ROUTINE STUDY IN TUBEROUS SCLEROSIS FOLLOW-UP

Tuberous sclerosis complex (TSC) is a rare disease. But the patients and their family of TSC in Taiwan had organized the association of Taiwan Tuberous Sclerosis complex to share the care of the patient's condition. The most important influence about follow-up is the manual for the patient.

The high incidence of seizure attack in TSC patients contribute to the high rate of the follow-up by pediatric neurologist. The clinical conditions of TSC are related to multiple system, esp. the brain, heart and kindey. So we need to know about the suggested follow-up study in the manual and may re-organize the corrected follow-up study for TSC.

Although there are many papers with suggestion about TSC follow-up, the variable considerations between the patients and between the family should be reasonable. This is a hint to how follow the TSC patient with corrected study and timetable.

Cranial MRI scan is more prefered for TSC follow up than CT scan and performed annually to adult age. Cardioechography should be performed annually to at least adult age and then by indication. Echography for kindey should be considered about puberty, the present and size of angiomyolipomas and the intervention for angiomyolipomas. If large angiomyolipomas or symptomic patient is noted, MRI scan for kindey is indicated.

At diagnosis, Neurodevelopmental testing, OPH examination, electrocardiography, cardioecography, Kidney echography and Cranial MRI (or CT) should be arranged.

In the future, we hope to set up the multiple hospital cooperation for long term follow up of TSC patients in Taiwan.

DISORDERS OF BALANCE AND MOVEMENT: NON-PHARMACOLOGICAL STRATEGIES FOR CHILDREN WITH TIC AND TOURETTE DISORDERS

There is no cure for tic and Tourette disorders (TTD) at present.

Pharmacological regimens are mostly symptomatic suppression and of off-level use.
Surgical treatment such as deep brain stimulation is still under experimental trials. There must be some strategies for children with TTD to cope with their daily and chronic tics and associated problems:

1. Accurate awareness and positive attitude.
2. Excessive physical and/or mental activity
3. Control of food that may exacerbate tics
4. Control of infection and allergy
5. Well posture control
6. Sleep hygiene
   1. inattention-hyperactivity-impulsivity
   2. obsession-compulsion
   3. self-injury
   4. others

We are going to have a consensual viewpoint about the above issues after this discussion.

GRAY AND WHITE MATTER DEGENERATIVE DISORDERS

There are many reported gray and white matter degenerative disorders in infancy and childhood. The hallmark of these CNS degenerative disorders is the progressive devastation of formally given competences. In infants and young children, a decelerated milestone of development is often the initial manifestation. Subsequently the child falls progressively behind other children and loses previously acquired milestones.

Generally, CNS degenerative disorders are attributed into three divisions clinically:
gray-matter diseases, white-matter diseases, and system-associated diseases. We highlight on the current proceedings of gray and white matter degenerative disorders in infancy and childhood and reviewed the previous articles and cases of gray and white matter degenerative disorders reported in Taiwan.

Based on published reports in literatures of current twenty years, gray and white matter degenerative disorders including Rett syndrome (8), neuronal ceroid lipofuscinosis (Late infantile type:3, juvenile type:3), Pantothenate kinase-associated neurodegeneration (4), Menkes' kinky hair disease (3). White matter degenerative disorders in Taiwan were
reported as X-linked adrenoleukodystrophy (X-ALD) (9) , metachromatic leukodystrophy (MLD) (2), neonatal adrenoleukodystrophy (NALD) (1), probable Pelizaeus-Merzbacher disease (P-M disease) (1), Alexander disease (1), Cockayne syndrome (3).

A large group of mitochondrial diseases (e.g. MELAS, Leigh disease, MERRF etc) and some groups of systemic storage diseases (e.g. Krabbe disease, MPS etc) related gray and white matter degenerative disorders were not enrolled in this subject for analysis; however, further investigations should be approached in the near feature.

In conclusion, we believe that these published cases may represent just the tip of iceberg. To establish registration systems and data bank of gray and white matter degenerative disorders for Taiwan Child Nerve Society is urgent nowadays and also being our sincere anticipation.

INFECTIONS OF THE NERVOUS SYSTEM

Infections of the nervous system can be classified according to the infection sites, pathogens or pathophysiology. Among the central nervous system infections, meningitis can be caused by viruses, bacteria, or parasites; while encephalitis usually is caused by direct viral invasion or autoimmune response.

In Taiwan, there are lots of reports concerning the nervous system infections.
However, nationwide or multicenter studies are still limited. Taiwan Child Neurology Society could conduct related studies especially focus on image findings of neonatal meningitis, neurologic findings of new emergent infections, long term outcome of nervous system infections, etc. However, manpower and fund need to be resolved before the cooperation.

ESTABLISH A PROTOCOL OF MULTIDISCIPLINARY CARE FOR PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

Duchenne muscular dystrophy (DMD) is a severe, progressive muscular disease that affected 1 in 3,600-6,000 live male births. Almost all individuals can have mildly delayed motor milestones and are unable to run and jump properly due to proximal muscle weakness since early childhood. Most DMD patients are diagnosed at approximately 5 years of age. Untreated, muscle strength deteriorates, and boys require the use of a wheelchair before their teens. Respiratory, orthopaedic, and cardiac complications emerge, and without intervention, the mean age at death is around 19 years.

Optimum management of DMD requires a multidisciplinary approach that focuses on anticipatory and preventive measures as well as active interventions to address the primary and secondary aspects of the disorder. Implementing comprehensive management strategies can favourably alter the natural history of the disease and improve function and
quality of life.

Although guidelines are available for various aspects of DMD, however, comprehensive clinical care recommendations and consensus had not been made in Taiwan.
We modified the DMD Care Considerations Working Group (Bushby K et al. Lancet Neurol 2010;9:77-93 & 177-89), evaluated assessments and interventions used in the managements of diagnostics, diagnostic interventions, gastroenterology and nutrition,
rehabilitation, neuromuscular, psychosocial, cardiovascular, respiratory, orthopaedic, and surgical aspects of DMD. These recommendations are intended for the wide range of practitioners who care for individuals with DMD. They provide a framework for recognizing the multisystem primary manifestations and secondary complications of DMD
and for providing coordinated multidisciplinary care.

With collaboration with pediatric neurologists in Taiwan, we try to form consensus and establish a protocol of multidisciplinary care for patients with DMD to improve their quality of life, health and longevity, with the aim to children who are diagnosed today having the possibility of a life expectancy into their fourth decade.

BRAIN INJURY AND DISORDERS OF CONSCIOUSNESS

Consciousness is the awareness of self and environment. Impairment of consciousness can be divided into activated or reduced mental states. The former includes hallucination, delusion and delirium, while the latter contains obtundation, stupor, coma, vegetative state and brain death. The best known scale to evaluate the consciousness is the Glasgow Coma Scale (GCS), which yields a score of 3 to 15 based on best response to stimuli in the following three categories: eye opening, verbal response and motor response. The original GCS was not suitable for the assessment of newborns, infants and younger children, and several alternate scales have been proposed, among which the Glasgow Coma Scale-Modified for Children allows the best comparison with the GCS.

Brain death, one unique status of impairment of consciousness, is permanent absence of all brain functions, including those of brainstem. Brainstem dead patients are irreversibly comatose and apneic with absence of all brainstem reflexes. In Taiwan, the guideline for determination of brain death in children was established in 2004 which only approved
for above 3 years of age. Facing the fact that there has been increasing demand for the establishment of criteria for diagnosis of brain death in young children, further revision of the current guideline is mandatory.

Brain injury in children includes traumatic and non-traumatic origins. Traumatic brain injury (TBI) is the leading cause of death and disability in children. Moderate and severe pediatric traumatic brain injury has been associated with long-standing cognitive, neurologic and behavior impairment. TBI in children has been regarded as a significant public health problem in the world. Health-care providers should take every chance to provide important information and education to the caregivers.

Hypoxic-ischemic encephalopathy is the major etiology of nontraumatic brain injury.
A cascade of events will be developed by global ischemia, including ATP reduction, glutamate release, activation of NMDA and non-NMDA receptors, calcium influx and activation of secondary messengers. Recent advances of management refer to multi- modality approaches in the blockade of the hypoxic cascades.

We will propose a registry policy of traumatic brain injury and that of brain death to conduct the multicenter study to collect the clinical and relevant information for those children suffering from TBI and brain death in Taiwan.

EPILEPSY AND THE ROLE OF TAIWAN CHILD NEUROLOGY SOCIETY: THE PAST, THE PRESENT AND THE FUTURE

On behalf of committee for epilepsy research, Taiwan Child Neurology Society, I am here to express the purpose of the establishment of this committee and the goals we will try to reach.

Brief history of epilepsy will be presented. The roles of pediatric neurologists of Taiwan Child Neurology Society in the promotion of epilepsy research will be mentioned.
And then I will focus on the future: What shall we, the Taiwan Child Neurology Society, do after what we have done in the past? Where shall we go from where we stand now? Which are the goals we shall pursuit after those we have achieved?

To be more specific, long-term prospective and collaborative study or work for the following aspects of epilepsy by colleagues of Taiwan Child Neurology Society will be mentioned: Epidemiological study, individualized medicine, alternative treatment, and educational program.

ESTABLISHING STANDARD OF CARE FOR NEUROMUSCULAR DISORDERS BY INTERNATIONAL CONSORTIUMS

Pediatric neuromuscular disorders are a group of rare diseases that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis and advances in medical technology for these disorders have not been matched by similar developments in the clinical care for them. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. Three International Standard of Care Committees for spinal muscular atrophy (SMA), congenital muscular dystrophies (CMD) and congenital myopathies (CM) have worked together to develop practice guidelines for the clinical care of these patients.

