A 38-year-old Japanese man was admitted to our hospital because of muscle weakness in his lower extremities. His and his family’s histories were unremarkable. Fifteen days before admission, he had a mild fever with fatigue. Simultaneously, itchy skin rashes emerge on his foot and face, particularly around his mouth. The patient was tentatively diagnosed as having hand, foot, and mouth disease. Prior to admission, his fever, fatigue, and skin rash began to resolve, but the lower limb weakness progressively worsened within a few days. On admission, his general condition was unremarkable. A neurological examination showed that he was alert and oriented. His higher cerebral functions and cranial nerves were intact. The patient showed spastic paraparesis, with weakness of both lower extremities at approximately 4/5 strength. Deep tendon reflexes were brisk in all extremities, with ankle clonus in both legs. Babinski sings were bilaterally positive. He had paresthesia below the level of the T7-8 dermatome. Difficulty in micturition was noted. The patient had no sign of meningeal irritation. The results of his laboratory tests showed that his complete blood cell count, chemistry, immunoglobulin levels, C-reactive protein, erythrocyte sedimentation rate, and urinalysis were all within reference values. In particular, alterations in the liver function test results, suggestive of infectious mononucleosis, were not observed. Serological tests for syphilis, hepatitis B and C, HIV, and human T-lymphotropic virus type 1 were negative. The test results were also negative for anti-nuclear antibodies, anti-double stranded DNA, and cytoplasmic and perinuclear types of antineutrophil cytoplasmic antibodies, antiphospholipid antibodies, and anti-aquaporin-4 antibody. Antibody titers were not elevated for herpes simplex virus immunoglobulin M (IgM), varicella zoster virus IgM, Epstein–Barr virus IgM, and CMV IgM. CMV IgG was found elevated significantly. Additionally, the tests for coxsackie A16 and enterovirus were not significantly elevated, although we could not perform a serodiagnosis with paired serum samples. A malignancy survey, in which contrast-enhanced CTs of the chest, abdomen, and pelvis were included, was conducted in the present patient, and no cancer was identified. Additionally, tumor markers (alpha-fetoprotein, CEA, CA19-9, and soluble interleukin-2 antigen) were all within normal ranges. Examination of CSF showed elevated white blood cells, although protein (34 mg/dl) and glucose (57 mg/dl) levels were within normal ranges. The CSF IgG index 0.8 was found to be mildly elevated. The myelin basic protein (40.0 pg/ml) levels were not increased, and there were no oligoclonal IgG bands in the CSF sample. Nerve conduction velocity studies of the peripheral nerves indicated that they were intact. Sensory evoked potentials obtained by tibial nerve stimulation demonstrated no reproducible waves. Both brain and spinal cord magnetic resonance images (MRI) obtained at admission appeared normal (Figs. , , and ). Brain and spinal cord MRI examinations with gadolinium-enhancement were also performed, although no significant enhancement was demonstrated. After admission, the patient’s weakness and deep sensation disturbance of the lower extremities progressively worsened. He was tentatively diagnosed with transverse myelitis, and treatment was started with intravenous methylprednisolone at a dose of 1000 mg/day for 3 days, followed by oral prednisolone (PSL) (60 mg/day). After 7 days, the muscle weakness in his lower extremities continued to worsen, and we added intravenous immunoglobulin therapy (IVIG) at a dose of 0.4 mg/kg for 5 days. Ten days after admission, intravenous administration of ganciclovir (600 mg/day, 19 days) was initiated because CMV DNA was found in his CSF following polymerase chain reaction analysis (PCR) performed at admission. The deterioration of his symptoms ceased, and the weakness in his lower extremities gradually recovered. Other findings in his CSF also improved, including the results for white blood cells (13/mm3; all cells were lymphocytes), protein (23 mg/dL), and glucose (62 mg/dL). The CSF samples were also negative for CMV. However, MRI performed again on day 26 after admission demonstrated a spinal cord lesion of high signal intensity at cervical levels C2–C6, suggesting that the spinal cord was involved and may have been responsible for the paraplegia, although his paraplegia continued to improve with treatment (Fig. ). Additionally, a hyperintense signal was observed in the right frontal subcortical white matter (Figs. and ). On day 40 after admission, the weakness and numbness of his lower extremities again worsened, and myoclonic movements appeared in his lower legs. Subsequently, a loss of finger dexterity appeared bilaterally. In addition, the patient developed dysarthria and truncal ataxia, the latter of which resulted in his inability to maintain a sitting position. Brain MR images demonstrated faint, irregular-shaped lesions involving cerebral white matter with dense T2-weighted and fluid attenuated inversion recovery (FLAIR) hyperintensities in the internal capsules, suggesting that extensive disseminated demyelination was actively ongoing (Figs. and ). The CSF examination results showed re-elevation of protein (39 mg/dL), and MBP (58.9 pg/mL) was also increased compared with results from the initial CSF study, although both levels were within normal ranges. The white blood cell count in the CSF did not increase (7/mm3). We considered the possibility that the patient had ADEM, and intravenous methylprednisolone (1000 mg/day, 3 days) was administered again, followed by IVIG (0.4 mg/kg, 5 days). After this treatment, his neurological deterioration ceased, but he had residual neurological sequelae. Time course of clinical symptoms, CSF results, treatment, and MRI findings in the present patient are schematically shown (Fig. ).
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.