A 57-year old immunocompromised Caucasian woman with a diagnosis of SLE in stable remission for the last nine years and treated with low dose prednisone was admitted to the Internal Medicine Ward because of a poor general condition lasting for seven days and weakness in the right leg without sensory deficit lasting for two days. During that time, she became disorientated and confused, while meningeal signs were negative. Laboratory tests showed a sedimentation rate of 26 mm/h, leucocytes 3.9 × 109/L with neutrophilia, erythrocytes 4.38 × 1012/L with thrombocytopenia of 125 × 109/L, mild liver lesion with aspartate aminotransferase (AST) 43 U/L, and alanine aminotransferase (ALT) 71 U/L. C3 and C4 complement components were normal, as well as immunoglobulins level (IgA 0.91 g/L, IgG 10.1 g/L, and IgM 1.67 g/L). Antiphospholipid antibodies were positive (aCL-IgM 69.1 MPL/mL, aCL-IgG 88.8 GPL/mL), ANA titar (IIF) was 1:1280, and dsDNA (ELISA) 52 IU/mL (normal < 30 IU/mL). An urgent brain MSCT was performed and showed discrete hypodense lesions of the left perinsular and hippocampal region. Due to the previous medical history, clinical presentation and initial imaging findings, central nervous system (CNS) lupus, and subacute ischemic cerebrovascular disease were suspected. Follow-up CT after 5 days showed a new lacunar hypodense lesion in the left cerebellar peduncle. Next, MR angiography was performed excluding signs of vascular anomalies, ischemia, and vasculitis. In the second week, the patient showed further deterioration of clinical symptoms with a decrease in the leucocyte count (L 2.7 × 109/L), normocytic anaemia (hemoglobin 109 g/L), and thrombocytopenia (platelets 92 × 109/L). C3 was 0.83 g/L and C4 was normal. Brain MRI in the second week of hospitalization revealed the full extent of brain impairment: multiple parenchymal supratentorial and brainstem demyelinating lesions on T2 and FLAIR sequences without postcontrast enhancement on T1WI ().\nSince we had an immunocompromised patient, CMV serology (ELISA) was also carried out with both IgM and IgG resulting in positive as well as blood CMV polymerase chain reaction (PCR) that revealed 4340 CMV copies per milliliter. A lumbar puncture was performed. Cerebrospinal fluid (CSF) analysis showed elevated protein at 1567 mg/L with normal glucose and lactate, 6 leucocytes/mm3, 645/mm3 erythrocytes, and negative bacterial culture. PCR detected CMV DNA in the CSF (<1000 copies/mL), while PCR for HSV and VZV were negative. There was no intrathecal oligoclonal bands synthesis. Clinical findings, course of the disease, laboratory tests (lower leucocytes, thrombocytopenia, hepatal lesion), neuroradiological features along with serology, and PCR tests suggested an ADEM associated with CMV reactivation. Antiviral therapy with gancyclovir and subsequently with peroral valganciclovir was administered for 29 days in total (until CMV PCR came negative in CSF and blood). High doses of intravenous methylprednisolone (125 mg intravenously for five days with consequent gradual dose reduction) and intravenous immunoglobulin (IVIG) 0.4 g/kg daily for three days were started simultaneously.\nThe patient‘s neurological status gradually improved. At the discharge, almost a month after admission, the patient was completely conscious with improved right leg paresis. Follow-up brain MRI, three weeks after the initial one, revealed partial regression of previously described demyelinating lesions. Further, a follow-up clinical examination 6 months after hospitalization showed mild right leg paresis and complete MRI regression of demyelinating lesions () Our patient had no similar recurrent attacks since.
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. ).