Child Neurology Unit Research Articles

Previously defined variants of uncertain significance may play an important role in epilepsy and interactions between certain variants may become pathogenic.

Epilepsy is a chronic neurological disorder related to various etiologies, and the prevalence of active epilepsy is estimated to be between 4 and 10 per 1000 individuals having a significant role in genetic mutations. Next-Generation Sequencing (NGS) panels are utilized for genetic testing, but a substantial proportion of the results remain uncertain and are not considered directly causative of epilepsy. This study aimed to reevaluate pediatric patients diagnosed with epilepsy who underwent genetic investigation using NGS panels, focusing on inconclusive variant findings or multiple variants of uncertain significance (VUSs). A subgroup of pediatric patients aged 0-25 years, diagnosed with epilepsy, who underwent genetic investigation with an NGS epilepsy panel at the Child Neurology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, between 2018 and 2022 through Invitae, was reevaluated. Patients with inconclusive variant findings or multiple VUSs in their test results were included. Genetic data were analyzed to identify potentially pathogenic variants and frequent genetic combinations. Two unrelated potentially pathogenic variants were identified in the SCN9A and QARS1 genes. A frequent genetic combination, RANBP2&RYR3, was also observed among other combinations. The RANBP2 gene consistently co-occurred with RYR3 variants in uncertain results, suggesting potential pathogenicity. Analysis of unaffected parents' data revealed certain combinations inherited from different parents, suggesting specific gene combinations as possible risk factors for the disease. This study highlights the importance of reevaluating genetic data from pediatric epilepsy patients with inconclusive variant findings or multiple VUSs. Identification of potentially pathogenic variants and frequent genetic combinations, such as RANBP2&RYR3, could aid in understanding the genetic basis of epilepsy and identifying potential hotspots. We have performed a retrospective analysis on a subpopulation of pediatric patients diagnosed with epilepsy. We found that specific genetic variants were repeatable, indicating their potential pathogenicity to the disease.

Guillain-Barrè Syndrome-Retrospective Analysis of Data from a Cohort of Patients Referred to a Tertiary Care Pediatric Neuromuscular Center from 2000 to 2017: Electrophysiological Findings, Outcomes, and a Brief Literature Review.

Background and Objectives: Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paresis in children. The aim of this study was to describe the clinical and electrophysiological findings and outcomes of children with GBS diagnosed in our unit. Moreover, the literature on pediatric GBS cases from the past 5 years was reviewed. In this retrospective study, we reported data on 12 patients (9 male and 3 female patients; mean age: 5 y, 4 mo; range: 9 mo-11 y) clinically diagnosed at the Child Neurology Unit of the AUSL-IRCCS of Reggio Emilia, Italy, between 2000 and 2017 and a brief analysis/comparison with data from the literature. Materials and Methods: Data were collected from medical charts. Results: In our cohort, male patients were more frequent than female ones (9 vs. 3), and upper respiratory tract infection (n = 8, 66.7%) was the most frequent triggering factor. The main clinical symptoms on admission were distal lower limbs' weakness with gait difficulties (83.3%), pain (50%), upper limbs' weakness (50%), and dysphagia for liquids (25%). Peripheral neurophysiological studies revealed acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 66.6% of the children, acute motor and sensory axonal neuropathy (AMSAN) in 25%, and acute motor axonal neuropathy (AMAN) in 8.3%. Ten individuals (83.3%) received timely treatment with intravenous immunoglobulins (IVIG), and, out of these ten patients, 58% received concomitant treatment with IV methylprednisolone because of a progressive disease course. Complete remission was observed in the majority of individuals (91.6%) within 6 months of symptom onset. Conclusions: Different subtypes of GBS can affect children; however, the outcome is usually positive. Early treatment appears to be important for a favorable outcome.

Functional tic-like behaviours during the COVID-19 pandemic: Follow-up over 12 months.

Functional tics are included in the wide spectrum of functional movement disorders (FMDs). Their distinction from organic tics is challenging because they both phenomenologically present common features. During the COVID-19 pandemic, there has been an increase in functional tic-like behaviours in vulnerable children and adolescents after social media exposure. This study explores the phenomenology and course of a cohort of newly diagnosed functional tic-like behaviors. We analysed clinical data of 243 patients affected by tic disorders collected at outpatient Tourette Clinic, Child and Adolescent Neurology and Psychiatry Unit, Catania University. Among the clinical cohort with functional tic-like behaviors, we evaluated the clinical course of symptoms at follow-up visits after 6 and 12 months. Among the cohort of 243 patients referred for evaluation at our centre, 11 were diagnosed with functional tic-like behaviours. The majority of participants with functional tic-like behaviours were female with a mean age of 15 years old and presented an explosive symptom's onset. At follow-up visit after 12 months, patients with functional tic-like behaviors showed a significant variation in the severity of tics and anxiety symptoms. Conversely, depressive, and obsessive-compulsive symptoms did not significantly differ during the follow-up. Our data suggest that several characteristics in clinical course and their phenomenology can help clinicians to distinguish functional tic-like behaviours from organic tics. Our results also suggest a better outcome for tics and anxiety symptoms respect on other comorbidities. A prompt diagnosis and management not only of tics but also comorbidities are recommended, as generally conventional pharmacotherapy for tics does not have positive effects on these patients.

Migraine Symptoms Improvement During the COVID-19 Lockdown in a Cohort of Children and Adolescents.

Background: Pediatric migraine is among the most common primary or comorbid neurologic disorders in children. Psychological stressors are widely acknowledged as potential triggers involved in recurring episodes of pediatric migraine. As the COVID-19 emergency may have affected the levels of stress perceived by children and adolescents with migraine, the present study was aimed to understand the effect of COVID-19 emergency on symptoms intensity and frequency in pediatric patients.Methods: A cohort of 142 child and adolescent patients with a diagnosis of migraine was enrolled at the Child Neurology and Psychiatry Unit of the IRCCS Mondino Foundation in Pavia (Italy). Socio-demographic and clinical characteristics were obtained from medical records. An on-line survey was used to collect information on COVID-19 exposure, stress response to the lockdown period, anxious symptoms during COVID-19 emergency, as well as migraine symptoms intensity and frequency before and during the lockdown.Results: The great majority were outpatients (n = 125, 88.0%), 52 (36.6%) had migraine with aura, whereas, 90 (63.4%) had migraine without aura. All the patients reporting worsening symptoms progression before COVID-19, had reduced intensity during the lockdown (χ2 = 31.05, p < 0.0001). Symptoms frequency reduction was observed in 50% of patients presenting worsening symptoms before the lockdown, 45% of those who were stable, and 12% of those who were already improving. All patients who had resolved symptoms before COVID-19 were stable during the lockdown (χ2 = 38.66, p < 0.0001). Anxious symptomatology was significantly associated with greater migraine symptoms frequency (χ2 = 19.69, p < 0.001). Repeating the analysis separately for individuals with and without aura did not affect the findings and significant associations were confirmed for both the patients' subgroups.Discussion: A significant reduction of migraine symptoms intensity and frequency was observed in pediatric patients during the COVID-19 lockdown phase in northern Italy. The improvement in both intensity and frequency of the migraine symptoms was especially significant in patients who were stable or worsening before the lockdown. The reduction of symptoms severity during a period of reduced environmental challenges and pressures further highlights the need of providing effective training in stress regulation and coping for these patients.

Paediatric-onset hereditary spastic paraplegias: a retrospective cohort study.

To describe the clinical and neurogenetic spectrum of paediatric-onset hereditary spastic paraplegias (HSPs) diagnosed in our unit. We report on 47 patients (30 males, 17 females; mean [SD] age 12y 7mo [6y 2mo], range 4-34y) clinically diagnosed with an HSP at the Child Neurology Unit, IRCCS-ASMN (Reggio Emilia, Italy) between 1990 and 2018, who were genetically investigated by means of single-gene direct sequencing and/or next-generation sequencing technologies (targeted panels, whole-exome sequencing [WES]). Complex forms prevailed slightly (n=26), autosomal dominant being the main inheritance pattern (n=11), followed by recessive (n=5) and X-linked (n=1). A definite genetic diagnosis was achieved in 17 patients. Spastic paraplegia 3A (n=4) was the most frequent cause of autosomal dominant HSP in our cohort, while no genetic variant prevailed in autosomal recessive forms and pathogenic/likely pathogenic variants were disclosed in a wide range of different genes. We found wide phenotypic and genetic heterogeneity. With increasing accessibility to WES, a higher number of patients receive a diagnosis, allowing detection of variants in ultra-rare disease-causing genes and refining genotype-phenotype correlations. A genetic diagnosis of paediatric-onset hereditary spastic paraplegia was achieved in one-third of patients. Pathogenic/likely pathogenic variants in rare genes were found. Genotypic and phenotypic heterogeneity favours targeted panel/whole-exome sequencing for diagnosis.

