Huei-Shyong Wang

Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County

We have done an epidemiological study in an elementary school with 2000 Taiwanese children aged from 6 to 12 years, and found 11 of them with Tourettes syndrome. The prevalence rate of Tourettes syndrome was around 0.56%. The ratio of male to female was 9 to 2. The comorbid rate of attention-deficit/hyperactivity disorder was 36%, self-injurious behaviors 27%, and obsessive-compulsive behaviors 18%. The familial rate of Tourettes syndrome was 27%. We also found that another 98 children had transient tic disorders. For 73% of patients with mild tics, understanding and acceptance from family, teachers, and friends are the most important things. When tics are so severe that medication is necessary, haloperidol is no longer the first or only choice. We tried clonidine, atypical neuroleptics such as risperidone or olanzapine, or pergolide. The first support group was established in 1999 for children with tics in Taiwan and transformed to Taiwan Tourette Family association in June 2001 to provide further service for Tourettes syndrome.

Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine

We present a female infant with seizures responsive to pyridoxal phosphate but that are resistant to pyridoxine. The mechanism by which pyridoxal phosphate controls seizures in this patient is unknown. Her seizures are perhaps not solely caused by pyridoxal phosphate deficiency. It is suggested that in addition to glutamic acid decarboxylase abnormality, the path from the absorption, transportation, phosphorylation, and oxidation of pyridoxine to pyridoxal phosphate in this patient might be defective. It should be considered whether pyridoxal phosphate can be the drug of choice instead of pyridoxine in treating patients suspected of pyridoxine-dependent epilepsy to reduce failure rate and further delay in seizure control.

Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis

Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.

High expression of stathmin protein predicts a fulminant course in medulloblastoma.

OBJECT Stathmin, an important cytosolic phosphoprotein, is involved in cell proliferation and motility. This study was performed to elucidate the role of stathmin in the progression of medulloblastoma. METHODS The expression of stathmin protein was examined by immunohistochemical staining of tumor sections obtained in 17 consecutive patients with medulloblastoma who underwent resection between 1995 and 2005. Four patients were excluded because they were either lost to follow-up or underwent biopsy sampling only, leaving a total of 13 patients in the study. The stathmin expression was scored according to the immunoreactive fraction of tumor cells, and the level was correlated with various clinicopathological factors. RESULTS The expression level of stathmin protein was < or = 10% in 9 patients, 11-50% in 1, and > 50% in 3. No staining was seen in the tissues adjacent to the tumors. For comparison, the authors grouped the expression level of stathmin into high (> 50%) and low (< or = 50%). It was found that patients with high expression of stathmin had more frequent tumor dissemination at the time of resection or soon after total excision of the tumor (p = 0.0035), and hence experienced a fulminant course with lower patient survival (p < 0.0001), with an average survival period of 6.7 months (range 2-10 months). The expression level of stathmin did not correlate with patient age, sex, CSF cytological findings, use of adjuvant therapies, Ki 67 index, or risk classification of the tumors according to previously described categories in the literature. CONCLUSIONS High stathmin expression correlates with tumor dissemination, is an important prognostic factor of medulloblastoma, and may serve as a useful marker for more intensive adjuvant therapies.

Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1

Objectives –  To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients.

Clinical Variants of Guillain-Barré Syndrome in Children

Guillain-Barré syndrome is characterized by acute progressive weakness, areflexia, and maximal motor disability that occur within 4 weeks of onset. Various clinical subtypes have been described since the original description of the syndrome. This study aimed to identify characteristics of clinical variants of Guillain-Barré syndrome through retrospective review of cases in Chang Gung Childrens Hospital from 2000-2010. Forty-three Guillain-Barré syndrome patients were evaluated based on clinical presentations and an electrodiagnostic study. The most frequent variant of Guillain-Barré syndrome was demyelinating polyneuropathy (67.4%), followed by acute axonal neuropathy (7.0%), Miller Fisher syndrome (7.0%), Bickerstaff brainstem encephalitis (7.0%), pharyngo-cervical-brachial variant (4.7%), and polyneuritis cranialis (4.7%). Follow-up revealed that 35 recovered satisfactorily, eight were persistently disabled, and none died during hospitalization. At the earliest stage, differentiating clinical variants from typical Guillain-Barré syndrome was difficult. Children with clinical variants of Guillain-Barré syndrome are more likely to manifest rapid onset from disease onset to nadir, increasing the severity of disability, cranial nerve involvement, urine incontinence, respiratory impairment, and need for ventilator support than in typical Guillain-Barré syndrome.

