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 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.