Chiari I malformation in defined genetic syndromes in children: are there common pathways?

Chiari malformation type I (CMI) is a common pediatric neurologic anomaly that can be associated with a variety of genetic disorders; however, it is not always clear whether the observed associations are real or random. The knowledge of the real associations could provide useful guidance to clinicians. Furthermore, it could be of help to better understand the still unknown genetic etiology of CMI. With the aim of implementing such insights, we retrospectively reviewed clinical, neuroradiological, and genetic data of patients harboring CMI evaluated at the Child Neurology Unit of our institution between January 2008 and December 2018. The cohort consists of 205 patients (111 males and 94 females), with a mean age at diagnosis of 6.3years (range 0-18years). 188patients completed an average follow-up period of 5.2years (range onemonth-18years). Mean age at last assessment was 11.4years (range ninemonths-23years). 127 (62%) children have been classified as syndromic due to the presence of neurodevelopmental disorders, phenotypic anomalies, or malformations. Among syndromic CMI children, a molecular diagnosis was identified in 35/127 (27.6%) (20 males and 15 females). The most common diagnoses were syndromic craniosynostosis in 8/35 children (22.9%), among which sevenare FGFR-related and one ERF-related craniosynostosis; disorders of the RAS/MAPK pathway, termed RASopathies or RAS/MAPK syndromes in 9/35 (25.7%); disorders of the PTEN-PI3K/AKT signal transduction cascade, termed PTENopathies in 3/35 children (8.6%); and chromosomal rearrangements in 6/35 patients (17.1%), two of whom with del16p11.2. We polarized our attention on the defined genetic diagnoses focusing not only on the phenotypic hallmarks but also on the phenotypic overlapping features. In addition, we discussed the pathophysiological mechanisms leading to progressive cerebellar ectopia and the involved molecular pathways. Along with the recent literature evidence, we suppose that interactions between FGFR and RAS/MAPK pathway and between RAS/MAPK and PTEN-PI3K/AKT pathways could explain some phenotypic overlapping features and could have a significant role in the pathogenesis of CMI.

Developmental dysplasia of the hip in children with a psychomotor disorder. A risk factor for a poor outcome?

Abstract Introduction Orthopaedic treatment of developmental dysplasia of the hip (DDH) has a high success rate in cases that are diagnosed early. However, the outcomes of these patients are not really known when they are subsequently diagnosed with some type of cerebral impairment. Materials and methods A retrospective observational study was conducted on cases of DDH with a poor outcome after orthopaedic treatment, being unknown if they had any type of psychomotor disorder. The patients were clinically and radiologically assessed, and afterwards received neurological valuation by the Child Neurology Unit. Results Of the 325 cases of DDH diagnosed in 293 patients, 10 patients (3%) with 16 hips with DDH were diagnosed of any cerebral impairment. All of them were initially treated orthopedically. Clinical and radiologically evolution was succesful only in 4 cases (25%) being necessary any surgical procedure in the remaining 12 cases. After surgical treatment we got an improvement in the Acetabular Index (p = 0.005) and Reimers Extrusion Index (p = 0.042). Neck-shaft angle and Wiberg CE angle also improved but this difference was not statically significant. Cerebral impairment was diagnosed at 2.5 years of age and the begining of walking was delayed at 2.4 years of age. Conclusions Cerebral impairment can lead to an unfavourable outcome in the treatment of DDH, with the relative risk of a poor outcome being 7.2 times higher in these patients. An unfavourable outcome with conventional treatment of DDH must make us suspect the presence of some type of neurological disorder, particularly if there is a delay in walking.