The Standard of Care Committees for SMA was formed in 2005. The 60 committee members worked through conference calls, e-mail communications, Delphi survey, and 2 in-person meetings to review literature and achieve consensus on 5 care areas:
Diagnostic/New Interventions, Pulmonary, Gastrointestinal/Nutrition, Orthopedics/ Rehabilitation, and Palliative Care. The Consensus Statement on the Standard of Care for SMA was published in 2007.

The International Standard of Care Committee for Congenital Muscular Dystrophy was established in 2009 to identify current care issues, review literature for evidence- based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation,gastroenterology/nutrition/speech/oral
care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3- day workshop conducted in Brussels, Belgium, in November 2009. The Consensus Statement on Standard of Care for CMD was published in 2010.

The International Standard of Care Committee for Congenital Myopathies was formed in 2009. The Committee includes 59 members from over 10 different medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation.
The members of the Committee worked through frequent e-mail correspondences, periodic conference calls, two rounds of on-line surveys, and a three-day workshop at Stanford University to achieve a consensus for diagnostic and care recommendations. Two papers have been submitted for publication, one on the diagnostic and one on clinical care
guidelines which include symptom monitoring and therapeutic interventions.

It is the goals of these Committees that through the dissemination of these care guidelines patients with euromuscular disorders will receive early and accurate diagnosis and optimal clinical care.

THE EVOLUTION OF HYPSARRHYTHMIA IN EEG IN INFANTILE SEIZURES: ETIOLOGY, SEIZURE TYPES AND PROGNOSIS

Background and Objectives: To examine the associated seizure types, underlying causes, outcomes and the EEG evolutions of hypsarrhythmia in infantile seizures. Methods: This retrospective study enrolled all EEG records performed from Jan 2003 to Dec 2010 with patterns of hypsarrhythmia. Variables such as type and etiology of seizures, onset age and persisted duration of hypsarrhythmia, EEG evolutions, and AED efficacy were analyzed.

Results:> A total of 62 patients with hypsarrhythmia in EEG among 14,826 EEG records was enrolled. Among them, around 73% was symptomatic and brain injury (19/62, 31%) was the leading cause. However, around 27% of patients had unknown etiology. Nearly all patients presented with infantile spasms and only few patients presented with
myoclonic jerks. Nearly all patients had EEG evoluted to multifocal and generalized epileptiform discharges after treatment. The hypsarrhythmia in EEG may persist for 2 weeks to 2 years after treatment, but some patients had persistent hypsarrhythmia for 3-5 years. Nearly all patients with hypsarrhythmia were under at least 2 anti-epileptic
drug (AED) treatment, and over half of the patients were under more than 3 AED treatment.

Discussion: The etiology of hypsarrhythmia can be found in around 73% of the patients. Hypsarrhythmia in most patients finally evolved into multifocal and generalized epileptiform discharges, and above half of patients need more than 3 AEDs for seizure control.

PROGNOSTIC FACTORS OF DEVELOPMENTAL OUTCOME IN NEONATAL SEIZURE

Background and Objectives: To identify prognostic indicators of neurodevelopmental outcome in infants who experienced clinical neonatal seizure.

Methods: This is a retrospective, observational hospital-based study. Infants who experienced clinical neonatal seizure between Jan 2005 and Dec 2009 were enrolled.
Adverse outcomes were defined as death, cerebral palsy, global developmental delay, and/or epilepsy. The association between adverse outcomes and twelve variables were analyzed, including small of gestational age, method of delivery, prematurity, presence of meconium aspiration, antenatal insults, or perinatal insults, Apgar score at 5 min, seizure onset, seizure type, EEG epileptiform activity, anticonvulsant therapy efficacy, and etiology. Pearson Chi-square and Fisher's exact test were used to evaluate the prognostic indicators.

Results: Among the 125 enrolled infants, 60 infants had normal outcome, and 40 survived with one or more neurodevelopmental impairments (30 with cerebral palsy, 28 with global developmental delay, and 15 with epilepsy). Twenty five neonates died. The causes of neonatal seizure were hypoxic-ischemic encephalopathy (33.6%), metabolic
abnormalities (24%), intracranial hemorrhage (11.2%), development brain defects (4.8%), infections (4.8%), cerebral infarcts (4.0%), and miscellaneous (10.4%). The cause was unknown in 7.2% of the patients. Prematurity, low Apgar score at 5 minutes, seizure onset during first 24 hours of life, using more than one anticonvulsant, and presence of
acidosis were the apparent major determinants for adverse outcomes.

Discussion: Several factors may indicate worse outcome of neonatal seizure. Early recognition of infants at risk would be helpful for clinical management.

THE OUTCOME OF TERM INFANTS WITH NEONATAL SEIZURES IN ONE MEDICAL CENTER

Background and Objectives: To examine the outcome of neonatal seizures in a medical center in Taiwan.

Methods: This retrospective study enrolled newborns with neonatal seizures admitted between Jan 2003 to Dec 2009. Variables such as gestational age, type of delivery, birth body weight, APGAR score, type and etiology of seizures, EEG changes, AED efficacy were analyzed. The neurodevelopmental outcomes are classified as normal, developmental delay, cerebral palsy, epilepsy, and death.

Results: Among 18687 live babies, sixty-six neonates suffering from neonatal seizures were enrolled. Thirteen neonates were lost to follow-up one year after discharge. Six (9%) neonates died during admission. Of the other 47 patients, 26 (55%) infants had normal development, and 21 (45%) had neurologic impairment, including 11 (23%) with
cerebral palsy, 9 (19%) with developmental delay, 12 (25%) with epilepsy, and 3 (6%) reported dead during follow-up. Of 60 survivors, 16 infants were discharged without anti- epileptic drugs (AED), 35 with one AED, 5 with two AEDs, and 4 with more than three AEDs. Of the 12 patients with epilepsy, 7(58%) were well controlled and 5(42%) were
intractable. Of the 5 epileptic patients with treatment failure, 2 expired during follow-up.

Discussion: The mortality rate of neonatal seizures in our medical center in Taiwan was low, but the morbidity rate was high. The development of epilepsy was not uncommon and about 42% of the epileptic patients may have intractable epilepsy.

CLINICAL ANALYSIS OF JUVENILE MYOCLONIC EPILEPSY

Background: Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndrome. This syndrome is associated with multiple seizure types including generalized tonic-clonic seizure, absence seizures, and myoclonic jerks. It could easily be missed or misdiagnosed if the myoclonus is not elicited. This study is performed to define the clinical features and diagnostic strategies in pediatric patients of juvenile myoclonic seizure in a medical center.

Method: Retrospective review of patients with diagnosis of JME was conducted including the history, clinical course, and medical testings such as EEG & MRI.

Result: We reviewed carefully the medical records of nine patients who had been diagnosed with JME between 2004 and 2008. All of them but one have had a generalized tonic-clonic seizure (GTC)as the earliest symptom, but most of them have experienced myoclonic seizures before the medical visits.

The myoclonic seizures tend to occur in the early morning after wake-up. There were jerks of hands and arms more than legs. The mean age of onset is 11.9 years old (9 to 15) and the gender difference is 2:1 with male predominance.

The seizure types included myoclonic seizure in all patients and GTC in seven (77%) plus absence in two (22%). Three cases (33%) had been misdiagnosed to have another kind of epilepsy at first and prescribed with oxcarbazepine or clonazepam.

Series of EEG studies were done in all the patients. The interictal EEG showed a normal background with paroxysmal spikes or polyspike-and-waves at frontal or fronto- central area and bursts of secondary generalized 3.5 to 4 Hz spike-and-waves during awake and/or sleeping records. The spike-and-waves were also induced by photic stimulation and hyperventilation in six patients (66%). Magnetic resonance image (MRI) studies were performed in four patients and only one case revealed abnormal vascular lesion at frontal area.

All patients obtained good control under treatment with valproic acid. Six of them (66%) enjoyed seizure-free life and the others remained minimal myoclonic jerks. Two patients (22%) got a normal EEG results after treatment.

There were minor comorbidities included two with ADHD and two with tics. One case was suspected of Marfan syndrome with hypercholesterolemia.

Conclusion: The patients of JME could have had a generalized tonic-clonic seizure, but most of them had experienced myoclonic seizures. Confusion between JME and other epilepsy is not impossible. An electroencephalogram(EEG) had to show the typical abnormality called a fast (>=3Hz) spike-and-wave, with polyspike-and-wave pattern included. The history, such as the age at onset, myoclonic jerk in the early morning, might highlight certain problems. In JME, the seizure usually respond to average doses of valproic acid but not to carbamazeping or phenobarbital. Over half of patients may even become seizure-free.

CLINICAL MANIFESTATIONS OF CENTRAL NERVOUS SYSTEM GERMINOMA: A SINGLE INSTITUTION’S EXPERIENCE IN 10 YEARS

Hung-Ta Chen¹ , Ting-Rong Hsu^1,3 , Kai-Ping Chang¹ , Hsin-Hung Chen² , Muh-Lii Liang² , Tai-Tong Wong^2,3 , Tzu-Ying Yang¹ ,Chung-Hao Wang⁴ , Feng-Chi Chang⁵ , Yi-Wei Chen⁶ , Sang -Hue Yen⁶

Department of Pediatrics, Children’s Medical Center, Taipei Veterans General Hospital¹ ; Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital² ; National Yang Ming University School of Medicine³ , Taipei, Taiwan; Department of Pediatrics, Branch for Women and Children,Taipei City Hospital⁴ ; Department of Radiology, Taipei Veterans General Hospital⁵ ; Section of Radiation Oncology, Cancer Center, Taipei Veterans General Hospital⁶

Background: The central nervous system(CNS) germinoma is the most common type of germ cell tumor in pediatric brain tumors. The incidence in Asia is higher than Caucasian group. They are very sensitive to radiation and long term prognosis is very good if early diagnosis and treatment is provided. The study purpose is to reveal the clinical manifestations so that we can have a better view of it.