Therapeutic Hypothermia for Febrile Infection-Related Epilepsy Syndrome in Two Patients

Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most important cause of mortality and neurologic deficits during childhood. Only a few therapeutic agents were reported to shorten the acute phase and improve outcomes. Therapeutic hypothermia was reported effective in stabilizing immune activation, brain edema, and seizure activity, to protect the brain from ongoing functional, apoptotic neural, and glial damage and the systemic expansion of the cytokine storm. We present two pediatric cases of febrile infection-related epilepsy syndrome, refractory to conventional medical therapy. Moderate therapeutic hypothermia at 33°C resulted in fast, sustained control of refractory status epilepticus. After 3 months, both patients recovered with a Glasgow Outcome Scale score of 4. Therapeutic hypothermia may play an important role in children with febrile infection-related epilepsy syndrome.

Effect of topiramate, in combination with lidocaine, and phenobarbital, in acute encephalitis with refractory repetitive partial seizures

OBJECTIVE Acute encephalitis with refractory repetitive partial seizure (AERRPS) is a peculiar type of post-encephalitic/encephalopathic epilepsy. Here we report an analysis of AERRPS in a series of children and propose an effective treatment option for seizure control in these children. METHODS We retrospectively reviewed cases of AERRPS treated in a pediatric intensive care unit, between February 2002 and June 2006. Clinical characteristics were systemically assessed. Burst suppression coma was induced by high-dose suppressive therapy; 24-h electroencephalogram (EEG) monitoring was performed on each patient. The goal of treatment was to achieve complete clinical seizure control or burst-suppression pattern on EEG, aiming for an interburst interval of >5s. Brain imaging was done for each patient. RESULTS There were nine patients (seven boys), aged 5-15 years. Clinical symptoms included fever (100%), upper respiratory symptoms (66.7%) and altered consciousness (66.7%). All patients received multiple high-dose suppressive drugs and were intubated with/without inotropic agents. Seizures in three patients were stopped after high-dose lidocaine infusion (6-8 mg/kg/h) in the acute stage and three patients were stopped after high dose phenobarbital (serum level 60-80 ug/mL) combined with high-dose oral topiramate (15-20 mg/kg/day). Follow-up for this study was 16-61 months. Two subjects died while seven developed epilepsy and/or neurologic deficits; none returned to baseline. All survivors were discharged and continued multiple antiepileptic medications. CONCLUSIONS Our data indicates that children with AERRPS have high mortality and morbidity rates. High-dose topiramate combined with high-dose lidocaine infusion or high-dose phenobarbital in the acute stage might be an effective treatment option for children with AERRPS.

Analysis of convulsive status epilepticus in children of Taiwan.

Convulsive status epilepticus is a medical emergency with significantly associated mortality and morbidity. The demographic data and outcomes of convulsive status epilepticus in children were collected for descriptive analysis. We retrospectively reviewed cases of convulsive status epilepticus in the Pediatric Intensive Care Unit of Chang Gung Childrens Hospital between 1999 and 2006. We enrolled 141 patients with 198 episodes of convulsive status epilepticus, aged 2 months to 18 years: 24.8% of first episodes developed convulsive status epilepticus, with a duration of over 60 minutes. First episodes of convulsive status epilepticus were most often evidenced in febrile status during acute central nerve system infections (48.2%), and in nonfebrile status during acute noncentral nerve system illness in previously epileptic children (28.4%). Before their first episode, 63.8% of children were neurologically healthy, and 12.2% exhibited a prolonged febrile seizure. The most common etiology of mortality was acute central nervous system infection. The immediate mortality rate was 7.1%. Convulsive status epilepticus in childhood is more common, with a different range of causes and a lower risk of death, than convulsive status epilepticus in adults. Acute central nervous system infections appear to be markers for morbidity and mortality.

Risk factors and outcomes of childhood ischemic stroke in Taiwan

In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke.