A 21-year-old woman presented to the emergency room at our hospital with a history of confusion, high fever, and headache. Six days before emergency consultation, she had fever in the 38°C range and had a loss of appetite. She had a history of mumps at the age of seven. Other than that, there was nothing remarkable about her medical or medication history. After admission on the same day, her level of consciousness worsened, and she could barely open her eyes when called, but she did not speak, did not get the instructions, and did not move her limbs (Glasgow Coma Scale; E3V1M1). In addition, tonic-clonic seizures that lasted for a few minutes began to occur. Her initial vital signs were as follows: heart rate, 128 beats/min; respiratory rate, 24 breaths/min; blood pressure, 130/81 mmHg; body temperature, 39.9°C; and oxygen saturation, 94% with room air. Neurological examination revealed no neck stiffness and no other gross focal neurological deficits. Results of laboratory investigations are shown in . Her white blood cell count and C-reactive protein concentration were 11530/µl (neutrophils, 47.0%; lymphocytes, 27.0%; monocytes, 3.0%; and atypical lymphocytes, 23.0%) and 3.34 mg/L, respectively. Also, many atypical lymphocytes were observed in the peripheral blood smear. Ferritin levels were mildly elevated in the serum (68 ng/ml). Liver dysfunction was observed with an elevated aspartate aminotransferase (AST) level (116 IU/L) and an elevated alanine aminotransferase (ALT) level (183 IU/L). Serum creatinine and electrolyte concentrations were normal. Serum levels of interleukin-6 (IL-6) were elevated to 10.3 pg/ml (normal range, <4.0 pg/ml). Both nasopharyngeal swab tests for SARS-CoV-2 RNA and influenza antigen (A and B) were negative results. Based on the presence of liver dysfunction by laboratory investigations at admission, abdominal computed tomography (CT) was performed. An abdominal contrast-enhanced CT revealed a splenohepatomegaly but no sign of neoplasia (Figures and ). Cerebrospinal fluid (CSF) analysis showed lymphocyte-dominant pleocytosis with 186 nuclear cells/mm3 (180 mononuclear cells/mm3 and 6 polymorphonuclear cells/mm3) and protein concentration (41 mg/dL) and glucose concentration (96 mg/dL, with a serum glucose concentration of 140 mg/dL). Fluid-attenuated inversion recovery (FLAIR) images of brain magnetic resonance imaging (MRI) showed high-intensity lesions at the left medial temporal lobe, bilateral caudate nucleus, and left lentiform nucleus (Figures and ). Based on the patient's clinical findings and the results of various laboratory and imaging tests, we diagnosed her with possible meningoencephalitis, including herpes simplex virus encephalitis. On the day of admission, the patient was started on meningoencephalitis treatment with acyclovir (10 mg/kg/IV q8h), ceftriaxone sodium (2 g IV q12h), and fosphenytoin sodium (IV q24h) as antiepileptic drugs and steroid pulse therapy with high doses of intravenous methylprednisolone (1,000 mg) for 3 days.\nOn the second day of admission, she became afebrile, was able to speak, and was shown to improve her disturbance of consciousness. Serial FLAIR images of brain MRI showed no abnormality and the improvement of previous MRI findings (Figures and ). In the results of laboratory investigations on admission, blood CMV pp65 antigenemia assay was found to be positive (17 pp65-positive cells per 5 × 105 cells) and herpes simplex virus (HSV) DNA was negative in the CSF. Thus, we suspected that encephalopathy was caused by CMV and started to administer ganciclovir (5 mg/kg/IV q12h) instead of acyclovir. As the possibility of CMV infection increased, she consulted an ophthalmologist. As fundus findings, white punctate exudate and petechiae were observed in the retina of the left eye, and a diagnosis of CMV retinitis and uveitis was made (Figures and ). However, symptoms such as decreased visual acuity and visual field impairment had not yet been developed. After that, her general condition recovered rapidly, and after two weeks, she was able to walk and talk normally. In other results of laboratory investigations on admission, blood CMV DNA was detected by polymerase chain reaction (PCR) (1.6 × 103 copies/ml), but CSF CMV DNA was negative (). The test for Epstein–Barr virus (EBV) DNA in blood was also positive. Anti-CMV IgM antibody levels were elevated (8.54 titers), as were anti-CMV IgG antibodies (15.5 titers) (enzyme-linked immunosorbent assay; positive titer >2.0), in the serum. The human immunodeficiency virus (HIV) antibody testing using rapid tests was negative, and HIV RNA was undetectable in the serum. The number of CD4+ cells was normal. Antinuclear antibody, anti-double-stranded DNA antibody, and hepatitis screening results were negative, and serum immunoglobulin levels (IgG, IgM, IgA, and IgE) were within normal limits. No other potential immunosuppressant factors were recognized in the patient in terms of clinical manifestation or laboratory findings. In addition, the IgM antibody levels of various viruses, including EBV, varicella-zoster virus, and mumps virus, were also elevated in serum. After two weeks of administration of ganciclovir, blood CMV pp65 antigenemia assay became negative and the administration of this drug was terminated. In addition, blood CMV DNA was also negative (). Two weeks after admission, a retest of CMV antibodies showed that IgM was still positive (7.49 titers), but IgG antibody titer was significantly higher (71.0 titers) than before (15.5 titers) (). Lower serum levels of IL-6 were observed (2.4 pg/ml). Considering the presence of CMV DNA and pp65 antigenemia along with IgM kinetics, CMV infection in the patient was suggestive of a primary infection. During the subsequent course, her liver function improved, and retinitis did not worsen. She recovered 20 days after admission and was able to leave our hospital without sequelae. After 4 months, follow-up laboratory investigations were performed, and blood CMV pp65 antigenemia was confirmed to be negative. The IgM antibody levels of all viruses, including CMV, EBV, varicella-zoster virus, and mumps virus, changed to negative or showed a significant decrease (). She is on outpatient follow-up and is doing well.\nRegarding the relative changes in the patient's IgM and IgG levels over time, CMV IgM four months after admission was observed to decrease to 2.99 titers. Conversely, CMV IgG levels four months after admission were 42.5 titers, which were not significantly different from the values (71.0 titers) two weeks after admission.
We present a clinical case of a 31-year-old man diagnosed with HIV-1 infection, with CD4 T cell count of 35 cells/mm3 (4%) and HIV RNA 305349 copies/mL (log10 5.48) having initiated ART with abacavir/lamivudine and nevirapine. Around two weeks after starting ART, the patient is admitted due to a sudden cognitive impairment (anhedonia and memory loss) with progression to gait change and imbalance. The cranial computerized tomography (CT) scan showed no lesions but the cranial MRI revealed ventriculoencephalitis ().\nThe cerebrospinal fluid (CSF) had 38 nucleated cells/mm3, 175 mg/dL proteins and 37 mg/dL glucose (glycaemia 82 mg/dL). The CSF CMV and EBV viral load were 189000 (log10 5.28) and 799 (log10 2.90) copies/mL with negative CSF neurotropic microorganism serologies and molecular identification (HSV 1/2, VZV, Cryptococcus, Brucella, Treponema pallidum, Borrelia burgdorferi, JC virus, Mycobacterium tuberculosis, and Toxoplasma gondii). The final considered diagnostic was mainly CMV-related ventriculoencephalitis and ganciclovir was started.\nNevertheless, the patient started left conjugate horizontal gaze palsy with abducting horizontal saccadic (or jerk-type) nystagmus of the right eye as well as a slight anisocoria with left eye miosis. These changes were enclosed in the one-and-a-half syndrome and left-sided Horner's syndrome. The patient also presented a grade II-III paresis of the right lower limb. The cranial CT scan (performed fifteen days later) revealed a dubious right linear protuberancial hypodensity without signs of intracranial hypertension.\nCranial MRI was repeated one month later revealing improvement of the ventriculitis signs but a larger hippocampus and left mesial temporal region involvement with a discrete increase of the lateral ventricles dimensions.\nDue to these clinical and imagiological changes and because we could not exclude tuberculosis infection, classic first-line tuberculostatic therapy was empirically started (stopped after excluding this infection) and foscarnet was added to ganciclovir (until a negative CMV viral load was achieved). At this point, the hypotheses of limbic encephalitis, epileptic activity or paraneoplastic encephalitis could not be excluded. The lumbar puncture was repeated and CSF antineuronal antibodies, HHV-8, and other neurotropic microorganisms were negative.\nThe electroencephalogram (EEG) showed frontal and frontotemporal bilateral activity with occasional periodic discharges, independent of nonabrupt three-phase bifrontal lesions. Anticonvulsant therapy with levetiracetam and topiramate was started. One month later, the cranial MRI was repeated and a new frontal lesion was detected. The body CT scan was normal. The imagiological reevaluation showed a slight improvement of the frontal lesion with new cerebellum lesions. The suspicion of lymphoproliferative disease was meaningful. Cranial MRI with diffusion and perfusion study with spectroscopy was performed and revealed very suggestive images of CNS lymphoma (). For definitive diagnosis, a stereotactic brain biopsy was done. The histological study revealed a polymorphic cellular infiltrate with histiocytes, CD3+ T-lymphocytes, and CD 20+ B-lymphocytes (mixture of numerous small cells and large activated cells with positive hybridization results for EBV-encoded RNA (EBER)). The histology was suggestive of polymorphic lymphoproliferative EBV-positive disease. The molecular studies were not done because the sample was insufficient to perform the clonality analysis (CSF EBV viral load was 12405 copies/mL; CSF HIV and CMV viral load were both undetectable).\nAt this point, chemotherapy with rituximab was started and radiotherapy was scheduled. Nevertheless, the patient developed a sudden neurological worsening with a generalized tonic-clonic seizure, refractory to the instituted measures, culminating in death.