Methods: Pediatric and young adult patients diagnosed with CNS germinoma in Taipei Veteran General Hospital during 2001-2010 were enrolled. The diagnosis was based on radiologic or pathologic finding if surgery was performed. We retrospectively revealed the presenting clinical manifestations and their relationship with the locations in these
patients.

Results: There were 39 boys and 18 girls. Thirty patients had pathological diagnosis and the remaining 27 patients had radiological diagnosis. The most common initial symptoms were polyuria/polydipsia (24 patients), headache/dizziness (15 patients), and unsteady gait / limb weakness (12 patients). Five patients had initial presentation as short stature. The average duration from initial manifestation to diagnosis was 10.6 months.
The most common locations were suprasellar region (24 patients), followed by pineal region (12 patients) and basal ganglion region (11 patients). Ten patients had double midline tumor over the third ventricle floor and pineal region. The most common symptom of suprasellar tumor was diabetes insipidus, of pineal region tumor was headache/dizziness, of basal ganglion tumor was unsteady gait/limb weakness, and of double midline tumor was diabetes insipidus.

Discussion: The clinical symptoms are closely related to their locations. Some of the clinical manifestations may be very subtle and may take quite a long time before definite diagnosis. It is extremely important that pediatricians and general practitioners are familiar with the clinical manifestations of the CNS germinoma so that early diagnosis and early treatment can be provided.

IDENTIFICATION OF BIDIRECTIONAL GENE CONVERSION BETWEEN SMN1 AND SMN2 BY SIMULTANEOUS ANALYSIS OF SMN DOSAGE AND HYBRID GENES

Department of Pediatrics1 , Division of Pediatric Emergency² , Department of Emergency, Kaohsiung Medical University Hospital, Kaohsiung Medical University; School of Pharmacy, College of Pharmacy³ , Kaohsiung Medical University; Department of Laboratory Medicine4 , Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Institute of Clinical Medicine⁵ , Graduate Institute of Medicine⁶ , College of Medicine, Kaohsiung Medical University

Background and Objectives: Spinal muscular atrophy (SMA), a neurodegenerative disease characterized by programmed motor neuron death, is classified into three subtypes according to clinical severity: types I, II and III. The SMN1 gene is an SMA-determining gene being homozygously deleted in most patients, and SMN2 represents a highly homologous SMA-modifying gene. Although gene conversion from SMN1 to SMN2 has been proposed in previous studies, there has been little research on whether a reverse conversion, SMN2- to-SMN1, presents.

Methods: We applied capillary electrophoresis to quantify the SMN1 and SMN2 dosage in three Chinese population groups: 163 normal individuals, 94 SMA patients and 138 of their parents. Furthermore, we quantified exons 7 and 8 in SMN1 and SMN2 for all subjects to identify the hybrid SMN genes.

Results: Among the three groups, we found that the SMA patients carried the highest SMN2 copies, which was inversely correlated with disease severity among its three subtypes. Importantly, increased SMN1 was significantly associated with decreased SMN2 in the normal group. We also observed that parents of type I SMA patients had significantly fewer SMN2 copies than those of type II and III patients. The hybrid SMN genes were detected in two normal individuals and one SMA patient and her mother, bearing a similar sequence change of exons 7 and 8 in SMN1 and SMN2. These results imply that increased SMN2 copies in SMA patient group might be derived from SMN1-
to-SMN2 conversion, whereas the trend that normal individuals with higher SMN1 copies simultaneously carry fewer SMN2 copies suggested a reverse conversion, SMN2-to-SMN1.

Discussion: We have demonstrated the presence of bidirectional SMN gene-conversion events among three Chinese population groups. Noteworthily, the evidence of natural conversion events of SMN2-to-SMN1 could provide the basis of a potential therapy for SMA in the future.

NEUROLOGIC ASPECTS IN CHARGE SYNDROME WITH CHD7 GENE MUTATIONS

Background and Objectives: CHARGE syndrome is a multisystemic disorder composing of coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. About 60% to 65% of CHARGE syndrome presented with CHD7 mutations since Vissers et al found the genetic etiology in 2004. Variable phenotypes of CHARGE syndrome with CHD7 mutation have been reported in the world. however, rare cases are reported in Taiwan. With the broad clinical variability in this pleiotropic disorder, we try to summary neurologic aspects for quick approach of this rare syndrome.

Methods: We collected five children (3 boys, 2 girls) with genetically proved CHARGE syndrome from two medical centers in Taiwan. All cases performed developmental evaluation with Bayley II and brain imaging study. We discuss about neurologic manifestations, relevant multisystemic problems and imaging study.
Results: All our cases are consistent with common findings in CHARGE syndrome with the CHD7 mutation by Lalani et al. ( cardiovascular malformation, coloboma, and faical palsy asymmetry). Significant developmental delay were found in all cases. All cases presented with absent or hypoplasia of semicircular canal in high resolution temporal bone CT scan.

Conclusion: For approaching a child with global developmental delay, routine ophthalmologic consultation and hearing survey are necessary. For a child with developmental delay and significant hearing defects, we prefer temporal bone CT to brain MRI for more information. After reviewing the neurological aspects, we hope pediatric physicians will be better prepared to approach this rare syndrome.

ABNORMAL FINDINGS OF TC-99M HMPAO BRAIN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IN CHILDHOOD KLEINE-LEVIN SYNDROME

Background: Kleine-Levin syndrome (KLS) is a rare disorder characterized with periodic hypersomnia, sometimes accompanied by cognitive and behavior disturbances in adolescents. There were only few case reports of abnormal functional imaging measuring cerebral blood flow by single photon emission computed tomography (SPECT) performed in patients with KLS.

Methods: We retrospectively collect children diagnosed with KLS in the past 20 years. The demographic data, clinical manifestations and long-term outcome were described. The brain SPECT examinations, as well as EEG and brain imaging studies, were analyzed.

Result: Total 10 cases of childhood KLS, 8 boys and 2 girls, were reviewed. The median age of onset was 13 years (12 to 16 years). Hypersomnia was noted in 9 cases, and 1 had insomnia. The accompanied symptoms included cognitive changes (30%), eating disturbances (40%), hypersexuality (10%), and depressed mood (40%). The median duration of these episodes was 13 days (1 to 5 weeks), and the symptoms recurred every 3.3 months. Eight patients received medication, including methylphenidate, valproic acid or carbamazepine, but in vain. Two out of 8 patients had abnormal EEG finings. Brain imgaings were normal in 80% of patients. However, 80 % of patients had abnormal brain SPECT findings. There were hypoperfusion in thalamus (50%) , basal ganglia (10%), temporal lobe (50%), occipital lobe (10%), frontal lobe (10%), parietal lobe (10%), and cerebellum (40%).

Conclusion: Our studies demonstrated high incidence of abnormal brain SPECT findings in children with KLS.

NEUROLOGICAL COMPLICATIONS OF INFLUENZA INFECTION IN CHILDREN

Background and Objectives: To review the neurological manifestations and complications of influenza infection, when the pandemic influenza A started emerging after 2009.

Methods: We retrospectively reviewed the medical records of children (0-18 years old) who were admitted to National Cheng Kung University Hospital for influenza infection and concomitant neurological symptoms during August 2009 to February 2011. The clinical presentations, laboratory examinations, and images were analyzed.

Results: Twelve patients were included. The median of age was 5.6 years old (range: 2.0-16.5 years old). Eleven patients had influenza A H1N1 infection and 1 had influenza B. In these patients, 3 had seizures, 5 had disturbed consciousness, and 4 had both seizures and consciousness disturbance. Associated symptoms include visual hallucinations and dystonia-like movements. Image studies were arranged in 5 patients, which showed normal in 1, limbic encephalitis in 2, multifocal cortical and subcortical lesions in 1, and acute necrotizing encephalitis in 1. The prognosis was good generally.
However, the patient with necrotizing encephalitis became vegetative, and one patient with limbic encephalitis had refractory status epilepticus requiring long term anti-epileptic drugs.

Discussion: The neurological complications of influenza infection were diverse. The outcomes varied from good recovery to status epilepticus and vegetative states.

NEONATAL SUBGALEAL HEMORRHAGE: DIAGNOSIS AND PROGNOSIS

Objective: Subgaleal, also known as subaponeurotic hemorrhage, is a rare but potentially lethal condition found in newborns. It is caused by rupture of the emissary veins, which are connections between the dural sinuses and the scalp veins. Subgaleal hemorrhage can lead to severe hypovolemia, and up to one quarter of babies who require neonatal intensive care for this condition die. The prevalence of moderate-to-severe subgaleal hemorrhage at birth is approximately 1.5 per 10000 births. The risk factors include vacuum-assisted delivery, prolonged second stage of labour, fetal distress and macrosomia.

Methods: We reviewed charts retrospectively and focused on the early symptoms of
progressive subgaleal hemorrhage.