Cognitive-behavioral profiles in teenagers with Dravet syndrome

AimTo investigate behavior and cognitive performances of teenage patients with Dravet syndrome (DS). MethodsWe enrolled 20 teenage patients (12 females and 8 males) with DS, followed in the Child Neurology Unit of the Catholic University (Rome). Patients underwent a full clinical examination including behavioral and cognitive assessments (respectively, CBCL and Wechsler scales). ResultsAll patients showed behavior disorders and mental retardation, mild in six cases, moderate in seven and severe in the remaining seven. Among mildly retarded patients visual function, particularly visuo-motor abilities resulted mostly impaired in Wechsler subtests, whereas verbal skills were relatively preserved. In contrast, a general cognitive impairment was observed in moderately and severely retarded patients. ConclusionsOur teenage patients with DS compared with other series at different ages (young childhood, adulthood) suggest a progressivity of neurological and neuropsychological signs. A visuomotor default and a relative preservation of verbal skills, like what has been found in previous reports of younger patients, are still evident in mildly impaired cases. Therefore, the progression over time of these cases toward a generalized impairment may be suggested, but only longitudinal studies can confirm it.There was a possible responsibility of some epileptic disorders in worsening the neuropsychological outcome (early myoclonic seizures and atypical absences, as well as persistent EEG background slowness in the last 3years).

Disorders of early language development in Dravet syndrome.

The aim of this study was to investigate language disorders prospectively in patients with Dravet syndrome (DS) during the first years of life in order to identify their features and possibly the underlying mechanisms of the disease. At the Child Neurology Unit of Catholic University in Rome (Italy), thirteen patients with typical findings of DS were enrolled in the study. Full clinical observations, including neurological examination and long-term EEG monitoring, were prospectively and serially performed until a mean of 6years of age (range: 4years to 7years and 8months). The epileptic history was also collected in each case. In particular, developmental, cognitive, and detailed language assessments were performed with different tests according to the age of the patient. In addition to cognitive decline, characteristic language impairment was also found with a relative preservation of receptive abilities (comprehension) and a strong impairment of productive skills. This defect in sensorimotor verbal processing integration is discussed to highlight the possible mechanisms underlying cognitive decline.

Displasia del desarrollo de la cadera en niños con trastorno psicomotor. ¿Factor de riesgo para un mal resultado?

IntroductionOrthopaedic treatment of developmental dysplasia of the hip (DDH) has a high success rate in cases that are diagnosed early. However, the outcomes of these patients are not really known when they are subsequently diagnosed with some type of cerebral impairment. Materials and methodsA retrospective observational study was conducted on cases of DDH with a poor outcome after orthopaedic treatment, being unknown if they had any type of psychomotor disorder. The patients were clinically and radiologically assessed, and afterwards received neurological valuation by the Child Neurology Unit. ResultsOf the 325 cases of DDH diagnosed in 293 patients, 10 patients (3%) with 16 hips with DDH were diagnosed of any cerebral impairment. All them were initially treated orthopedically. Clinical and radiologically evolution was succesful only in 4 cases (25%) being necessary any surgical procedure in the remaining 12 cases. After surgical treatment we got an improvement in the Acetabular Index (p=0.005) and Reimers Extrusion Index (p=0.042). Neck-shaft angle and Wiberg CE angle also improved but this difference was not statically significant. Cerebral impairment was diagnosed at 2,5 years of age and the begining of walking was delayed at 2.4 years of age. ConclusionsCerebral impairment can lead to an unfavourable outcome in the treatment of DDH, with the relative risk of a poor outcome being 7.2 times higher in these patients.An unfavourable outcome with conventional treatment of DDH must make us suspect the presence of some type of neurological disorder, particularly if there is a delay in walking.

