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 17-year-old female presented with a history of flu-like symptoms (low-grade fever and body aches). One week after the initial presentation, she experienced a rapidly progressive and symmetric weakness in all four extremities. There was no visual or sensory impairment. No abdominal, respiratory, or cardiovascular symptoms were reported. The past medical history was negative, and the patient had no previous surgery. There was no current medication or recent vaccination history. She was not sexually active, and there was no environmental or sickly contact exposure. Subsequently, the patient became lethargic and progressed to a coma. She did not have seizures. On admission, the neurologic examination showed no response to verbal and pain stimuli. There was no neck rigidity. Kernig's sign was negative. A Babinski's sign was noticed in both extremities, along with clonus. Hyperreflexia was elicited in all four limbs. There was a maculopapular rash all over the trunk and extremities.\nA list of differentials were considered, which included infective meningitis, subarachnoid hemorrhage, encephalitis, multiple sclerosis, neuromyelitis optica (NMO), central nervous system (CNS) vasculitis, brain tumor, acute intoxication, and metabolic/endocrinologic conditions. A complete blood count and basic metabolic panels were normal. Urine toxicologic screening was negative. Head computed tomography (CT) showed no abnormality, and cerebrospinal fluid (CSF) analysis was unremarkable. Herpes virus, human immunodeficiency virus (HIV), CMV, rubeola, measles, and hepatitis serology panels were pending. NMO-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG) antibodies were not done due to technical conditions.\nShe was put on acyclovir, ceftriaxone, and vancomycin to cover both bacterial meningitis and herpetic encephalitis. Subsequently, HIV and serologies for hepatitis, rubella, and measles were negative. Polymerase chain reaction (PCR) for herpes virus in the CSF was negative as well. However, serum IgG and immunoglobulin M (IgM) for CMV demonstrated high titles, confirming recent systemic infection. A lumbar puncture was repeated, and at this time, the CSF showed a severe hypercellularity of 426 white cells/μL (normal range: 0 - 5 cells/μL) with 65% lymphocytes and 62 mg/dL of protein (normal range: 15 - 60 mg/dL). A glucose level was 95 mg/dL (normal range: 50 - 80 mg/dL). CSF oligoclonal bands (OCB) were not detected. MRI of the brain demonstrated multifocal, poorly marginated, and extensive areas of hyperintense signal on fluid-attenuated inversion recovery (FLAIR) sequences in the white matter, asymmetrically distributed in both hemispheres, as well as in the brainstem and cerebellar peduncles, compatible with acute demyelination lesions (Figure ). Cervical and thoracic spine MRI scans did not demonstrate an altered signal.\nAt this point, acute disseminated encephalomyelitis (ADEM) was diagnosed, and pulse therapy with methylprednisolone (15 mg/kg/day) was initiated for five days. On the third day of treatment, the patient showed neurologic improvement with the recovery of consciousness. She was able to move all four limbs and muscle power became normal. She had progressive neurologic recovery and was discharged after seven days with no motor deficits and mild cognitive decline.