Result: Fifteen patients were reviewed in this study (between 1999-2011). All the
patients were late preterm or term babies (gestational age: 36-41 weeks). Birth weight
was around 2110-4510gm. Half of patients were delivered via vacuum assistance. Initial
hypotension was found in two-third patients, and metabolic acidosis in half. Ten patients
in this group needed blood transfusion. Five patients died despite of management.

Discussion: Subgaleal hemorrhage is most often associated with vacuum extraction and
forceps delivery, but it may also occur spontaneously. Optimizing the outcome for babies
with subgaleal hemorrhage requires early diagnosis.

CENTRAL DIABETES INSIPIDUS - A POOR PROGNOSTIC FACTOR IN CHILDREN WITH ACUTE BRAIN INSULT

Background and Objectives: Central diabetes insipidus occurs in patients suffering from overwhelming central nervous system injuries and is associated with brain death. The clinical picture of children with acquired central diabetes insipidus in a pediatric intensive care unit has seldom been reported.

Methods: We retrospectively reviewed cases between January 2000 and February 2008 in a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled.

Results: The etiologies were severe central nervous system infection (35.2%), hypoxic- ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72. 2%) of the 54 patients, diabetes insipidus was diagnosed during the first 2 days after the acute central nervous system injury, and 40 (74.0%) patients developed maximum
serum sodium concentrations of >160 mEg/L. In 16 children, central diabetes insipidus was combined with cerebral salt wasting syndrome. Overall mortality at 2 months after admission was 77.8%.

Discussion: Our results demonstrate that patients who develop central diabetes insipidus after an acute central nervous system injury have a high mortality. Development of diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of poor outcomes.

NEONATAL SEIZURES

Neonatal seizures represent a distinctive sign of neurological disorders in the neonatal period. Neonatal seizures have been suspected most often by witnessing unusual motor phenomena of the neonates. Its diagnosis has been made empirically and the efficacy of the treatment has been determined mainly by observation of motor symptoms. However, recent studies uncovered the several issues to be solved.
1) Diagnosis of neonatal seizures
The diagnosis of neonatal seizures must be based on ictal EEG findings. Recent studies revealed that clinical diagnosis of neonatal seizures is quite inaccurate. The majority of eizures by visual inspection lacks ictal EEG correlates, indicating that they are not of cortical origin. In contrast, ictal VTR-EEG studies show a frequent occurrence of subclinical seizures without any clinical symptoms.
2) Usefulness of conventional EEG
Conventional EEG is useful not only to diagnose neonatal seizures of cortical origin but also to presume underlying brain disorders. EEG shows repetitive, rhythmic, and stereotyped waves with some evolutional changes lasting for at least 10 seconds. The waveform of ictal paroxysms is usually of delta-theta-alpha range rather than spikes. Background EEG activities show suppression of activities in children with acute brain insult, altered waveform without suppression in those with remote symptomatic etiology, and normal waveform in those with idiopathic etiology.
3) Application of amplitude-integrated EEG
It is obvious that conventional EEG is the gold standard for confirmation of neonatal seizures. However, it is not easy to interpret conventional EEG of neonates for a majority of neonatologists or even for pediatric neurologists. Amplitude-integrated EEG has been widely used for the diagnosis and monitoring for neonatal seizures in Europe and USA. Amplitude-integrated EEG is easy to record and interpret even for persons without advanced interpretation skills. Application of amplitude-integrated EEG will be useful for rational diagnosis of and treatment for neonatal seizures.
4) Treatment based on EEG monitoring
The efficacy of antiepileptic treatment for neonatal seizures must be based on continuous EEG monitoring. Subclinical seizures remain quite often after clinical seizures are controlled by antiepileptic drugs. The accurate efficacy of antiepileptic drugs cannot be determined without continuous EEG monitoring. On the basis of our experience of continuous EEG monitoring, phenobarbital will be more effective than midazolam.

FUNCTIONAL BRAIN IMAGING IN NEONATES: RECENT ADVANCES

We have previously demonstrated, using positron emission tomography (PET) and 2-deoxy-2 (18 F) fluoro-D-glucose (FDG), that neonatal brain glucose metabolism is highest in primary sensory and motor cortex, cingulate cortex, medial temporal region, thalamus, brainstem and cerebellar vermis. Increases of glucose utilization are seen by 2-3 months in parietal, temporal and primary visual cortex, basal ganglia, and cerebellar hemispheres. Between 6 and 8 months, lateral and inferior portions of frontal cortex become more functionally active and, between 8 and 12 months, the dorsal and medial frontal regions also show increased activity. By approximately one year, the infant pattern of glucose utilization resembles qualitatively that of the adult. However, cortical metabolic rates of glucose utilization follow a nonlinear profile which is consistent with periods of synaptic exuberance and pruning in the human. These patterns of brain maturation provide some perspectives on developmental plasticity periods and timing of interventions.

Recently, we installed the Focus 220 animal microPET scanner (Concorde
Microsystems, Knoxville, TN) directly in our NICU for early diagnosis. Our preliminary studies documented the high spatial resolution (<2mm full-width-at-half-maximum) of this microPET. Abnormal patterns of glucose metabolism in thalamus and basal ganglia of neonates who had suffered from hypoxic-ischemic brain injury provided useful
predictions of later cerebral palsy.

We have also applied various¹¹ carbon-labeled PET ligands in neonates. For example,¹¹ C-PK11195 binds to the peripheral-type benzodiazepine receptors in activated microglia and provides a unique method to image neuroinflammation with PET. Studies using this ligand have found increased binding in white matter of newborns born to mothers with chorioamnionitis, suggesting activation of the inflammatory cascade in newborn brain as a result of maternal systemic infection (S. Kannan et al., 2009).

In studies using ¹¹ C-flumazenil in premature neonates, we have found patterns of binding which are dramatically different from those in full term babies, and also different from patterns of glucose metabolism. We find high ¹¹ C-flumazenil binding in basal ganglia, thalamus and brainstem of premature infants; this may indicate a transient expression of GABAA receptors in these structures during development.

Developmental trajectories of serotonin synthesis measured with PET and the tryptophan metabolism tracer alpha-[¹¹ C]methyl-L-tryptophan (AMT) indicate that serotonin synthesis capacity in non-autistic children is > 200% of adult values until about 5 years and then declined toward adult values. In autistic children, this 'surge' of serotonin synthesis capacity is markedly diminished. These data indicate a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children. Based on these findings, new approaches in the treatment of autism at an early age have been developed (D. Chugani et al., 1999).

NEONATAL BACTERIAL MENINGITIS

Bacterial meningitis is one of the most severe infections in neonatal period with high mortality and morbidity. In our patients, around one-seventh patients died and one-fourth had sequelae. Neonatal bacterial meningitis is usually transmitted via blood stream. Half to two-thirds of patients had concomitant culture-proved sepsis. There are several predisposing factors, e.g. prematurity, born by Cesarean section, congenital heart disease, premature rupture of membrane, etc.

The clinical presentations are usually nonspecific, i.e. hyper- or hypothermia, lethargy, irritability, anorexia, vomiting, respiratory distress, jaundice, hepatomegaly, etc. While seizure, bulging fontanel and neck stiffness are strongly related to meningitis.

Spinal tapping is the most important procedure to diagnose and prove bacterial meningitis. Neonates have higher WBC counts and protein levels, and lower glucose levels in CSF than older infants. Although CSF WBC count and protein concentration could be altered by a traumatic lumbar puncture, CSF sugar remains low in proved bacterial
meningitis.

Group B streptococcus and E. coli are the two major pathogens. Other hospital- acquired Gram-negative pathogens should be considered especially in late-onset neonatal infections. The empirical antibiotic choice needs to be adjusted according to the onset time and the epidemiology of each hospital. Supportive care is also very important, e.g. control
of seizure, blood and intracranial pressure, electrolytes balance.

Patients with acute neurologic complications have more adverse outcomes. Twenty to 60 percent of neonatal meningitis patients have neurologic sequelae. We found CSF protein more than 500 mg/dL, predisposing congenital heart diseases, acute hearing impairment and seizure are four poor prognostic factors. Thrombocytopenia, leucopenia,
low CSF glucose level, and use of inotropes have also been reported to be risk factors for poor outcome.

NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY: TREATMENT ADVANCES IN NEUROPROTECTION

Hypoxic-ischemic encephalopathy (HIE) accounts for 23% of the 4 million annual global neonatal deaths. In developed countries, the incidence of moderate of severe HIE has remained essentially unchanged over the past 20 years, at 1.5 to 2 per 1000 live births. Approximately 15 to 20 percent of these infants will die, and 20 to 25 percent of those who survive will be disabled. Physicians traditionally provided supportive care for these children with little expectation that their interventions would salvage brain tissue. However, this situation has changed over the past 5 years. Much evidence shows that moderate hypothermia for infants with mild or moderate HIE can substantially, although incompletely, reduces mortality and neurological disability. This therapy is increasingly being given to babies in special neurointensive care units where they can be monitored with continuous electrophysiological monitoring such as aEEG. These results also have greatly altered understanding of the theory of neuroprotection. Further research is on to discover adjuvant treatments that can augment the neuroprotective effects of hypothermia. Mitochondrial failure seems to be the key to secondary neuronal damage in HIE, and treatments that target the mitochondria might be useful. Inflammation enhances the effects of HIE, and anti-inflammatory drugs might turn out to be neuroprotective. Cell-based treatments are promising for their multiple neuroprotective effects and are being explored in preclinical models.