PP04.12 – 3020: Chromosomal rearrangements of 6p25.3 and Moyamoya syndrome: A non-incidental association

Objective To present a case carrying a chromosomal rearrangement of the 6p25.3 locus and diagnosed with Moyamoya syndrome. Methods A Caucasian 4 years-and-9-months-old girl was admitted to a peripheral hospital for vomiting and acute left hemiparesis, followed by left arm clonic seizures, aphasia and confusion. Phenytoin stopped the crisis, but hemiparesis persisted. EEG documented widespread slow waves, mainly on the right hemisphere. Computed tomography (third day) showed hypodensity of the entire right hemisphere. Past history was characterized by prematurity (born at 32 g.w.), cardiac defects (atrial septal defect, patent ductus arteriosus), surgically corrected at 3 years old. High resolution karyotype showed this rearrangement: 46, XX, der(6)dup(6) (p24p23)del(6)(p25). Cognitive level was borderline. On day 4 the girl was transferred to our Child Neurology Unit where she underwent a complete workup. Results Echocardiogram: normal; carotid doppler ultrasound: bilateral stenosis of internal carotid arteries; brain magnetic resonance imaging (MRI): ischemic areas in territories supplied by right middle and anterior cerebral arteries; brain angio-MRI: bilateral multiple stenosis of anterior and posterior cerebral arteries and collateral circulation consistent with Moyamoya syndrome. Therefore, after a digital angiography, the patient underwent an encephalo-duro-arterial-myo-sinangiosis. The post-operative period was uneventful. Conclusion Moyamoya syndrome is known to be associated to some genetic conditions (such as Neurofibromatosis type 1, Alagille syndrome and Trisomy 21). To date, only one pediatric case with Moyamoya syndrome and chromosomal rearrangement of 6p25.3 has been reported, similar to our patient. Therefore, all patients presenting with a chromosomal rearrangement involving the 6p25.3 locus should be studied with brain angio-MRI; moreover this genetic region should be investigated to identify possible disease-specific genes for Moyamoya syndrome.

PP05.15 – 2915: A case of neonatal onset leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) with rapid progression

Objective To present a case of LBSL with neonatal onset and with rapid progression and to review the literature focused on LBSL with early onset (before one year of age). Methods We report a case of an infant admitted at our Child Neurology Unit in November 2014 with LBSL, investigated with blood and cerebrospinal spinal fluid (CSF) tests, brain and spinal magnetic resonance imaging (MRI). Results The patient was admitted at our hospital at 2 months of age because of severe hypotonia. She had regular antenatal and perinatal story. At birth physical and neurological examination were normal. At two weeks of age nystagmus was noticed and after few weeks, she started to be hyporeactive and hypotonic. At our examination she had severe and diffuse hypotonia, brisk reflex at legs and nystagmus. CSF examination showed an increased lactate (7.4 mmol/L, range 1.2–2.2 mmol/L). Cerebral (including spectroscopy) and spinal MRI showed changes in white matter consistent with LBSL. Two weeks later she developed respiratory arrest and needed mechanical ventilatory support. Steroid therapy was administered without results. Genetic test is in progress. Conclusion LBSL is a rare disease described for the first time in 2003 by Van der Knaap et al. as a mild disorder with childhood and adolescent onset and slow progression. In the Literature we found two cases with neonatal onset, rapid deterioration and death respectively at 2 and 3 year of age and 16 cases with onset before 12 months (mean 8 months) and early death in 6/16 cases. We add to the pertinent literature a new case of LBSL with neonatal onset having a rapid and deteriorating course. This condition should be suspected in neonates or infants with leukoencephalopathy on brain MRI and lactic acidosis in CSF. Spinal MRI and specific genetic tests are needed to confirm the diagnosis.

PP09.14 – 2843: Congenital absence of gluteal muscles without spina bifida occulta: The first case report

