Jainn-Jim Lin

Adenovirus Serotype 3 and 7 Infection with Acute Respiratory Failure in Children in Taiwan, 2010–2011

Objective Increased incidence of adenovirus infection in children was noticed since September 2010 in Taiwan and severe cases requiring intensive care were noted later. We did this study to find the clinical characteristics and risk factors associated with severe adenovirus infection. Patients and Methods We collected cases of severe adenovirus infection between November 2010 and June 2011 to analyze their clinical characteristics in two medical centers in northern Taiwan. Severe adenovirus infection was defined as laboratory-confirmed adenovirus cases with required intensive care. Hexon gene sequencing was performed for molecular genotyping. Results 45 patients were included, 22 cases (49%) were infected with serotype 7, 19 (42%) with serotype 3, and 4 with serotype 2. The median age (range) was 2.75 years (0.08–15.43 years); 87% were below 5 years. Male to female ratio was 1.65 (28 to 17). Of these patients, 56% had underlying neurological diseases, 50% experienced fever higher than 40°C and 69% suffered fever longer than one week. The clinical diagnosis included pneumonia in 40 (89%) patients, bronchopneumonia in 5 (11%), and encephalitis in 7 (16%). At least 22 patients had pleural effusion. They had complications of respiratory failure (53%), acute respiratory distress syndrome (24%), hypotension (40%), and 6 (13%) patients needed extracorporeal membranous oxygenation. Ten (22%) patients died, all with underlying major systemic diseases and 7 (70%) infected with serotype 7. Conclusions Adenovirus serotype 7 and 3 can cause severe disease–even death–in children, especially those with underlying neurological diseases. Patients infected with adenovirus serotype 7 tended to have a higher case-fatality rate.

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.

Rapid progression and brain atrophy in anti-AMPA receptor encephalitis

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis that is rarely reported. Our study evaluated the first known patient who developed anti-AMPA receptor encephalitis during pregnancy. Initial brain MRI revealed bilateral limbic encephalitis. However, rapid brain atrophy on MRI with extensive hypometabolism of cerebral cortices, caudate nuclei and brain stem hypoperfusion on (18)F-FDG PET developed when clinically progressed. IgG index of serial CSF studies reflected the clinical improvements after plasmapheresis and plasma exchange. The clinical spectrum of anti-AMPA receptor encephalitis may be expanded from limited limbic involvement to extended central nervous system.

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.

Therapeutic Hypothermia Associated With Increased Survival After Resuscitation in Children

Brain injury after resuscitation is associated with high morbidity and mortality in children. Therapeutic hypothermia has theoretical benefits on brain preservation. It has been shown to be effective in improving neurological outcomes after adult ventricular arrhythmia-induced cardiac arrest and neonatal asphyxia. However, there have only been a few reports about therapeutic hypothermia after pediatric resuscitation. We conducted this retrospective cohort study in a tertiary pediatric intensive care unit between January 2010 and June 2012. All children from 2 months to 18 years of age with resuscitation and a history of at least 3 minutes of chest compressions with survival for 12 hours or more after return of circulation were eligible. Forty-three patients met the eligibility criteria for the study. Forty-two patients (97.6%) were asphyxial in etiology; 29 (67.4%) of them occurred out-of-hospital. Excluding one child with cardiac etiology, the overall survival rate to hospital discharge was 57.1%. Fourteen (33.3%) patients received hypothermia therapy and were cooled to 33°C for 72 hours. The survival rate was higher in the therapeutic hypothermia group (11/14, 78.6%) than in the normothermia group (13/28, 46.4%). In conclusion, therapeutic hypothermia was associated with increased survival rate after pediatric resuscitation.

Seizures in childhood ischemic stroke in Taiwan

In this retrospective study, we collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of seizure after ischemic stroke for the period of January 1996 to July 2006. Thirty-nine out of 94 children with ischemic stroke had poststroke seizures. Thirty-three out of 39 children with poststroke seizures had new onset seizures but only data of 28 were available. Infection was the most common etiology in the early poststroke seizure group (52.4%) but not in the late poststroke seizure group (0%). Infarction involving arterial ischemic stroke of anterior circulation were the most common in both the early poststroke seizure (61.9%) and the late poststroke seizure group (57.1%). Epilepsy was the most common sequelae in both the early poststroke seizure (38.1%) and late poststroke seizure group (100%). Children who had initial focal neurological sign (100% vs. 38.1%; P=0.007) or the focal cortical dysfunction on EEG (85.7% vs. 33.3%; P=0.029) were prone to develop late poststroke seizures. Late poststroke seizures had a high risk of developing poststroke epilepsy (100% vs. 38.1%; P=0.007). We conclude that seizures commonly occur in childhood ischemic stroke. Most poststroke seizures developed at an early stage. Infection was the most common etiology that caused early poststroke seizures in childhood ischemic stroke. Initial focal neurological signs and focal cortical dysfunction on EEG are risk factors for developing epilepsy. Poststroke seizures did not affect mortality, but there was a significant difference in normal outcome and epilepsy between those with or without poststroke seizures.

Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome in Children

Central diabetes insipidus, a common consequence of acute central nervous system injury, causes hypernatremia; cerebral salt wasting syndrome can cause hyponatremia. The two conditions occurring simultaneous are rarely described in pediatric patients. Pediatric cases of combined diabetes insipidus and cerebral salt wasting after acute central nervous system injury between January 2000 and December 2007 were retrospectively reviewed, and clinical characteristics were systemically assessed. Sixteen patients, aged 3 months to 18 years, met study criteria: 11 girls and 5 boys. The most common etiologies were severe central nervous system infection (n = 7, 44%) and hypoxic-ischemic event (n = 4, 25%). In 15 patients, diabetes insipidus was diagnosed during the first 3 days after acute central nervous system injury. Onset of cerebral salt wasting syndrome occurred 2-8 days after the onset of diabetes insipidus. In terms of outcome, 13 patients died (81%) and 3 survived under vegetative status (19%). Central diabetes insipidus and cerebral salt wasting syndrome may occur after acute central nervous system injury. A combination of both may impede accurate diagnosis. Proper differential diagnoses are critical, because the treatment strategy for each entity is different.