NEONATAL BRAIN IMAGING

Perinatal brain injury in survivors of premature birth has a unique predilection for periventricular cerebral white matter, while gray matters are commonly affected in the term brain. Paraventricular white-matter injury (PWMI) is the leading cause of brain injury in preterm infants and the predominant cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuses hypomyelination. Although the incidence of PVL is declining, focal or diffuse non-cystic injury becomes more and more common. Factors predisposing to PVL during prematurity include hypoxia, ischemia, and maternal-fetal infection. PWMI is mostly initiated by perturbations in cerebral blood flow accompanying anatomic and physiological immaturity of the vasculature. Injury to oligodendrocyte progenitors accompanying PWMI can disrupt the maturation of myelin-forming oligodendrocytes. Advanced PVL lesions progress either to cavitation or to a solid gliosis and may be accompanied by decrease in white matter volume, secondary cyst formation or adjacent ventricular enlargement. Recent cellular and molecular studies in experimental models and human tissue studies have revealed that there are fundamental differences in neuronal and glial function in the preterm and term brains as compared with later life. The developmental susceptibility of the brain at these stages is likely to be due to changes in the properties of multiple factors.

Use of early MR imaging may provide significant advantages over CT for identification of patients with CVA because (1) the early perfusion-weighted imaging (PWI) lesion estimates the brain region of acute hypoperfusion, whereas the acute diffusion- weighted imaging (DWI) lesion appears to correspond to the core of the early infarction;
(2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (or ischemic penumbra); and (3) in patients with a PWI/ DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion progression. Furthermore, decreased ADC values have also been reported in newborns with hypoxic-ischemic injury. The minimum ADC (<50% of control) was observed at ~2 days after injury, followed by an ADC increase.
(Pseudo) normalization was observed between day 7 and 8. Forbes et al. observed a decreased ADC (between 25-60% of control) in all cortical injuries during the first 10 days, and both decreased and increased ADCs in thalamic injuries.
Reference:

1. Back, Stephen A. MD, PhD; Riddle, Art BS; McClure, Melissa M. PhD Stroke volume 38 (2, Part 2) Supplement, February 2007, pp 724-730

NEUROSURGICAL DISEASES IN NEONATES

新生兒的神經外科疾病患包括一些中區神經系的先天畸形(例如:腦膜膨出 、腦膨出、腰薦椎脊膜脊髓膨出合併脊髓牽扯等）與一些罕見的先天腦血管病變或腫瘤。較常見的疾患則包括早產兒或新生兒腦出血合併或未合併水腦症的發生。此外是一些與生產相關的顱內、顱外出血。

有的疾患需要手術來處理，有的時候保守療法就可以。需要手術處理者，有的是會危及生命安全的急症，有的則適合選擇適當的手術時機來進行。

本報告除了介與新生兒時期相關的神經外科疾患之外，也將說明手術之適應症與時機。

CASE REPORT OF AICARDI SYNDROME

Background and Highlight: Aicardi syndrome represents a complex disorder that affects many systems and is typically associated with agenesis of the corpus callosum. Patients are almost all female, suggesting a genetic abnormality of the X chromosome (it may be lethal in males during fetal life). Seizures become evident during the 1st to a few months and are typically resistant to anticonvulsants. An electroencephalogram shows independent activity recorded from both hemispheres as a result of the absent corpus callosum. Abnormalities of the retina, including circumscribed pits or lacunae and coloboma of the optic disc, are the most characteristic findings of Aicardi syndrome.

Case Report: We report a 6-month-old girl who had infantile spasms diagnosed when she was one-month old. Seizure attacks with blinking of right eye and flexion of left limbs were noted at about 20 days of age. Nodding and flexion of limbs were noted at about 1 month of age, and she was brought to one medical center where infantile spasms
were diagnoised. Brain MRI showed agenesis of corpus callosum. Valproic acid, clonzaepam, vigabatrin, vitamin B6, and ACTH were tried. Regression in head control developed. Anticonvulsants were discontinued by her parents. They also omitted ACTH for two doses. Traditional herb medicine was tried. Persistent irritable crying, irregular movements of limbs, and post-prandail vomiting 1~2 times per day had been noted for 3 days before she was admitted to another medical center. She had no diarrhea, fever, or URI symptoms then. Convulsion of left leg and blinking of eyes were noted. Diazepam was occasionally given intravenously. She has developed into intractable epilepsy and severe sychomotor retardation up to now.

Laboratory Data: EEG showed atypical hypsarrythmia with multifocal epileptiform discharges; there were multiple independent epileptiform activities over left occipital area only, and some multifocal foci over right parieto-occipital, and bilateral fronto-temporal areas; meanwhile, diffuse cortical dysfunction was also noted. Brain MRI showed
agenesis of corpus callosum and cortical dysplasia over bilateral frontal & temporal areas.
Optic disc dysplasia and multiple retinal-choroidal lacunae were noted by ophthalmological consultation. Moreover, brain SPECT showed hypoperfusion over left frontal, temporal, parieto-occipital, and right temporal areas. Aicardi syndrome was then diagnosed. But chromosomal genetic study showed normal female karyotype.

Discussion: (1) In light of this patient, a newborn or young female infant with early- onset infantile spasms should be first considered as Aicardi syndrome. (2) It is important that brain malformation may consist of agenesis of corpus callosum and other cortical dysplsia, and fundus retinal examination may provide further evaluation and information
for clinical diagnosis. (3) The genetic study for Aicardi syndrome is still under development.

GABAPENTIN AS AN EFFECTIVE TREATMENT FOR POST - CRANIOTOMY VOMITING IN PATIENTS WITH A POSTERIOR FOSSA TUMOR

Background and Highlight: Gabapentin is well understood for pain control and antiepileptic effect. The antiemetic effect of gabapentin is poorly investigated. We report that gabapentin is effective for refractory vomiting after craniotomy in two children with medulloblastoma within the fourth ventricle.

Case Report: The two pediatric patients, an eleven-year-old girl and a five-year-old boy, received nearly total excision of the tumor via craniotomy. Both of them suffered from refractory post-operative nausea and vomiting. They had been treated with multiple traditional antiemetic drugs without benefits. Their nausea and vomiting got improved
from one to two episodes of vomiting per day to complete resolution of symptoms after gabapentin prescription.

Discussion: Our report implies that gabapentin, a novel and emerging antiemetic therapeutic intervention, can be considered in patients who suffer from refractory nausea and vomiting after craniotomy.

EFFECT OF MOZART K.448 ON ALPHA POWER OF EEG

Background and Objectives: Music has been used to reduce anxiety and relax our mind. However, there were few scientific evidences which showed central nervous system effect by listening to music. Mozart effect was initially described by Rauscher et al. They reported that students scored nine points higher on spatial tasks after listening to Mozart’s Sonata for two pianos in D major, K.448 (Mozart K.448) for 10 minutes when compared with the same time of silence, or relaxation. EEG alpha power is inversely related to neural electrical activity. We investigate the effect of Mozart K.448 on EEG alpha power.

Methods: Twelve college students (aged 19-22 years) were enrolled in this study.
Subjects received EEG examinations before (8 minutes), during (8 minutes) and after (8 minutes) listening to Mozart K.448. Each participant maintained the same state of wakefulness throughout the recording period. Alpha power of EEG was compared before, during, and after music.

Results: There were five males and seven females recruited for this study. During listening to Mozart K.448, there were significant reductions of alpha power in all subjects by average 15.07±10.89% in F3-C3, 14.43±9.77% in F4-C4, 10.54±11.84% in C3-T3, 12.25±11.57% in C4-T4, 18.18±13.07% in T3-O1, 17.16±14.73% in T4-O2, 16.90±13.
42% in O1-C3, 17.10±15.68% in O2-C4 found by EEG recordings. However, there was no significant change in alpha power after music exposure when compared to before music stage. The results also revealed significantly decreased beta power in T4-O2 and O2-C4 during music exposure, while significant reductions in theta power were found in T3-O1, O1-C3, T4-O2 and O2-C4 during music exposure.

Discussion: The decrease in alpha power during music listening suggests that people have consistent mental state and more relaxation. Decreased alpha power is often associated with an increase in cognitive functioning and may reflect enhanced semantic memory performance and object recognition.

POST-STROKE SEIZURE AND EPILEPSY IN CHILDHOOD ARTERIAL ISCHEMIC STROKE

Background and Objectives: Acute ischemic stroke is increasingly recognized as an important cause of mortality and morbidity in pediatric population. The occurrence of seizure and epilepsy after acute ischemic stroke is less studied in children. Therefore, the aim of this study was to assess the type and severity of seizure after acute ischemic stroke and its effects on the outcome of stroke.

Methods: In this retrospective study, we collected children aged from 1month to 18 years admitted to our hospital due to first episodes of acute ischemic stroke in the past 14 years. The early, and late seizure outcomes of these patients were oralnated.

Results: Thirty-seven (36%) out of 102 children with arterial ischemic stroke had post- stroke seizures. In thirty-three out of these patient, post-stroke seizures were new onset seizure, with early seizures in 30 and late seizures in three. Heart disease was the most common etiology of stroke in both groups of early (28%) and late (67%) post-stroke
seizures. Post-stroke epilepsy developed in 15 children(41%), including 12 with early post-stroke seizure (12/30) and 3 with late post-stroke seizure(3/3). The post-stroke epilepsy mostly occurred within 1 years (64%). However, 31% developed after 2 years.