Objective To present a case of congenital gluteal muscles absence associated with renal ectopia, without spina bifida occulta. Methods A 3-years-old child was referred to our child Neurology Unit for motor delay and walking difficulties. Familial and pregnancy history were unremarkable except for right renal ectopia diagnosed with antenatal ultrasound. At birth, he presented flexed hips and lower limbs rigidity. He started walking at 19 months. Neurological examination (28 months) showed waddling gait, gluteal muscles hypoplasia and lumbar hyperlordosis. Laboratory findings, imaging and electrophysiological exams were performed. Results At 28 months of age the child underwent electromyography (with needle of 50 mm) that showed absence of voluntary activity in the territory of gluteal muscles, with normal response in the regions of vastus medialis and sural triceps and normal nerve conduction studies. Laboratory findings (creatine phosphokinase and transaminases) were normal. Musculoskeletal and pelvis magnetic resonance imaging (MRI) revealed a complete, symmetrical fibroadipose replacement of gluteus, gracilis, semitendinosus, semimembranosus and biceps femoris muscles, anterior legs muscles were normal. Spinal magnetic resonance excluded spina bifida occulta. Right kidney was ectopic. Conclusion Bilateral symmetrical congenital absence of muscles is rare, other than Eagle-Barrett syndrome. So far, only three cases of congenital absence of gluteal muscles have been reported and they all had spina bifida occulta. To the best of our knowledge, our case is the first report of congenital absence of gluteal muscles without spinal dysraphism. The only remarkable finding was the kidney ectopia, never described in association with gluteus' agenesis by previous Literature. This association could be explained by a disruption of normal embryologic migration of mesodermal cells during gestational age. Muscular MRI and extensive electromyography should be considered in the diagnostic work-up of children with motor delay and walking difficulties and with clinical suspicion of neuromuscular disorders.

Correction: 24 Month Longitudinal Data in Ambulant Boys with Duchenne Muscular Dystrophy

There was an error in the affiliation of author Antonella Pini. The correct affiliation for this author is: Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy

Causes of developmental delay in children of 5 to 72 months old at the child neurology unit of Yaounde Gynaeco-Obstetric and Paediatric Hospital (Cameroon)

Background: According to the World Health Organization, about 5% of children world-wide of 14-year-old and under have a moderate to severe developmental disability, and up to 15% of children under 5-year-old are developmentally delayed. Purpose: To determine the prevalence, socio-demographic profile, aetiologies, and the clinical presentation of developmental delay in children less than 6-year-old at the child neurology unit in a university-affiliated hospital in Yaounde. Materials and methods: It was a crosssectional descriptive study carried out in Yaounde Gynaeco-Obstetric and Paediatric Hospital (Cameroon) from August to December 2012. Children aged between 5 - 72 months with a developmental quotient less than 70 were enrolled. Developmental delay (DD) was diagnosed and classified using the Denver developmental screening test (DDST). Data concerning the child (age, gender, severity of DD), the mother (age, age at conception, educational level, marital status), history of pregnancy and delivery, perinatal and postnatal events, results of para-clinical explorations (EEG, CT-scan, genetic tests), the severity of DD and the probable or demonstrate cause of DD were recorded on a standardized questionnaire. The chisquare test was used to compare variables. Results: During the study period, 2171 children aged 5 - 72 months consulted the paediatric department of the hospital, 296 were examined at the child neurology unit of which 153 had a developmental quotient less than 70, giving a hospital prevalence of 7.0% and a prevalence of 51.7% at the child neurology unit. The mean age was 26.6 ± 18.0 months and there were 56% males. The main reason for consulting was tonus disorder (43.8%) and the developmental area of parental concern was the motor domain (90.2%). Regarding the clinical presentation, 75.2% of our population were children with cerebral palsy. DD was severe, mild, moderate and profound respectively in 14.2%, 13.5%, 12.2%, and 11.1%. Gross DD represented 90.2% of all DD children. The causes of DD were hypoxic-ischemic encephalopathy (41.8%), epilepsy (13.7%), sequelae of meningitis (6.5%), sequelae of kernicterus (6.5%), and infectious embryofoetopathies (5.2%). Conclusion: Developmental delay is frequent in paediatric neurology, with perinatal disorders being the leading aetiologies in Cameroon. Prevention of perinatal hypoxic-ischemic encephalopathy risk factors needs to be reinforced.

