Multiple encephalopathy syndrome: a case of a novel radiological subtype of acute encephalopathy in childhood.

INTRODUCTION: This report presents the case of a novel subtype of acute encephalopathy syndrome in childhood found in a patient with influenza type A infection; the patient exhibited evident magnetic resonance imaging (MRI) findings. CASE REPORT: A 4-year-old boy was transferred to our hospital for prolonged (lasting 60 min) status epilepticus with influenza encephalopathy. Mild brain hypothermia therapy was applied for 72 h, followed by targeted temperature management for 96 h with mechanical ventilation in the intensive care unit. Moreover, methylprednisolone pulse therapy and immunoglobulin therapy were administered. One month after the treatment, his physical status recovered such that he was able to run, take food orally, communicate verbally, and successfully return to kindergarten. Interestingly, serial MRI studies revealed findings that were compatible with 1) acute necrotizing encephalopathy (ANE), 2) mild encephalitis/encephalopathy with a reversible splenial lesion (MERS type II), 3) acute cerebellitis, and 4) acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) on days 2, 4, 7, and 16, respectively. CONCLUSIONS: To the best of our knowledge, these significant MRI findings associated with acute encephalopathy have never been reported. Thus, herein, we propose the new term radiological "multiple encephalopathy syndrome (MES)" based on our case of acute encephalopathy in childhood.

Specific HLA genotypes confer susceptibility to acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare and severe syndrome of acute encephalopathy triggered by viral infections. Cytokine storm is considered as the main pathogenetic mechanism of ANE. ANE is prevalent in East Asia, suggesting the association of host genetic factors. To elucidate the genetic background of Japanese ANE, we examined genotypes of human leukocyte antigen (HLA)-A, C, B, DRB1, DQB1 and DPB1 in 31 patients. Significant positive association was observed in both the allele frequency and positivity of DRB1*09:01 (P=0.043 and 0.025, respectively), as well as those of DQB1*03:03 (P=0.034 and 0.026, respectively). The carrier frequency of DRB1*09:01 and DQB1*03:03 alleles was higher in the patients (45.16%) than in controls (28.57%). These alleles are more common in East Asian than in European populations, and are reportedly associated with various autoimmune diseases in Japanese patients. Our data provide further evidence that altered immune response based on individual HLA genotypes may contribute to ANE pathogenesis.

Severe form of acute influenza encephalopathy with biphasic seizures and late reduced diffusion.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is clinically characterized by biphasic seizures on days 1, and 4 to 6; radiologically by no acute abnormality is visible during the first two days, while reduced diffusion in the subcortical white matter is seen during days 3 to 9, finally resulting in cerebral atrophy. We report here a Japanese child with clinically severe AESD associated with influenza A, whose sequential magnetic resonance imaging revealed cerebral swelling on day 1, reduced diffusion and central herniation on day 6, followed by cortical laminar necrosis and atrophy on day 30. The findings from this patient suggests that AESD has clinically and radiologically a wider spectrum than previously considered.

Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions.

OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions. MATERIALS AND METHODS: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16 x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

Detection of UV-induced K-ras codon 12 mutation by PCR and differential dot-blot hybridization in cells from Down syndrome and Cockayne syndrome.

By means of the polymerase chain reaction (PCR) and differential dot-blot hybridization, base substitution mutations of K-ras codon 12 were investigated in skin fibroblast cells from Down syndrome (DS) patients. Mutations were identified in DS cells after UV irradiation, predominantly in cells from younger patients. In contrast, no mutation was detected in cells from Cockayne syndrome (CS) patients who had the same features of premature aging as in DS but were not prone to cancer. This association of DS cells, but not CS cells, with inducibility of the K-ras codon 12 mutation may imply the proneness of DS patients to cancer development but a lack of proneness of CS patients.

Evaluation of magnetic resonance angiography with selective maximum intensity projection in patients with childhood moyamoya disease.

To determine whether magnetic resonance angiography with selective maximum intensity projection can facilitate the detection of cerebral moyamoya vessels in patients with childhood moyamoya disease, six patients with moyamoya disease (6 to 9 years old) and ten controls (4 to 16 years old) were evaluated by means of high resolution magnetic resonance angiography (matrix 512x384) with/without selective maximum intensity projection, and conventional angiography. In the patients with moyamoya disease, moderate or marked moyamoya vessels were detected but underestimated in 2/12 hemispheres on magnetic resonance angiography without selective maximum intensity projection. On magnetic resonance angiography with selective maximum intensity projection, moyamoya vessels were correctly assessed in 11/12 hemispheres (92%). In the controls, bilateral mild moyamoya vessels were detected in eight of 20 hemispheres (four of ten patients, under 7 years old), which were compatible with normal lenticulostriate arteries. Magnetic resonance angiography with selective maximum intensity projection is an accurate modality for assessing moyamoya vessels in moyamoya disease.