Discussion: Post-stroke seizures and epilepsies in childhood arterial ischemic stroke are very common. Most of them are associated with heart diseases. The post-stroke epilepsy often occurs within one year after stroke.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME IN CHILDREN

Background and Highlight: Posterior reversible encephalopathy syndrome (PRES) is a kind of hypertensive encephalopathy with clinical characters of headaches, altered mental status, seizures and visual impairment. The cardinal image feature is focal, reversible, vasogenic edema of posterior occipital and parietal lobes of brain. PRES is associated with several clinical conditions. In this study, we identify the clinical condition, neurologic presentation, and magnetic resonance image (MRI) characters in 4 children with PRES.

Methods: In this study, we retrospectively review 4 children having PRES during 2009- 2010 in Taipei Veterans General Hospital. We reviewed in detail the clinical conditions, presenting symptoms, risk factors and brain imaging findings in these 4 patients.

Results: These four patients have different underlying diseases including brain tumor, nephrotic syndrome, systemic lupus erythematosus and aplastic anemia. Hypertension, nausea and vomiting were the initial presentation of all patients. Visual impairment occurred in 3 patients and two of them had fully recovered. Seizure developed in 3 cases, two with generalized tonic-clonic seizure (GTCs) and one with secondary generalized GTCs. The mean systolic blood pressure was 158 mmHg (149-166 mmHg) and the mean diastolic blood pressure was 108 mmHg (78-125 mmHg). Two developed PRES during methylprednisolone pulse therapy, one while receiving cytotoxic agents (Cisplatin, Vinblastin, Etoposide and Bleomycin), and one while receiving methylprednisolone and cyclosporine. The brain lesions were found to locate in occipital, parietal and frontal areas on brain MRI. The lesions involved not only white matter but also cortical and subcortical area. Three of them had vasogenic lesion with hypointense signal in diffuse weighted image (DWI) and hyperintense signal in apparent diffusion coefficient (ADC) image at occipital, parietal, frontal and cerebellar areas. One had ischemic lesion with hyperintense signal in DWI and hypointense signal in ADC image at bilateral occipital and parietal areas.

Discussion: PRES occurs mostly in autoimmune disease. Hypertension occurs with the appearance of neurologic deficits. Steroid is probably the most common risk factor contributing the hypertension. PRES involves not only in posterior portion of brain, but also in the frontal and other areas of brain. Either vasogenic or ischemic process may
occur in PRES.

ISCHEMIC SPINAL CORD INFARCTION IN A 14-YEAR-OLD BOY WITH LUMBAR SCHEUERMANN’S DISEASE: A CASE REPORT

Background and Highlight: Spinal cord infarction is a rare condition with difficult diagnosis due to small transverse area. The risk factors for obstruction of blood flow include cardiovascular compromise or malformation, iatrogenic or traumatic vascular injury, cerebellar herniation, thromotic or embolic disease, infection and vasculitis. We report a boy who suffered from acute paraplegia after performing squat jump and lumbar Scheuermann’s disease was diagnosed by the spinal MRI. The possible mechanism of the spinal cord infarction with Scheuermann’s disease will be discussed.

Case Report: A 14-year-old athletic boy with episodic low back pain history suffered from acute paraplegia after squat jump without traumatic event. The physical exam revealed decreased muscle power of bilateral lower legs combined with absence of temperature and pain sensation below the level of T12 while vibration and proprioception
were intact. The T2WI of spinal MRI discloses wedge shaped enhancement of anterior spinal cord in the level of T12. Besides, the spinal MRI also revealed degeneration of lumbar spine with spur formation, irregular endplate and intraosseous disc herniation which is compatible with the diagnosis of lumbar Scheuermann’s disease. The boy has
no risk factor of cardiovascular disease, infection, or vasculitis. The lab data for coagulopathy was normal.

Discussion: Scheuermann’s also known as juvenile kyphosis, is characterized by wedging deformity of vertebrae. The lumbar type Scheuermann’s disease the normal square shape has irregular endplate with disc bulging into the vertebrae (Schmorl’s nodes) in spite of maintaining. It occurs mostly in teenage athletes who perform strenuous physical activity. Valsava maneuver may extrude the nucleus pulposus material through the vertebral endplate into the vertebral body. The fibrocartilaginous material within the nucleus pulposus acts as the embolus which drains into the spinal circulation by retrograde flow via arteriovenous anastomosis. Eventually, it blocks the anterior spinal artery and leads to spinal cord infarction. Pathologic biopsy is the only way to prove this hypothesis.

DELAYED-ONSET INVOLUNTARY MOVEMENTS FOLLOWING CARBON MONOXIDE POISONING: A CASE REPORT

Background: Delayed-onset of neuro-psychiatric symptoms after apparent recovery from acute carbon monoxide (CO) intoxication has been described 3 to 40 days after exposure in about 10% to 30% of victims. The clinical manifestations of delayed-onset of neuro- psychiatric sequelae are variable, such as cognitive decline, apraxia, agnosia, personality changes, emotional lability, amnestic syndrome, parkinsonism, incontinence, dementia, and psychosis. We report a patient with delayed-onset involuntary movements following carbon monoxide poisoning. The brain magnetic resonance imaging (MRI) showed bilateral globus pallidus hyperintense lesions on T2WI, highlighting the clinical and image correlation.

Case Report: An 8-year-old boy was found unconscious and unresponsive in the bathroom during taking shower. The patient was put on oxygen non-rebreathing mask during transportation. Upon arriving at emergency department, the patient’s consciousness improved a bit. However, the fraction of carboxyhemoglobin (FCOHb) level was 39%,
hyperbaric oxygen therapy (HBOT) was performed. After hospitalization for 3 days, the patient’s consciousness was clear and vital signs were stable on discharge. However, easy falling down, poor hand-writing, and limb involuntary movements were noted at school four days after discharge. He couldn’t stand and walk well due to progressive involuntary movements. Besides, frequent tongue protrusion, easy choking, and slurred speech were also noted. The brain magnetic resonance imaging (MRI) showed bilateral globus pallidus hyperintense lesions on T2WI. These conditions were improving in the next month.
However, impaired attention and slow mental processing were still complained.

Discussion: No clinical or laboratory results can predict which patients are at risk for delayed-onset of neuro-psychiatric symptoms following carbon monoxide poisoning. The central nervous system (CNS) lesions most commonly involved include the globus pallidus and the deep white matter. The predilection for the globus pallidus is unclear
but may be related to the hypotensive effects of carbon monoxide poisoning in the watershed territory of the arterial supply or to the characteristics of the globus pallidus which is iron-rich. The adverse effects of carbon monoxide on vascular endothelium, post-ischemic reperfusion injury, and free radical-mediated lipid peroxygenation may play
a role in the pathophysiology. The involuntary movements highlight the suspicious lesions in the basal ganglia, specially globus pallidus.

A CASE REPORT OF ENCEPHALITIS LETHARGICA

Background and Highlight: Encephalitis lethargica (EL) is defined as an acute or subacute inflammatory encephalopathy that predominantly affected the basal ganglia and midbrain resulting in extrapyramidal symptoms, behavioral disorders and sleep disturbance. Abnormal movements is usually first symptom of EL in young children. It is important to exclude other possible etiologies of acute encephalopathy before the diagnosis of EL is made. Early aggressive immuno-modulating therapies may lead to more rapid recovery and reduce morbidity.

Case Report: A 4-year-old boy presented with acute left hemiballismus and tongue thrusting 7 days after an upper respiratory tract infection. One day after admission, the involuntary movements involved the entire body. He also developed lethargy, unsteady gait, visual hallucination and intermittent rotating of eyeballs, like oculogyric crises. On
day 3, the patient receives risperidone (0.5mg qd) and intravenous immunoglobulin treatment (2g/kg), which resulted in gradual improvement of his symptoms. At the time of discharge, the patient can walk without assistance. Followed up for 10 months after the onset of the illness he had complete recovery, except some choreiform limb movements with medication required .

Laboratory Data: The cerebrospinal fluid analysis revealed lymphocytic pleocytosis and protein 43mg/dl. Extensive infectious work ups yielded negative findings. His EEG was normal and brain MRI showed T2-weighted changes in the bilateral lentiform nucleus.

Discussion: Our patient was most likely to consist with dyskinetic form of EL because of had prominent dyskinetic movements followed by lethargy and visual hallucinations.
More than 60% of EL had normal brain MRI in acute phase, but our case showed abnormalities in the lentiform nucleus. Recent studies reported most of dyskinetic form of pediatric EL had positive NMDA receptor antibody, and the titers of antibody is supposed correlated with clinical outcome. However, NMDA receptor antibody is not available here. There are no established recommendations for the treatment of EL. Our patient had favorable outcome after early use of IVIG with dopaminergic agent, but additional study is warranted in this area.

ACUTE NECROTIZING ENCEPHALOPATHY WITH INFLUENZA A INFECTION: A CASE REPORT

Background and Highlight: Acute necrotizing encephalopathy (ANE) is a rare acute encephalopathy occurring after febrile illness. Typical presentations include hyperpyrexia followed by rapidly progressive coma and convulsions with high mortality rate or severe neurological sequelae. The characteristic brain magnetic resonance imaging findings are symmetric involvement of the bilateral thalami, brainstem, cerebral periventricular white matter or the cerebellum.

