Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics.

AIM: This study investigated the efficacy and safety of perampanel (PER) adjunctive therapy in pediatric patients with epilepsy whose seizures are pharmacoresistant to existing antiepileptic drugs. METHODS: A clinical retrospective study was conducted from 2016 to 2017 in the pediatric neurology clinic at a tertiary children's hospital. We reviewed the data obtained from 66 children whose seizures were pharmacoresistant to more than two antiepileptic drugs, and could be followed up for a minimum of 3 months after PER adjunctive therapy initiation. The efficacy was estimated by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and adverse events were also recorded. RESULTS: The rate of seizure reduction of >50% was 30.3%, 37.5%, and 34.7% for all seizure types at 3, 6, and 12 months, in which 7.6%, 8.9%, and 14.3% of the patients became seizure-free at these time points, respectively. No significant differences were found between enzyme-inducing and nonenzyme-inducing antiepileptic drugs in combination with PER with regard to the responder rate. Five patients with Dravet syndrome were included in the study. Four of them (80%) exhibited 50% seizure reduction at the last visit, at which point, two patients (40.0%) were seizure-free. The retention rate was 51% at 12 months. Adverse events were documented in 25 patients (35.7%) and led to PER discontinuation in eight patients (12.1%). The most common adverse events comprised irritability, skin rash, dizziness, and somnolence; however, all were transient and successfully managed after PER dose reduction or discontinuation. CONCLUSION: The current data support the value of adjunctive PER in child and adolescent patients with pharmacoresistant epilepsy in daily clinical practice. Perampanel was efficacious and generally well-tolerated as an add-on treatment for epilepsy.

Schizencephaly in children: A single medical center retrospective study.

BACKGROUND: The aim of this study was to evaluate the clinical, and neuroimaging features, outcomes, and other associated systemic disorders in children with schizencephaly at a single medical center in Taiwan. METHODS: We retrospectively reviewed the medical records and magnetic resonance images (MRI) of children with schizencephaly between January 2000 and December 2014. The MRI findings of schizencephaly were recorded along with the presence of associated cerebral disorders. Clinical, electroencephalographic and additional systemic disorders were also recorded. RESULTS: A total of 21 patients (13 males and 8 females) were included in the study. According to the location of schizencephaly, the patients were classified into two groups: unilateral (n = 16) and bilateral (n = 5). The majority of the patients with neurological deficits were detected before 1 year of age, especially in bilateral clefts. The most common initial presentation was hemiparesis in unilateral schizencephaly, and seizures in bilateral schizencephalies. Ventriculomegaly was the most common associated cerebral disorder, and the most common additional systemic disorders included congenital heart disease, hydronephrosis, and strabismus. Seventeen patients suffered from epileptic seizures with generalized tonic-clonic seizures being the most common. Eight patients developed refractory epilepsy. The majority of the patients had motor deficits, intellectual disabilities, and language deficits, especially in bilateral clefts. CONCLUSIONS: This study demonstrates that the clinical features of schizencephaly vary widely, with their severity closely related to the cleft. Determining the type, size, and extent of schizencephaly is useful to plan management and predict the prognosis.

Primary spinal tumors in childhood: A single institution 15 year experience.

BACKGROUND: Pediatric primary spinal tumors (PST) are fairly uncommon, with little available data regarding incidence and outcomes. MATERIALS AND METHODS: We conducted a retrospective review of the 22 consecutive patients less than 18 years old diagnosed with PST between March 1997 and May 2011 and treated at Chang Gung Children Hospital. All patients had undergone magnetic resonance imaging (MRI) for pre-operative evaluation and operations for PST. The extent of tumor removal was assessed by surgical report by the neurosurgeon or by post-operative MRI if available. RESULTS: Ten of them had intramedullary tumors and 12 had intradural extramedullary tumors. All patients were treated with surgery to the primary site. A total of 15 patients underwent gross total tumor resection and seven patients received post-operative radiotherapy. Five patients received adjuvant chemotherapy for their primary tumor. Fourteen patients (64%) survived from study entry without tumor progression. CONCLUSIONS: PST encompassed a diverse group of pathologic entities that differ markedly based on the location and age of the children. Total resection of pediatric PST in children could be performed with acceptable risk and satisfactory long-term results.

