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 29 years-old man was admitted to our neurological department with five months of progressive disability in walking, paresthesia in the arms when bending the neck, numbness in the hands, and back pain. He had been treated for many years with aerosol salbutamol during exacerbations of asthma. Apart from periodic jaw spasms during the last five years, there were no apparent previous illnesses and no suspicion of infection within the last six months. During the last two years, he had been successfully treated for his injectable drug abuse with daily oral methadone. The patient had had negative hepatitis C virus RNA (HCV) serology two years before presentation. The neurological examination revealed positive Lhermitte`s sign, hypoesthesia in the hands, normal muscle strength in the upper limbs, reduced muscle strength in the legs (4 on a MRC scale), and reduced dorsiflexion of the feet (4 on a MRC scale). In addition, the patient had severe increased spasticity in the extensor muscles of the lower limbs, bilateral-positive Babinski, and a broad-based gait requiring support.\nSpinal cord MRI demonstrated extensive longitudinal spinal cord lesions from the cervical vertebral segment C1 to C5 and thoracic vertebral segment T2 to T11 (Figure ). The cervical lesion was located in the dorsal part and over a short distance in the lateral part on the right side on T2-weighted images. Discrete enhancement was found in the posterior part. Changes in the thoracic part were seen almost over the cord's entire cross section on the T2-weighted images, but enhancement was only demonstrated in the lateral part on both sides. The brain MRI was normal.\nA lumbar puncture was performed with cerebrospinal fluid showing slight pleocytosis with 11 mononuclear cells, a slightly increased protein to 0.64 g/l, normal IgG index and no oligoclonal bands, no antibodies against the varicella-zoster virus, herpes virus, entero-virus, or borrelia. The blood tests showed normal B12 vitamin, rheumatoid factor IgM and ANA, negative HIV serology, negative syphilis RPR, negative TB gamma interferon release assay, negative MOG- and AQP-4 antibodies, and increased ALAT to 200 U/l. Tests for HCV serology and HCV RNA were both positive.\nTreatment of HCV infection with Zepatier (elbasvir 50 mg and grazoprevir 100 mg) one tablet daily was initiated and continued for three months. Follow-up blood tests showed normalization of ALAT, negative HCV serology, and normalization of the spinal cord changes on MRI. The neurological findings were unchanged. There was no clinical suspicion of rheumatic, vascular or skin diseases and normal thyroid, white blood cells and renal function tests. With that condition, we found no indication for steroid treatment also taking into account previous episodes of psychosis in relation to his drug abuse.\nDespite a four-week course of inpatient rehabilitation, the physical condition was only slightly improved. Currently (two years later), walking distance is reduced, a stick is required when walking outside, and medication is still necessary for spasticity and neuropathic pain in the legs.