Case Report: We report a 3-year-10-month-old previously healthy girl who displayed typical manifestations of ANE associated with H1N1 influenza infection proved by polymerase chain reaction. She suffered from fever followed by convulsions and deterioration of consciousness. The clinical course was complicated with shock, anuria and massive bleeding tendency. Brain and magnetic resonance imaging showed bilateral symmetrical lesions of the thalami, cerebellar hemispheres, brainstem, globus pallidum, and frontal central parenchyma suggestive of ANE. Antiviral agents including oral Tamilfu and intravenous Rapiacta(Peramivir) were prescribed. She was also treated with intravenous immunoglobulin (1g/kg/day 2 days) and methylprednisolone pulse therapy for 1 day. However, devastating clinical course couldn’t be restored under aggressive treatment. Acute onset of massive intracranial hemorrhage happened 2 weeks later with rapid progress of brain death and eventual death.

Discussion: Our patient presented atypical manifestations associated with H1N1 infection.
Physicians should be aware that ANE may represent a cause of altered mental status in children with H1N1 infection. Although the pathogenesis of ANE remains unclear, the cytokine storms have been implicated for the devastating outcome.

RECURRENT ASEPTIC MENINGITIS AS AN INITIAL PRESENTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS

Background and Highlight: Systemic lupus erythematosus (SLE) is characterized by a wide variety of clinical and serological manifestations with relapsing and remitting course. Central nervous system involvement most commonly manifested as cerebritis with seizures, cranial nerve deficits, or psychiatric disturbances, occurs in 37-82% of patients with SLE. However, aseptic meningitis, though infrequent, had been reported as the initial presentation of SLE.

Case Report: A 16-year-old female who visited to the emergency department with the complaints of severe headache, nausea and fever for 6 days. Her past medical history included major depression and episodes of aseptic meningitis since 2 years ago. The physical and neurological examinations were unremarkable for any skin lesion or focal
neurologic sign. Cerebrospinal fluid (CSF) survey for pyretic illness revealed pleocytosis, and aseptic meningitis was impressed initially. After the immunological studies confirmed SLE, corticosteroid therapy was started with symptom imrpovement. She received regular follow-up in outpatient clinic without neurologic deficits within 2 years after onset of symptoms.

Laboratory Data: Brain computed tomography was unremarkable. CSF survey showed clear appearance with a normal opening pressure except pleocytosis up to 26/ul, and glucose of 45 mg/dL (simultaneous serum glucose of 108mg/dL). The protein pandy test was positive in CSF. The diffential count of the CSF WBC was 17 % lymphocytes, 10% monocytes, and 73% neutrophil. Testing the CSF for bacteria, and viral agents (CSF PCR for herpes simplex, varciella zoster, and enterovirus) were all negative. Hematologic examination showed pancytopenia (WBC: 2230/ul,Hb:11.1g/dl, and platelet: 122000/ul ). The ANA, anti-dsDNA, anti-ENA (SSA,SSB) were all positive. The complement C3/ C4 levels were within normal limits. The serological panel was negative for anti- cardiolipin IgG.

Discussion: Many different neurological conditions are associated with SLE. The most common manifestations are headaches, seizures, cerebrovascular accidents and aseptic meningitis. The cerebrovascular accidents can be due to arteriovascular disease or thrombus formation, particularly in those with anti-phospholipid antibodies. We suggest that recurrent a septic meningitis without significant pathogens proved should be considered in the differential diagnosis of neuropsychiatric SLE syndromes.

BRAIN PERFUSION STUDY OF HYPOGLYCEMIC HEMIPARESIS IN A PATIENT WITH INSULIN-DEPENDENT DIABETES MELLITUS

Background and Highlight: The common sign of hypoglycemia consists of tachycardia, diaphoresis and disturbances of consciousness. There were several case reports describing patients with insulin-dependent diabetes mellitus presented with transient hemiparesis associated with hypoglycemia. The angiography was normal. Full recovery of neurological dysfunction occurred after correction of hypoglycemia. Hypoglycemic hemiparesis is rarely described in children and adolescents. We reported a child with insulin dependent diabetes mellitus presented with hypoglycemic hemiparesis and cerebral hypoperfusion noted by brain perfusion study.

Case Report: A 6-year-old female, with insulin-dependent diabetes mellitus diagnosed for two years, presented with abrupt onset of right limbs weakness and dysarthria. There were no loss of consciousness or seizure-like-episode. Glucose level detected during the attack was 40mg/dl. Parenteral glucose supplement was performed. Her neurological
dysfunction fully recovered within 24 hours. Enhanced brain computed tomography and brain MRI were arranged one hour and nine hours after the attack, respectively.

Laboratory Data: Enhanced brain CT showed no cerebral vascular stenosis, dissection, aneurysm or space-occupying lesion, however, decrease in cerebral blood flow in the left temporo-occipital lobe was found by CT perfusion study. Brain MRI, performed eight hour later, revealed no hemorrhagic or ischemic lesion. One day later,
electroencephalography revealed no epileptiform discharge.

Discussion: It is postulated the pathogenetic theory of “hypoglycemic hemiparesis” involves selective neuronal vulnerability, regional blood flow disturbances or underlying ischemic disease. The image findings of our case could be an evidence supporting the theory of regional blood flow disturbances during hypoglycemic state.

A TERM INFANT WITH ISOLATED SULFITE OXIDASE DEFICIENCY

Background: Isolated sulfite oxidase deficiency (ISOD) is a rare autosomal recessive inherited disorder which is easily misdiagnosed as hypoxic ischemic encephalopathy (HIE).

Case Report: We described one female term infant with ISOD born to healthy non- consanguineous parents. Her elder sister also had intractable seizure, and brain MRI at 1 month of age demonstrated multicystic encephalomalacia which was erroneously labeled as HIE with a low recurrent risk. The patient presented with seizures at first day
of life. Intractable seizure, cerebral palsy, and psychomotor retardation were observed later. Serial changes of brain MRI showed diffuse edema with posterior predominance, then progressive multicystic encephalomalacia and brain atrophy with thalami spared.
Brain perfusion scan revealed absent uptake in the cerebellum and bilateral frontal lobes.

Laboratory Data: A diagnosis of ISOD was established by low plasma homocystine and SUOX exon 6 homozygous mutation(c.1200C>G (p.Y400X).

Discussion: ISOD is also an important differential diagnosis, especially in infants without obvious eonatalasphyxia. The characteristic neuroimages of ISOD, such as cerebral edema with posterior predominance and progressive brain destruction with thalami spared, are different from HIE, and early diagnosis may be helpful to genetic counseling for
further pregnancies.

TWO CASES OF HIRAYAMA’S DISEASE

Background and Highlight: Hirayama et al. reported 12 cases of juvenile unilateral muscle atrophy of an upper limb in 1959. They emphasized that this was a new clinical entity because its clinical presentations were different from degenerative and progressive types of motor neuron disease.

Cases Report: We report two cases, who were 16-year-old(Case 1) and 14-year-and- 9-month-old (Case 2) previously healthy boys, without neck or hand injury before onset of symptoms. No history of poliomyelitis was presented. None of our patients had any family history of neuromuscular disease. Case 1 presented painful sensation and spasms on exertion of right index finger for months. Physical examination revealed normal deep tendon reflex but atrophy of hypothenar muscles. Case 2 developed numbness and weakness of right thumb for 2 months. Physical examination showed mild knocking pain over right side of neck with atrophy of extensor digitorum communis.

Laboratory Data and MRI Findings: Their serum creatine kinase and other routine laboratory tests were within normal limit. Nerve conduction velocity studies revealed reduced amplitude of the compound muscle action potential of the ulnar nerve. In Case 1, the electromyography showed spontaneous activities in the right first dorsa interosseous and abductor pollicis brevis. Both of them, T1-weighted post gadolinium showed the anterior subarachnoid space is completely effaced when neck is hyperflexion the spinal cord is compressed, and posterior dura is shifted ventrally more on the righ side at the lower cervical segments.

Discussion: After reviewing of the literature of juvenile muscular atrophy of distal upper extremity, the presentations of our two patients are consistent with most series. They both are male, right hand involved and disease onset is in adolescence. In those series, the duration of progression varies widely, ranging from 16.8 to 73.2 months. Hirayama disease ceased to progress within 5 years.

LESCH-NYHAN SYNDROME ASSOCIATED WITH LARYNGOMALACIA: A CASE REPORT

Background and Highlight: Lesch-Nyhan syndrome(LNS) is a rare X-linked recessive genetic disorder of purine salvage caused by a complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT) activity and presented with hyperuricemia, chorea and self-mutilation. Laryngomalacia characterized by inspiratory collapse of lax supraglottic tissues into the laryngeal inlet. It is may on occasion cause obstruction of the airway and require intervention. We report a case of LNS associated with laryngomalacia.

Case Report: We report a 1-year-and-10-month-old boy who had recurrent respiratory failure and difficulty in extubation since birth. He developed laryngomalacia type A at the age of 6 months. At the age of 5 months, he was diagnosed of renal tubular acidosis and nephrolithiasis. He was also noted to have development delay, persistent chorea when awake, and compulsive self-mutilation such as biting fingers, lips and buccal mucosa.
There’s no abnormal finding on brain MRI. Physical examination revealed bed-ridden with mental retardation. Respiratory distress with recurrent stridor was observed over the chest.

Laboratory Data: Mild elevated serum uric acid level up to 7.6mg/dL on serial tests.
Spot urine uric acid to creatine ratio equal to 116/50 (> 2.0). The HPRT cDNA, amplified from total RNA of the patient’s peripheral blood by reverse-transcription PCR study, showed the absence of exon 6. Family study revealed that his mother was a heterozygous carrier.