Clinical and neuroimaging findings in children with gray matter heterotopias: A single institution experience of 36 patients.

OBJECTIVE: To describe the clinical spectrum and neuroimaging features of childhood gray matter heterotopias in a single tertiary hospital in Taiwan. METHODS: We retrospectively reviewed the medical records and magnetic resonance images (MRI) of 36 patients with gray matter heterotopias, 19 females and 17 males, between July 1999 and June 2014. The MRI morphologic findings of gray matter heterotopias were recorded along with the presence of associated cerebral malformations. The clinical, electrophysiological and associated systemic malformation data were also recorded. RESULTS: A total of 36 patients were included in the study. Their ages ranged from 1 month to 18 years with a mean age of 3 years 6 months. According to the location of gray matter heterotopias, patients were classified into two groups: periventricular (26) and band (10). The phenotypic spectrum in our population differed from that described previously. In the periventricular group, additional cerebral malformations were found in 18/26 (69%) and systemic malformations in 14/26 (54%). In the band group, additional cerebral malformations were found in 5/10 (50%) and systemic malformations in 2/10 (20%). The majority of patients had developmental delay and intellectual deficit. Twenty-two patients suffered from epileptic seizures with 12 developing refractory epilepsy. CONCLUSIONS: In periventricular heterotopias, the most common associated cerebral malformation was ventriculomegaly, followed by agenesis of corpus callosum. Congenital heart disease was the most common additional systemic malformation. However, the most common associated cerebral malformation was pachygyria in band form. The majority of patients had developmental delay, intellectual deficit, especially in band heterotopias.

Risk factors of respiratory failure in children with Guillain-Barré syndrome.

BACKGROUND: Respiratory failure is rarely associated with Guillain-Barré syndrome (GBS) in children. The aim of the study was to determine the risk factors of respiratory failure in children with GBS to advance management. METHODS: In this retrospective study, the variables that lead to respiratory failure were investigated in 40 children. The risk factors were compared for 4 children with intubation and 36 without. We also analyzed the specific treatments, including corticosteroids, intravenous immunoglobulin, plasmapheresis, and clinical status at discharge. RESULTS: Four (10.0%) of the 40 children with GBS required mechanical ventilation. The need for mechanical ventilation was significantly related to the Hughes score at nadir (p<0.001), respiratory distress (p<0.001), and hypotension (p<0.001). Atypical presentation of symptoms such as croup, hoarseness, vomiting, ataxia, consciousness disturbance, and previous event of diarrhea were more predominant in patients younger than 6 years. Disability grades >3 at discharge were found in 15 patients (37.5%), and there was no mortality in the present case series. CONCLUSIONS: Respiratory failure in childhood GBS was related to the Hughes score at nadir, respiratory distress, and hypotension. Atypical presentations of symptoms were more predominant in patients younger than 6 years. The prognosis in our series was good and not related to previous events. Understanding the risk factors of severe GBS will provide better treatment strategies and improve the outcomes.

Acute disseminated encephalomyelitis in children: a single institution experience of 28 patients.

The aim of this study is to describe the clinical, laboratory, and neuroimaging features, treatment and outcome of acute disseminated encephalomyelitis (ADEM) in Taiwanese children to compare with two series from United States of America and Japan. We retrospectively reviewed the medical records and magnetic resonance images of 28 children, 23 boys and 5 girls, with ADEM between January 2001 and December 2009. Their mean age at disease onset was 6 years 9 months. Twenty four children experienced a prodromal illness. There was no special seasonal distribution in our patients. They presented mostly with impaired consciousness and headache. Cerebrospinal fluid samples of 21 patients were analyzed and none showed intrathecal oligoclonal bands. Magnetic resonance imaging showed variable findings: lesions with abnormal signal changes frequently found in the subcortical white matter of frontal and parietal lobes. No patient showed cortical gray matter involvement. We also found a high rate of deep gray matter involvement including thalami and basal ganglia. Treating with steroids was usually associated with a rapid recovery and both intravenous high dose methylprednisolone and dexamethasone had the same effect. All patients survived. Twenty three patients recovered completely with only mild sequelae in the remaining five children.

Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy.

BACKGROUND: Acute seizures are readily recognizable episodes requiring urgent treatment. This study was conducted to compare the efficacy and safety of suppository use of rectal diazepam solution [Stesolid rectal tube (SRT), Alpharma, Inc., Lierskogen, Norway] with those of intravenous diazepam (IVD), Li Ta Pharma Co, Ltd., Taichung, Taiwan for control of acute seizures in children with intractable epilepsy. METHODS: Subjects were patients, aged 1-18 years, with intractable epilepsy under at least three kinds of antiepileptic treatments. Caregivers were trained to rectally administer SRT or IVD (dosage varying from 0.2 to 0.5mg per kilogram of body weight) and to monitor respiration condition, seizure severity, and adverse drug effects. RESULTS: Among the 24 subjects, 9 males and 15 females, treated for a period of 3 months, the ages ranged from 2 to 18 years, with a mean of 9.1 years. Seizure types were generalized tonic and/or clonic. Seizure frequency varied from once per week to 20 times per day. Twenty-one (87.5%) of them had mental retardation and/or developmental delay, and 103 of the 127 (81.1%) IVD administrations and 90 of the 103 (87.3%) SRT administrations resulted in rapid cessation of seizures within 10 minutes. Each first dose failed to control seizures in 24 and 13 episodes, respectively. A second dose of IVD achieved cessation of seizure in 21 of the 24 episodes and a second dose of SRT in 12 of the 13 episodes within another 10 minutes. Four episodes (3 with rectal IVD and 1 with SRT) of prolonged seizure beyond 20 minutes needed IVD injection at our emergency room. Sedation occurred in 17% of patients, which was attributed to IVD in 8% and SRT in 9% of patients. No respiratory depression was attributable to IVD or SRT. There was no significant statistical difference in efficacy and safety between these two forms of diazepam. CONCLUSION: Rectal diazepam solution, administered by capable caregivers, is as effective and safe as rectal administration of IVD for children with intractable epilepsy.

Immunologic analysis and serum heavy metal levels in exacerbated Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset and relapsing disorder characterized by involuntary simple or complex tics and high co-morbidity with behavioral anomalies. Its pathophysiologic mechanisms remain unclarified. We investigated immunologic alternations and serum heavy metal levels in patients with TS to elucidate the unclarified mechanisms. Based on the Yale Global Tic Severity Scale, fifteen TS subjects (four females) aged 8-34 (mean: 15.4 +/- 6.7) in exacerbation with mean severity score 40.3 +/- 14.6 were enrolled in this study. The immunoglobulin levels were normal except for higher immunoglobulin E levels (in 10 patients) with atopy. In exacerbation, there were reverse CD4/CD8 (in two), higher percentages of natural killer cells (in five) and memory T cells (in eight), diminished lymphocyte activation CD69 marker (in three) and impaired NK cytotoxicity (in six) that showed a trend of lower inhibitory CD94 (NKG2A), activating NKp46, and perforin expression compared to those of patients with stable TS and healthy controls, but similar granzyme expression. Serum ASLO, mycoplasma antibody and the levels of heavy metals were not significantly different. All aforementioned immune alterations returned to the normal ranges except for the consistently higher memory T cells. Our study demonstrated that, in some patients with TS, consistently higher memory T cells and lower cytotoxicity in exacerbation status reflect immune alterations and underscore the potential for immunomodulation or immunosuppressive treatment.

Tuberous sclerosis complex with multiple intracranial aneurysms in an infant.

Tuberous sclerosis complex is a protean, genetically determined disease that may involve any organ or tissue and lead to a great number of signs and clinical features. Occlusive vascular disease and aneurysms of the cerebral and visceral arteries were described in these patients. We report on an 8-month-old boy who manifested tuberous sclerosis complex with multiple intracranial aneurysms involving the internal carotid artery and middle cerebral artery. The unusual features of our case favor the concepts of the presence of an arterial dysplasia in tuberous sclerosis complex, and of developmental defects as the cause of intracranial aneurysms.

Clinical experience of childhood hypertensive encephalopathy over an eight year period.

