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 forty year old previously healthy Sri Lankan male presented with acute onset bilateral leg weakness which was progressive over two days following a brief febrile illness of three days. He did not give any history of trauma nor there was any history of tuberculosis. Initially he did not have urinary retention nor there was any sensory symptoms. He did not complain of shortness of breathing.\nOn examination he was found to have asymmetric flaccid paralysis of bilateral lower limbs with power grade one to two. Reflexes were diminished bilaterally and Babinski sign was equivocal. Examination of optic fundi and cranial nerves were normal. There was no demonstrable sensory level and joint position sense was initially preserved. Upper limbs were neurologically normal. Respiratory movements and sphincter function were preserved. Depending on initial findings a clinical diagnosis of Guillain-Barré syndrome was suspected and he was closely observed for the development of respiratory paralysis with monitoring of forced vital capacity and oxygen saturation.\nOn the fifth day of onset of symptoms his weakness worsened with additional flaccid paralysis of upper limbs and neck muscles. He was catheterized for acute retention of urine. Patient was urgently transferred to a high dependency unit but he did not develop respiratory paralysis necessitating ventilator support. Later he developed bilateral spastic paraparesis and positive Babinski sign with mild paraesthesia of lower limbs. But he did not develop a definite sensory level at anytime during the course of his illness.\nA nerve conduction study failed to show demyelination or axonal loss. Magnetic resonance imaging study of the spine showed hyperintensity of central portion of mid cervical cord from C 2 to C 5 level in T2 weighted and FLAIR images (Figure \n) There was mild swelling of cervical cord without significant change of signal intensity on T1 weighted image (Figure \n).\nBasic investigations were as follows; Na+ 139 mmol/l, K+-4.2 mmol/l, Serum creatinine-62 μmol/l, blood urea 8.7 mmol/l, White cell count 5000/mm3(N-76,L-18), platelet count 17500/mm3. Haemoglobin 9.3 g/dl, AST-51u/l, ALT-74u/l, Bilirubin 12 μmol/l, ESR-12 mm/hr, CRP-0.4 mg/dl, VDRL-negative, Fasting blood sugar 5.4 mmol/l.\nCerebrospinal fluid analysis done on the tenth day after onset of weakness was suggestive of a viral CNS infection with a protein content of 300 mg/l, glcose 4.3 mmol/l(RBS 10.9 mmol/l) and a leukocyte count of 350/mm3(92% lymphocytes). CSF infectious screen was positive for cytomegalovirus PCR(sensitivity more than 100copies/ml). This test was repeated and result was confirmed. Cytomegalovirus IgG and IgM were not detected in CSF. Polymerase chain reaction of CSF for herpes simplex virus(HSV) and Japanese encephalitis virus(JEV) were negative. Oligoclonal bands were not detected in CSF.\nConsidering the overall clinical picture, a working diagnosis of CMV associated transverse myelitis was made. Immunoglobulin levels and lymphocyte subset analysis failed to identify any immunodeficiency while HIV serology was negative.\nPatient received treatment with intravenous ganciclovir for a duration of 21 days starting on the 10th day of illness. He was also given maximal supportive care with physiotherapy and psychological support. A second CSF analysis done 22 days after the onset of symptoms revealed no cells and protein content of 390 mg/l. (CSF glucose 3.6 mmol/l RBS-6.5 mmol/l) Repeated CMV serology in blood, CSF and CSF PCR for CMV were negative on the 22nd day of illness.\nOne month after the onset of symptoms the upper limb power was improved (grade 5) but the lower limb power remained grade 3. He was transferred to a long term rehabilitation facility.