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. ).
We present a clinical case of a 31-year-old man diagnosed with HIV-1 infection, with CD4 T cell count of 35 cells/mm3 (4%) and HIV RNA 305349 copies/mL (log10 5.48) having initiated ART with abacavir/lamivudine and nevirapine. Around two weeks after starting ART, the patient is admitted due to a sudden cognitive impairment (anhedonia and memory loss) with progression to gait change and imbalance. The cranial computerized tomography (CT) scan showed no lesions but the cranial MRI revealed ventriculoencephalitis ().\nThe cerebrospinal fluid (CSF) had 38 nucleated cells/mm3, 175 mg/dL proteins and 37 mg/dL glucose (glycaemia 82 mg/dL). The CSF CMV and EBV viral load were 189000 (log10 5.28) and 799 (log10 2.90) copies/mL with negative CSF neurotropic microorganism serologies and molecular identification (HSV 1/2, VZV, Cryptococcus, Brucella, Treponema pallidum, Borrelia burgdorferi, JC virus, Mycobacterium tuberculosis, and Toxoplasma gondii). The final considered diagnostic was mainly CMV-related ventriculoencephalitis and ganciclovir was started.\nNevertheless, the patient started left conjugate horizontal gaze palsy with abducting horizontal saccadic (or jerk-type) nystagmus of the right eye as well as a slight anisocoria with left eye miosis. These changes were enclosed in the one-and-a-half syndrome and left-sided Horner's syndrome. The patient also presented a grade II-III paresis of the right lower limb. The cranial CT scan (performed fifteen days later) revealed a dubious right linear protuberancial hypodensity without signs of intracranial hypertension.\nCranial MRI was repeated one month later revealing improvement of the ventriculitis signs but a larger hippocampus and left mesial temporal region involvement with a discrete increase of the lateral ventricles dimensions.\nDue to these clinical and imagiological changes and because we could not exclude tuberculosis infection, classic first-line tuberculostatic therapy was empirically started (stopped after excluding this infection) and foscarnet was added to ganciclovir (until a negative CMV viral load was achieved). At this point, the hypotheses of limbic encephalitis, epileptic activity or paraneoplastic encephalitis could not be excluded. The lumbar puncture was repeated and CSF antineuronal antibodies, HHV-8, and other neurotropic microorganisms were negative.\nThe electroencephalogram (EEG) showed frontal and frontotemporal bilateral activity with occasional periodic discharges, independent of nonabrupt three-phase bifrontal lesions. Anticonvulsant therapy with levetiracetam and topiramate was started. One month later, the cranial MRI was repeated and a new frontal lesion was detected. The body CT scan was normal. The imagiological reevaluation showed a slight improvement of the frontal lesion with new cerebellum lesions. The suspicion of lymphoproliferative disease was meaningful. Cranial MRI with diffusion and perfusion study with spectroscopy was performed and revealed very suggestive images of CNS lymphoma (). For definitive diagnosis, a stereotactic brain biopsy was done. The histological study revealed a polymorphic cellular infiltrate with histiocytes, CD3+ T-lymphocytes, and CD 20+ B-lymphocytes (mixture of numerous small cells and large activated cells with positive hybridization results for EBV-encoded RNA (EBER)). The histology was suggestive of polymorphic lymphoproliferative EBV-positive disease. The molecular studies were not done because the sample was insufficient to perform the clonality analysis (CSF EBV viral load was 12405 copies/mL; CSF HIV and CMV viral load were both undetectable).\nAt this point, chemotherapy with rituximab was started and radiotherapy was scheduled. Nevertheless, the patient developed a sudden neurological worsening with a generalized tonic-clonic seizure, refractory to the instituted measures, culminating in death.