BACKGROUND: Hypertensive encephalopathy is an uncommon neurological syndrome in children, usually with reversible clinical and neuroimaging findings. Little is known about the precipitating factors, clinical presentations, neuroimaging findings and outcomes of childhood hypertensive encephalopathy in Taiwan. METHODS: To characterize this syndrome, we retrospectively analyzed 12 children with hypertensive encephalopathy in a tertiary institution from 1998 through 2005. We investigated the precipitating factors, clinical findings, courses, neuroimaging characteristics and outcomes. RESULTS: Twelve patients (10 boys and 2 girls) with hypertensive encephalopathy were identified. Post-streptococcal glomerulonephritis was the most common precipitating underlying disease. Common clinical presentations included mental change (100%), seizure (91.6%), headache (66.6%), nausea or vomiting (75%), and blurred vision (41.6%). Brain imaging studies showed vasogenic edema over the bilateral parietal, occipital and parasagittal regions, or the cerebellum. All patients had a reversible clinical course. CONCLUSION: Hypertensive encephalopathy is predominant in males, and mental change is the most common clinical presentation. Renal origin is a common precipitating factor. A characteristic lesion of hypertensive encephalopathy is occipitoparietal region edema. The overall clinical outcome is good after prompt treatment.

Sonography for detection of spinal dermal sinus tracts.

OBJECTIVE: It is well known that spinal dysraphism may be complicated by meningitis as a result of infection traveling from the skin along a patent dermal sinus tract. The only clue is the lower back cutaneous lesions. Our aim was to investigate the correlation between cutaneous lesions, patent dermal sinus tracts, and spinal dysraphism and their complications. METHODS: Five patients (3 female and 2 male) with spinal patent dermal sinus tracts were studied. We used a 7-MHz linear transducer with a two-dimensional real-time sonographic system to insonate and obtain transverse and longitudinal views of the spinal cord and subcutaneous area, extending from the cervical cord to the sacral areas. Subsequently, we performed spinal magnetic resonance imaging in every patient to confirm the diagnosis and to evaluate the intraspinal conditions. RESULTS: The associated central nervous system anomalies and complications were tethered cords (n = 5), dermoid cysts (n = 3), lipoma (n = 2), central nervous system infections (n = 2), and syringomyelia (n = 1). The outcomes were better in those who received surgical intervention before they were infected. CONCLUSIONS: Early detection of spinal patent dermal sinus tracts and related anomalies was accomplished with spinal sonography and allowed for prophylactic treatment (e.g., early surgical intervention) before the onset of neurologic deficits.

Transcranial ultrasound diagnosis of intracranial lesions in children with headaches.

The diagnostic value of transcranial ultrasound for intracranial lesions in children with headaches was evaluated. From January 1995 to December 1998, 444 children with headaches for more than 2 weeks visited our Pediatric Neurologic and Neurosurgical Outpatient Clinics. A 2-MHz-sector sonographic transducer was used to perform transcranial ultrasound. Nineteen patients were lost to follow-up. Two patients, both 15 years of age, failed to have a successful examination. Thirteen of the enrolled 423 patients presented with headaches and other symptoms and positive neurologic signs and had positive magnetic resonance imaging findings of intracranial lesions correlating with their transcranial ultrasound findings. Twelve of the remaining 410 children complaining of isolated headache had abnormal transcranial ultrasound findings. Nine of the 12 patients were confirmed to have intracranial lesions by magnetic resonance imaging studies. Among the nine patients, five had brain tumors, two patients had hydrocephalus, one patient had intracerebral hematoma, and one patient had temporal arachnoid cyst. The other three patients were misinterpreted to have a suprasellar lesion by transcranial ultrasound. These three patients and the remaining 398 children were regularly followed for at least 12 months. All revealed no evidence of an intracranial lesion. The sensitivity and specificity of transcranial ultrasound to detect intracranial lesions for children with isolated headaches were 75% and 99.7%, respectively. The average saving from utilizing this technique was $222 U.S. dollars per person. We suggest that transcranial ultrasound study is a reliable, convenient, time-saving, and economic diagnostic tool in detecting intracranial lesions in children with headaches.