Mitsuo Toyoshima

Early predictors of status epilepticus-associated mortality and morbidity in children

BACKGROUND Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk. OBJECTIVES To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children. METHODS We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes. RESULTS Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24 months); seizure duration >90 min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels (<61 or >250 mg/dL); serum aspartate aminotransferase (AST) ⩾56 U/L; and C-reactive protein (CRP) levels >2.00 mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant. CONCLUSIONS Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children.

Clinical and MRI characteristics of acute encephalopathy in congenital adrenal hyperplasia

Acute encephalopathy in childhood is frequently associated with common infections, especially in East Asia. Various types have been identified although many cases remain unclassified. Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease presenting impairment of cortisol biosynthesis. We report three CAH children with acute infection-related encephalopathy. They exhibited disturbed consciousness or seizures, which did not improve after glucocorticoid administration, accompanied by clinical and laboratory findings of adrenal insufficiency. Brain MRI disclosed various patterns of white matter lesions, suggesting different types of acute encephalopathy such as clinically mild encephalitis/encephalopathy with a reversible splenial lesion or hemiconvulsion-hemiplegia syndrome. Acute encephalopathy should be considered and brain MRI immediately performed when impairment of consciousness does not improve after intravenous glucocorticoid administration in CAH patients. Further research is required to elucidate the epidemiology and pathogenic mechanisms of acute encephalopathy in CAH.

Association of Acute Cerebellar Ataxia and Human Papilloma Virus Vaccination: A Case Report

INTRODUCTION We report the case of a patient who developed symptoms of acute cerebellar ataxia (ACA) after administration of the human papilloma virus (HPV)-16/18 vaccine. PATIENT AND METHOD This patient developed symptoms of ACA, including nausea, vertigo, severe limb and truncal ataxia, and bilateral spontaneous continuous horizontal nystagmus with irregular rhythm, 12 days after administration of the HPV-16/18 AS04-adjuvanted cervical cancer vaccine. After this, the patient received methylprednisolone pulse and intravenous immunoglobulin (IVIG) therapies as well as immunoadsorption plasmapheresis. RESULTS Severe ACA symptoms did not improve after methylprednisolone pulse and IVIG therapies, but the patient recovered completely after immunoadsorption plasmapheresis. CONCLUSION This temporal association strongly suggests that ACA was induced by the vaccination.

Proinflammatory cytokines in cerebrospinal fluid from patients with nontyphoidal Salmonella encephalopathy.

Nontyphoidal Salmonella (NTS) encephalopathy is characterized by rapidly progressive brain dysfunction that develops after NTS enteritis. The mechanism of central nervous system involvement remains unclear. We examined cerebrospinal fluids from 7 patients for cytokines and found elevated interleukin-6, interleukin-8, and monocyte chemotactic protein-1 concentrations in all the patients, suggesting that the proinflammatory cytokines are involved in the pathogenesis of NTS encephalopathy.

Myocerebrohepatopathy spectrum disorder due to POLG mutations: A clinicopathological report.

We report on the clinical, neuropathological, and genetic findings of a Japanese case with myocerebrohepatopathy spectrum (MCHS) disorder due to polymerase gamma (POLG) mutations. A girl manifested poor sucking and failure to thrive since 4 months of age and had frequent vomiting and developmental regression at 5 months of age. She showed significant hypotonia and hepatomegaly. Laboratory tests showed hepatocellular dysfunction and elevated protein and lactate levels in the cerebrospinal fluid. Her liver function and neurologic condition exacerbated, and she died at 8 months of age. At autopsy, fatty degeneration and fibrosis were observed in the liver. Neuropathological examination revealed white matter-predominant spongy changes with Alzheimer type II glia and loss of myelin. Enzyme activities of the respiratory chain complex I, III, and IV relative to citrate synthase in the muscle were normal in the biopsied muscle tissue, but they were reduced in the liver to 0%, 10%, and 14% of normal values, respectively. In the liver, the copy number of mitochondrial DNA compared to nuclear DNA was reduced to 3.3% of normal values as evaluated by quantitative polymerase chain reaction. Genetic analysis revealed compound heterozygous mutations for POLG (I1185T/A957V). This case represents the differential involvement of multiple organs and phenotype-specific distribution of brain lesions in mitochondrial DNA depletion disorders.

Immunoglobulin A deficiency following treatment with lamotrigine.

Lamotrigine (LTG) is an anti-epileptic drug and mood-stabilizing agent, whose adverse effects include skin rash and dizziness. Interactions with the immune system are rare, and only a few cases linking hypogammaglobulinemia to LTG treatment have been previously described. In this report, we describe a case in which a patient developed hypogammaglobulinemia, and a subsequent immunoglobulin A (IgA) deficiency, following LTG treatment. As a result of her immunodeficiency, the patient presented with a severe urinary tract infection and required intravenous immunoglobulin. Serum levels of immunoglobulin G and M had recovered by seven months and one month after the discontinuation of LTG, respectively; however, IgA levels remained low (less than 4mg/dL) two years post-treatment. While previous reports have demonstrated IgA deficiencies in patients prescribed other antiepileptic drugs, this is the first case of an IgA deficiency following LTG administration.

Quantitative computed tomography for enzyme replacement therapy in Pompe disease

OBJECTIVE Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme, acid alpha-glucosidase (GAA). To the best of our knowledge, no studies have reported the results of systematic and sequential CT analyses before and during ERT. In this study we have treated three patients with late onset Pompe disease by ERT, and investigated the efficacy of treatment by computed tomography number. METHODS We measured the serial changes in the computed tomography (CT) number of multiple organs in three patients with late onset of Pompe disease during 24 months of enzyme replacement therapy (ERT). RESULTS Before treatment, the liver and muscle CT numbers were higher in these patients than in the controls. The liver CT number decreased after performing ERT. Furthermore, the urinary glucose tetrasaccharide levels, a biomarker of glycogen accumulation, were elevated before ERT and reduced thereafter. CONCLUSIONS The findings in these cases suggest that the elevation of the liver CT number represents glycogen accumulation in the liver and that the analysis of the liver CT number is therefore a useful tool for assessing the efficacy of ERT.

Vertebral fusion in a patient with supernumerary‐der(22)t(11;22) syndrome

A patient with a 47,XX,+der(22)t(11;22)(q23.3;q11.2) karyotype exhibited brisk tendon reflex and Babinski sign with suggested pyramidal sign. A three‐dimensional computed tomographic reconstruction revealed a T1‐T2 vertebral fusion without hemivertebrae. Sagittal magnetic resonance imaging revealed degenerative disk changes, mild disk herniation, and mild spinal cord compression. Congenital vertebral fusion may be one of the anomalies in supernumerary‐der(22)t(11;22) syndrome. Once clinical diagnosis of this chromosome aberration is established, radiologic evaluation of vertebrae and spinal neuroimaging should be performed.