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.
A 57-year old immunocompromised Caucasian woman with a diagnosis of SLE in stable remission for the last nine years and treated with low dose prednisone was admitted to the Internal Medicine Ward because of a poor general condition lasting for seven days and weakness in the right leg without sensory deficit lasting for two days. During that time, she became disorientated and confused, while meningeal signs were negative. Laboratory tests showed a sedimentation rate of 26 mm/h, leucocytes 3.9 × 109/L with neutrophilia, erythrocytes 4.38 × 1012/L with thrombocytopenia of 125 × 109/L, mild liver lesion with aspartate aminotransferase (AST) 43 U/L, and alanine aminotransferase (ALT) 71 U/L. C3 and C4 complement components were normal, as well as immunoglobulins level (IgA 0.91 g/L, IgG 10.1 g/L, and IgM 1.67 g/L). Antiphospholipid antibodies were positive (aCL-IgM 69.1 MPL/mL, aCL-IgG 88.8 GPL/mL), ANA titar (IIF) was 1:1280, and dsDNA (ELISA) 52 IU/mL (normal < 30 IU/mL). An urgent brain MSCT was performed and showed discrete hypodense lesions of the left perinsular and hippocampal region. Due to the previous medical history, clinical presentation and initial imaging findings, central nervous system (CNS) lupus, and subacute ischemic cerebrovascular disease were suspected. Follow-up CT after 5 days showed a new lacunar hypodense lesion in the left cerebellar peduncle. Next, MR angiography was performed excluding signs of vascular anomalies, ischemia, and vasculitis. In the second week, the patient showed further deterioration of clinical symptoms with a decrease in the leucocyte count (L 2.7 × 109/L), normocytic anaemia (hemoglobin 109 g/L), and thrombocytopenia (platelets 92 × 109/L). C3 was 0.83 g/L and C4 was normal. Brain MRI in the second week of hospitalization revealed the full extent of brain impairment: multiple parenchymal supratentorial and brainstem demyelinating lesions on T2 and FLAIR sequences without postcontrast enhancement on T1WI ().\nSince we had an immunocompromised patient, CMV serology (ELISA) was also carried out with both IgM and IgG resulting in positive as well as blood CMV polymerase chain reaction (PCR) that revealed 4340 CMV copies per milliliter. A lumbar puncture was performed. Cerebrospinal fluid (CSF) analysis showed elevated protein at 1567 mg/L with normal glucose and lactate, 6 leucocytes/mm3, 645/mm3 erythrocytes, and negative bacterial culture. PCR detected CMV DNA in the CSF (<1000 copies/mL), while PCR for HSV and VZV were negative. There was no intrathecal oligoclonal bands synthesis. Clinical findings, course of the disease, laboratory tests (lower leucocytes, thrombocytopenia, hepatal lesion), neuroradiological features along with serology, and PCR tests suggested an ADEM associated with CMV reactivation. Antiviral therapy with gancyclovir and subsequently with peroral valganciclovir was administered for 29 days in total (until CMV PCR came negative in CSF and blood). High doses of intravenous methylprednisolone (125 mg intravenously for five days with consequent gradual dose reduction) and intravenous immunoglobulin (IVIG) 0.4 g/kg daily for three days were started simultaneously.\nThe patient‘s neurological status gradually improved. At the discharge, almost a month after admission, the patient was completely conscious with improved right leg paresis. Follow-up brain MRI, three weeks after the initial one, revealed partial regression of previously described demyelinating lesions. Further, a follow-up clinical examination 6 months after hospitalization showed mild right leg paresis and complete MRI regression of demyelinating lesions () Our patient had no similar recurrent attacks since.