Discussion: Diagnosis of LNS has frequently been delayed until self-mutilation was evident.
A high serum uric acid concentration up to 18 mg/dL is usually the biochemical finding that prompts special testing for the specific diagnosis. However, infants with LNS may have borderline serum uric acid levels due to increased renal clearance of uric acid, and it is suggested the urinary uric acid/creatinine ratio >2 can be employed as a screening test for inherited disorders of purine metabolism, based on the age of the patient. Our case with typical symptoms of LNS was genetically diagnosed. The molecular diagnosis suggests HPRT encoded on the long arm of the X chromosome at
Xq26. However, there’s high degree of heterogeneity in type and location within the gene: deletions, insertions, duplications, and point mutations.

Laryngomalacia represents a benign self-limiting condition in 90% of patients, disappearing by the age of two to five years. We report laryngomalacia may be another symptom associated with LNS.

INTRANUCLEAR RODS MYOPATHY WITH AUTONOMIC DYSFUNCTION

Background: Intranuclear rods myopathy (IRM) is a subtype of actinopathy, defined as actin filament aggregate myopathy caused by ACTA1 mutation, presented as respiratory distress, general weakness since birth. In addition to muscle phenotype, autonomic dysfunction was rarely detected in the patients with IRM.

Case Report: We herein report a 1-year-old female infant with IRM and autonomic dysregulation. Severe hypotonia with respiratory failure were noticed since birth and nemaline rods within myonuclei were found in biopsied muscle by histochemistry and electromicroscope analyses. During the infancy, diaphoresis, facial flushing, intermittent
tachycardia, bradycardia and hypertension with the precipitating factors of feeding, defecation, and urination were observed.

Conclusion: Our finding further broadens the clinical spectrum of IRM and implies the possible role of alpha-actin in autonomic nerve system.

A NEONATAL ENCEPHALOMYOPATHY ATTRIBUTED TO MITOCHONDRIAL DEPLETION SYNDROME: A RATIONAL APPROACH

Background and Objectives: To describe a newborn who presented with neonatal encephalomyopahty and renal tubulopathy. To highlight a mitochondrial depletion syndrome can cause newborn-onset encephalopahty, myopathy, seizures, and renal tubulopathy.

Patients and Methods: The female newborn was myopathic after birth and subsequently developed feeding difficulties, ophthalmoplegia, ptosis, encephalopathy, and seizures. She became ventilator-dependent after sudden apnea. Detailed clinical examinations: brain magnetic resonance imaging, morphological analysis of a muscle biopsy, characterization
of mitochondrial DNA copy number. The myopathy was without ragged red fibers in the muscle biopsy. The electroencephalogram was normal initially but subsequently showed burst suppression pattern. The mitochondrial copy number in skeletal muscle was 2% of normal.

Results and Discussions: Physicians should be aware of mitochondrial depletion syndrome related encephalomyopathy in newborns or early childhood-onset encephalopathy combined with myopathy and renal tubulopathy, because it has important implications for management, treatment, and genetic counseling.

A CASE REPORT OF X-LINKED FAMILIAL CONGENITAL NYSTAGMUS SYNDROME

Background and Highlight: Congenital nystagmus (CN) is an ocular motor disorder of unknown etiology that presents at birth or early infancy and is clinically characterized by involuntary oscillations of the eyes. The incidence of all forms of infantile nystagmus is estimated to be 1 in 5,000 newborns. X-linked, autosomal dominant, and autosomal recessive modes of inheritance have been reported, but X-linked inheritance is probably the most common.

Case Report: We report a male infant presented with jerky horizontal nystagmus since birth. His birth history was smooth, and no perinatal insult was noted, except for neonatal hyperbilirubinemia. The ophthalmologist was consulted and no obvious anomaly was noted. Besides, we noted his two uncles and grandmother have similar nystagmus. Then
a strong family history of X-linked congenital nystagmus in this Taiwanese family, including 10 individuals with CN (2 females and 8 males), over 3 generations, and 14 healthy relatives were revealed.

Laboratory Data: Initially we found hyperblirubinemia (total bilirubin: 18mg/dl; direct bilirubin: 0.4mg/dl). All the other parameters, including CBC/DC, AST, ALT, Coomb’s test and newborn screening were negative findings. Abdominal and brain ultrasonography were both within normal limit.

Discussion: There are three common forms of nystagmus in childhood, including congenital nystagmus (CN), fusion maldevelopment nystagmus syndrome, and spasmus nutans syndrome. X-linked CN is mainly caused by mutation of FRMD7 gene. The patients with X-linked CN usually have normal color vision and relatively normal visual acuity (typically better than 6/12). Besides, genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.

A CASE REPORT OF PELIZAEUS -MERZBACHER DISEASE

Background: Pelizaeus–Merzbacher diseaseis (PMD) is a rare disorder of central nervous system myelination. Mutations in proteolipid protein 1 (PLP1) on the long arm of the X-chromosome (Xq22) account for 80% of this disease. Coordination, motor abilities, and intellectual function are delayed to variable extents, primarily depending on the precise nature of the causative mutation. Several types are recognized, including infantile type and adult type. In chronic infantile type, it is slowly progressive and the early symptoms include rotary movements of the head and eyes, usually followed by spasticity of the legs and arms, cerebellar ataxia, dementia, and parkinsonian tremor.

Case Report: We describe a 33-year-old female who visited our clinic for genetic counseling due to positive family history of suspicious neuromuscular disorder. Both her brothers and uncle were the victims of development delay since infancy and have never been able to walk independently. They all displayed infant-onset spastic quadriplegia and
hyperreflexia. In the later stage, tremor and involuntary movement of head were getting remarkable. However, the disease course did not show obvious regression. Due to cerebral palsy (CP)-like features and possible X-linked inheritance, brain magnetic resonance imaging (MRI) and mutation analysis of PLP1 were performed on affected
brothers.

Laboratory Data: MRI showed diffuse leukodystrophy. A novel point mutation in PLP1, c.88 G>C was identified in these two affected brothers. This mutation was also found in asymptomatic grandmother, mother, sisters and the symptomatic uncle.
Another unaffected uncle did not harbor this mutation.

Discussion: PMD shows a CP-like clinical phenotype. Unless there is a family history consistent with sex-linked inheritance, the condition is often misdiagnosed as cerebral palsy. Therefore, in terms of a sporadic CP, we should always keep the disease in mind.

A CASE REPORT OF JOUBERT SYNDROME

Background and Highlight: Joubert syndrome (JS) was originally described in 1968 in four siblings with agenesis of the cerebellar vermis presenting episodic hyperpnea, abnormal eye movements, ataxia and intellectual disability. Several years later, a pathognomonic midbrain-hindbrain malformation, the “molar tooth sign”, was detected first in JS.

Case Report: We report a 1-year-old-and-1-month-old male infant who has a smooth natural delivery history without perinatal insult. He was a fullterm newborn and bodyweight, length and head circumference were within normal percentile. Since he was 6-month-and-15-day-old, he developed poor eye contact and hypotonia. He still could not roll over near the age of 7 months.
When he was 1-year-and-1-month-old, horizontal nystagmus and no crawling were noted. Developmental assessment revealed delay in gross motor, language and social skills.

MRI Finding: A combination of midline cerebellar vermis hypoplasia, deepened interpeduncular fossa, and thick, elongated superior cerebellar peduncles gives to the axial view of the midbrain an appearance of a molar tooth, known as molar tooth sign. The presence of this characteristic neuroimaging finding, is highly suggestive of JS diagnosis.

Discussion: Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g, pigmentary retinopathy, oculomotor apraxia and nystagmus), renal cysts and hepatic fibrosis. Respiratory abnormalities,such as apnea and hyperpnea, may be present, as well
as mental retardation. To date, published mutation screenings of known genes have allowed the identification of mutations in less than half JSRD patients, making prenatal diagnosis still limited to a subset of families.

CATASTROPHIC ENCEPHALOPATHY SOON AFTER CHEMOTHERAPY WITH RAPID OSMOTIC CHANGE IN A 10-YEAR-OLD GIRL WITH MIDLINE BRAIN TUMOR

Background and Highlight: Osmotic demyelination syndrome (ODS) is well known as a complication of rapid serum sodium correction. ODS can be divided into central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM). The classic presentations are mental status changes and rapidly progressive quadriparesis associated with dysphagia and dysarthria. The diagnostic test is MRI, which reveals symmetric hyperintensity on T2 and FLAIR within the pons in typical CPM, or within caudate and putamen in EPM.

Case Report: A 10-year-old girl with midline brain tumor, presented with acute loss of right eye vision in one week. Diabetes insipidus developed and was controlled with DDAVP. Cerebral salt-wasting-related hyponatremia induced a seizure episode 2 days after cisplatin and etoposide treatment. Serum sodium elevated rapidly or the next day.
Left hemiparesis occurred and extended to the right side as well as disturbed consciousness followed and progressed soon to comatous status. Serial brain MRI images revealed progressive hyperintensity changes over bilateral basal ganglia and bilateral cortices. Osmotic encephalopathy was highly suspected by clinical history and brain images.

Laboratory Data: Elevated urine sodium concentration (168mEq/L), hyponatremia (108mEq/L) and fair urine output (3.9ml/kg/hr) were compatible with cerebral salt- wasting syndrome. Serum sodium elevated to 147 mEq/L within 24hrs.

Discussion: The midline brain tumor caused the girl to have panhypopituitism and diabetes insipidus. The multiple etiologies resulted in the difficulty of clinical management, which led to poor control of the serum sodium and progressive encephalopathy. Osmotic encephalopathy might be the most likely cause and we would like to address the importance of close monitoring electrolytes during midline brain tumor treatment.