Clinical, aetiological and evolutive aspects of West syndrome in Yaound&#233; (Cameroon)

Background: West syndrome (WS) is an epileptic syndrome of the infant occurring between the 3rd and 12th months of life and characterized by the triad: infantile spasms in flexion, extension or mixed; global developmental delay; and hypsarrythmia on the electroencephalogram (EEG). Its incidence varies between 2.9 and 4.5 per 10,000 live births. West syndrome is caused by a brain dysfunction whose origins can be prenatal, neonatal and postnatal. Sometimes the aetiology is genetic or unknown. Purpose: To determine the main clinical, aetiological and major evolutive aspects of West syndrome in child neurology unit in a university-affiliated hospital in Yaoundé. Materials and Methods: It was a retrospective descriptive study conducted from September 2011 to January 2012 inthe child neurology unit of the Yaoundé gynaeco-obstetric and paediatric hospital. The medical records of 68 children followed for West syndrome (WS) in the service during the period from February 2008 to January 2012 (48 months) were used. All infants of 1- to 16-month-old with the diagnosis of WS were included. The diagnosis of WS was based on clinical evidence of spasm in flexion and/or in extension with global development delay, and EEG evidence of hypsarythmia or focal/multifocal epileptic abnormalities when hypsarythmia is absent. For each included infant, relevant medical history and complete physical examination were performed. The following data were collected and reported on a standardized questionnaire: prenatal, perinatal and postnatal past histories, age at onset of spasms, age at diagnosis, semiology of spasms, psychomotor development, the EEG and CT aspects and the evolutive modes of WS under treatment. Psychomotor development was assessed using theDenverdevelopmental screening test (DDST) which assesses the mental age compared to chronological age. Results: The age of onset of spasms varied between 1 and 16 months with a mean of 4.69 (±1.98) months. Males were highly represented with a sex ratio of 1.72. Flexion spasms were the most common clinical presentation (79.41%). 82.83% of the patients had a global developmental delay on the onset of spasms. Structural causes or symptomatic West syndrome was the most frequent presentation (77.94%). Perinatal aetiologies were highly represented (73.58%) with the main cause being neonatal asphyxia (55.88%). A hypsarrythmic tracing was found on the electroencephalogram (EEG) in 73.53% of cases. The most frequent CT abnormality was cortico-subcortical atrophy (38.24%). At the end of our study, global developmental delay persisted in 89.72%. Conclusion: The main aetiologies of West syndrome in our context are the sequelae of neonatal asphyxia and viral embryofoetopathies. There is a high incidence of associated global developmental delay. More prevention methods on risk factors for foetal distress and proper monitoring of deliveries to minimize severe neonatal asphyxia are indispensable.

Clinical and therapeutic implications of psychiatric comorbidity in high functioning autism/Asperger syndrome: An Italian study

The present study describes the occurrence of psychiatric comorbid disorders in a cohort of 86 high functioning autism (HFA)/Asperger syndrome (AS) patients, examined at Child Neurology and Psychiatry Unit of Tor Vergata University. 38 patients out of 86 (44.2%) presented one or more psychiatric comorbidities, such as mood disorders, Attention Deficit/Hyperactivity Disorder (ADHD), Tourette syndrome (TS), anxiety disorders, including obsessive-compulsive disorder (OCD), and psychotic symptoms. We compared our sample with the evidences from the scientific literature on psychiatric comorbidity in ASD patient, in particular in HFA/AS. In this paper we focus on the high frequency of comorbid psychiatric disorders in HFA/AS patients, such as mood disorders, Attention Deficit/Hyperactivity Disorder (ADHD), Tourette syndrome (TS), anxiety disorders, including obsessive-compulsive disorder (OCD), and psychosis, including schizophrenia. We analyzed rates of all psichiatric comorbidities diagnosed in a sample of HFA/AS subjects and we compared findings from our study with the evidences from the scientific literature on psychiatric comorbidity in ASD patients, in particular HFA/AS. We point out that comorbid psychiatric symptoms can be hardly diagnosed, because they could present atipically in ASDs then in general population. Furthermore, they could be masked by ASD core symptoms.

