interest. This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from the patient and his parents for the anonymous use of his clinical, imaging, and histologic data for publication. The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Impairment of short‐term memory and Korsakoff syndrome are common in AIDS patients with cytomegalovirus encephalitis

The diagnosis of cytomegalovirus encephalitis (CMV-E) in AIDS patients is challenging as other illnesses may obscure the symptoms. Here, we characterize the clinical symptoms of CMV-E and link them to post-mortem findings. Patients and methods In 254 homosexual men with AIDS, followed from HIV diagnosis to death before the antiretroviral combination therapy era, CMV-E was suspected in 93 cases. All were CMV-positive in blood. Neurological examination, including cognitive testing was performed in 34 of them within 6 months before death. CMV-E was diagnosed by CMV-PCR in cerebrospinal fluid (n = 24) or by post-mortem (n = 24). The majority complained of forgetfulness (91%), balance difficulties (85%) and impotence (85%). Impaired short-term memory was present in 29 patients. It was extreme in 17, justifying the diagnosis of Korsakoff's syndrome. This was often associated with infectious CMV in blood (P = 0.01). Brainstem symptoms were found in 19 patients. Post-mortem examination often revealed ventriculoencephalitis. CMV was found primarily around the ventricles and in other structures, described in Korsakoff's syndrome. The location of CMV in the brain corresponded well to the clinical findings, demonstrating the close relationship between the neurological symptoms and the neuroanatomical lesions.

Diagnosis of cytomegalovirus encephalitis in patients with AIDS by quantitation of cytomegalovirus genomes in cells of cerebrospinal fluid.

A nested polymerase chain reaction (PCR) assay was used to determine the levels of cytomegalovirus (CMV) genomes in cells of CSF from 19 patients with AIDS and 12 human immunodeficiency virus type I (HIV-1) seronegative individuals with various neurologic disorders. Five AIDS patients had autopsy-proven CMV encephalitis (CMVE) and 14 patients had no evidence of CMV-related CNS manifestations. CSF cells from AIDS patients with confirmed CMVE harbored viral genomes at a median value of 3,333/10(5) cells (range, 1,667 to 5,333/10(5) cells; mean, 3,558/10(5) cells) compared with a median value of 125/10(5) cells (range, 9 to 1,000/10(5) cells; mean, 281/10(5) cells) for AIDS patients with CMV-unrelated symptoms and a median value of 1.9/10(5) cells (range, 0 to 562/10(5) cells; mean, 52/10(5) cells) for HIV-1 seronegative control subjects. A subset of CSF samples was assessed using a modified single round amplification PCR with a detection limit of 500 viral copies. CMV DNA was detected in all four specimens from AIDS patients with proven CMVE, in two of five AIDS patients without CMVE, and in none of five seronegative control subjects. Quantitation of CMV genomes in CSF cells is indicative of latent or productive CMV infection and is a reliable means for diagnosis of CMVE in patients with AIDS. Detection of a cutoff value of cellular CMV genomes by means of nonquantitative PCR may identify patients at risk for CMV infection of the CNS.

Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS.

A retrospective evaluation was conducted in patients with AIDS and an autopsy diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of clinical and laboratory findings in establishing a diagnosis. On autopsy of 100 patients, CMV encephalitis was diagnosed in 13 patients; eight had periventricular CMV encephalitis, four micronodular CMV encephalitis, and one both conditions. Seven patients had had a CMV infection previously (6 cases of retinitis, 1 case of colitis), and at the onset of encephalitis all of them were receiving a maintenance dose of ganciclovir. Examination of the CSF showed specific changes in patients with periventricular encephalitis. CT revealed no characteristic findings, while MRI showed an increased signal intensity on T2 weighted images. CMV DNA amplification by nested PCR was performed in nine patients with CMV encephalitis; PCR was positive in eight patients whose CSF was collected during CMV encephalitis, and negative in one patient whose CSF was collected six months before death. In conclusion, some clinical findings suggest a presumptive diagnosis, especially of periventricular encephalitis, and nested PCR appears to be a reliable and rapid technique for making an antemortem diagnosis.

The development of cytomegalovirus encephalitis in AIDS patients receiving ganciclovir

purpose: Cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency, syndrome (AIDS) requires lifelong therapy with either intravenous ganciclovir sodium or foscarnet sodium. From June 1989 through February 1992, seven patients with AIDS were diagnosed to have CMV retinitis, and all were treated with ganciclovir. Five of the seven developed abrupt preterminal mental status changes. All five with mental status changes received anti-CMV therapy until the time of death. Autopsies were performed in all cases to determine the cause of mental status changes. patients and methods: Five patients with AIDS and newly diagnosed CMV retinitis. Retrospective case analyses with autopsies. All five patients were treated with ganciclovir immediately upon the diagnosis of CMV retinitis and received ganciclovir at standard dosages until death. results: Four patients had clinically stable retinitis throughout the entire course of ganciclovir therapy. In the fifth patient, because of fundoscopic deterioration, foscarnet therapy was initiated 1-month prior to death. Cerebrospinal fluid analysis and magnetic resonance imaging, although abnormal, were not diagnostically specific. Neuropathologic examination revealed fulminant diffuse CMV encephalitis in all patients, with prominent ependymal and periventricular necrosis. conclusions: These results suggest that while ganciclovir therapy may clinically stabilize CMV retinitis in patients with AIDS, it does not appear to prevent the development of, or be effective in the treatment of, CMV encephalitis. Thus, clinicians should consider the diagnosis of CMV encephalitis in patients receiving ganciclovir who develop mental status changes and, if possible, alter therapy accordingly.