Risk Factors of Poorly Controlled Childhood Epilepsy - A Study in A Tertiary Care Hospital

Objective: Identifying the risk factors of poor seizure control in children in a setting of tertiary care hospital. Design: Retrospective study. Setting: Child Development and Neurology Unit in the department of Paediatrics of Bangabandhu Sheikh Mujib Medical University (BSMMU). Study period: January 2004 through December 2005. Subjects: One hundred and twenty epileptic children were studied. They were grouped into controlled group (seizure free for more than six months) and poorly controlled group (having one or more seizure per month over a period of six months or more and who had experienced trials of at least two different antiepileptic drugs at optimum doses alone or in combination with adequate compliance) at the end of intervention and compared. Results: In this study 76 (63.3%) children were male and 44 (36.7%) children were female. Out of 120 cases 79 (65.8%) were in controlled group and 41 (34.2%) cases had poorly controlled epilepsy. Mean age of the controlled group and poorly controlled group of children were 79 months and 40.3 months respectively. Focal epilepsy was found in 30 (68%) cases in controlled and in 14 (31.8%) cases of poorly controlled group and generalized epilepsy was found in 42 (72%) cases in controlled and in 19 (28.8%) cases in poorly controlled group. Idiopathic epilepsy was more common which was 37 (46%) in controlled group against 14 (34%) in poorly controlled group. But symptomatic and cryptogenic cases were more prevalent with poorly controlled group 57.5% than controlled group 53%. In poorly controlled group 48.8% had cerebral palsy in comparison to 22.8% of controlled group. Early onset of seizure before one year was 25.3% in controlled and 78% in poorly controlled group (odds ratio=.2322, p =.0082) and one or more seizure per week 43% in controlled and 92.7% in poorly controlled group (odds ratio=.1218, p=.0032) were found as risk factors of poorly controlled epilepsy. Conclusion: Early onset of seizure before one year, symptomatic epilepsy and one or more seizure per week at diagnosis were found as risk factors of poorly controlled epilepsy in children attending a tertiary care hospital. DOI: http://dx.doi.org/10.3329/bjch.v34i2.10216 BJCH2010; 34(2): 44-50

Drug-resistant epilepsy and epileptic phenotype-EEG association in MECP2 mutated Rett syndrome

Objective To determine in MECP2-mutated Rett syndrome (RTT [MIM 312750]): (1) the prevalence of drug-resistant epilepsy (DRE); (2) whether the presence of DRE is related to the abnormal EEG patterns or to the particular MECP2 mutant genotype. Methods Retrospective survey of a large population of patients ( n = 154) evaluated between 1978 to 2007 (May) at the Child Psychiatry and Neurology Unit of Siena (Italy) with both clinical and genetic (i.e. MECP2 mutated) diagnoses of RTT. Some subjects were followed for up to 20 years. Among those, cases with epilepsy were first selected for study; within that group, cases with DRE were identified and studied. The association between clinical severity of their epilepsy and quantitative or qualitative scores of EEG severity was tested using rank coefficients (Spearman’s rho values). The relationship between DRE and RTT genotype category (i.e. gene deletion, gene duplication, early truncating mutation, late truncating mutation, and missense mutation) or a specific MECP2 genotype was tested using the chi-square test. A p-value <0.05 (two sided) was considered to indicate statistical significance. Results Prevalence of DRE was 16% (i.e. 16 DRE out of 100 MECP2-mutated RTT epileptic patients). No significant relationship was found between clinical severity of DRE and quantitative ( p = 0.9190) or qualitative EEG scores ( p = 0.1511). In addition, no significant relationship was found between the DRE and the RTT genotype category (chi-square = 1.147, DF = 4, p = 0.8867), or a specific MECP2 genotype (chi-square = 30.958, DF = 39, p = 0.8173). Conclusions Although RTT MECP2-mutated patients suffer from a serious and progressive encephalopathy, it is “epileptogenic” but not “DREgenic” as they have a decreased risk (16%) for DRE compared to the general epileptic population (DRE: 20-40%). The presence of DRE is not related to abnormal EEG findings or a particular MECP2 mutant genotype. Significance These observations could be of help in the practical management and family counseling.

IAP014 Tetanus in an unvaccinated child: oral baclofen treatment for muscle spasms

s: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress 59 IAP014 Tetanus in an unvaccinated child: oral baclofen treatment for muscle spasms E.C. Dinleyici2, A. Yakut1 *, C. Yarar1, R. Ulus2, B. Kirel2. 1Department of Pediatrics, Child Neurology Unit, 2Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine,