Journal of pediatric neurology: JPN

Published by IOS Press
Online ISSN: 1304-2580
Publications
Comparison of number of quadrants of optic disc swelling with outcome.  
Article
Raised intracranial pressure is a feature of cerebral malaria in children living in Africa. We investigated specific clinical optic disc features of papilledema to establish their prognostic significance in this encephalopathy. We developed a classification of acute papilledema and tested it against disease outcome. Kenyan children admitted with severe falciparum malaria (cerebral or impaired consciousness) underwent dilated fundal examination using direct and indirect ophthalmoscopy. Clinical features of the optic disc were systematically recorded and compared to the child's outcome. Poor outcome defined as death or neurological impairment on discharge was used to construct and test a clinical classification of papilledema. Forty-five children were examined (26 cerebral malaria, 17 severe malaria with an impaired conscious level or prostration) of whom seven had a poor outcome (three died, four had residual neurological impairment). Loss of the optic disc cup and marked optic disc elevation were significantly correlated with a poor outcome (P < 0.05). Increasing severity in the proposed classification of acute papilledema was positively correlated with a poor outcome (P < 0.05, chi-square test for trend). Loss of the optic disc cup and marked elevation of the optic disc head appear to be correlated with poor outcome in children with severe malaria whereas the presence of dilated veins suggests a good outcome. The proposed classification of acute papilledema is useful as a prognostic indicator and may be applicable to other encephalopathies with raised intracranial pressure.
 
Article
Trisomy 21, leading to Down syndrome (DS) is the most common genetic cause of intellectual disability. Approximately 1-13% of children with DS have co-morbid seizures, with infantile spasm being the most frequent type of seizure identified. Although the clinical and electroencephalography findings of infantile spasm are similar between children with DS and typically developing children, there is often a delay in the diagnosis of these seizures in children with DS. We present the case of a male infant with DS, where the diagnosis of infantile spasm was delayed by 5 mo. His case was associated with developmental regression and intractable seizure activity following diagnosis. The case highlights the implications of delayed diagnosis on treatment strategies and developmental outcomes. Keywords: Down syndrome, infantile spasm, delayed diagnosis.
 
Article
Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain malformation of the posterior fossa, typically resulting in developmental delay and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is relatively uncommon; thus, its impact on developmental outcomes has not been fully elucidated. Herein, we report a case of a 37-month-old child with DS and DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As such, it is important to determine how the DWS influences developmental outcomes, and appreciate the importance of early interventional therapy.
 
Article
Neonatal seizures are inherently different from seizures in the child and the adult. The phenotype, often exhibiting electroclinical dissociation, is unique: neonatal seizures can be refractory to antiepileptic drugs otherwise effect for older patients. Recent experimental and human-based research reveals that the mechanism of neonatal seizures, as well as their long-term sequelae on later brain development, appears to involve a large number of age-specific factors. These observations help explain the resistance of neonatal seizures to conventional therapy as well as identify potential areas of risk for later neurocognitive development. Emerging targets from this research may suggest new therapies for this unique population of patients.
 
Article
Objective This study aimed at evaluating serum S-100B protein levels after convulsions in children experiencing simple febrile convulsions. Material and Methods The study included 30 healthy children as the control group and 30 patients with simple febrile convulsions as the study group. Blood samples were obtained within 2 hours after the patients sustained febrile convulsions. Serum S-100B protein levels of the patients in the study group and the control group were measured using enzyme-linked immunosorbent assay kits. Results There was no statistically significant difference between the groups, when the mean serum S-100B protein levels were compared between patients with febrile convulsions and the control group (p > 0.05). Conclusion Lack of an increase in serum S-100B protein levels of patients with simple febrile convulsion suggests that febrile convulsive seizures do not cause any organ damage.
 
Article
Here we describe clinical and cytogenetic data on 2-year-old female child with partial trisomy for the distal part of the long arm of chromosome 10 (10q22->qter) and a concomitant monosomy 3(p25->pter) as a result of a maternal balanced reciprocal translocation. Her karyotype was ascertained as 46,XX,der(3)t(3;10)(p25;q22). The father had normal karyotype. The mother had an apparently balanced translocation involving chromosome 3 and 10 [46,XX,t(3;10)(p25;q22)]. This is the second reported case of partial trisomy 10q and partial trisomy 3p. Clinical features of this case and a few published cases will be reviewed briefly.
 
Article
Dravet syndrome is a severe form of epilepsy and also is called severe myoclonic epilepsy of infancy (SMEI). It appears during the first year of life with frequent febrile seizures, fever related seizures, which is rare beyond the age of 5 years. Children with SMEI typically experience poor development of language, motor skills, hyperactivity, and difficulty in making relationship. Thirty to eighty percent of patients with Dravet syndrome, which is known as classical form of SMEI, suffer from defects in a gene involved in proper function of brain cells. The patient is a 3-years-old girl presenting with a sudden epileptic seizure. She had 2-year history of severe myoclonic epilepsy and developmental delay that was diagnosed as Dravet syndrome. A novel missense substitution in sodium channel alpha subunit type 1 was detected and the novelty of substitution confirmed by molecular analysis in healthy family members as well as control group. As an early diagnosis, the clinical screening procedure used by pediatricians as well as a sodium channel alpha subunit type 1 mutation analysis could help to predict Dravet syndrome before 1 year of age, so the pediatricians could be able to manage clinical work-up properly.
 
Article
Congenital hypotonia and hypoventilation is a rare association. We report a rare case of a female newborn with poor respiratory drive, ventilator dependency, severe hypotonia, cardiomyopathy, and premature death. Clinical-exome-sequencing revealed SLC25A4-related mitochondrial deoxyribonucleic acid (DNA) depletion syndrome-12A (cardiomyopathic type). This syndrome is apparent at birth and carries a poor prognosis.
 
Article
The aim of this study was to analyze the various midline structures having preponderance for astrocytoma, their incidence, clinical features, operative approach, prognosis, and outcomes in children. It is a retrospective analysis of 152 cases with midline astrocytic tumors in children admitted between January 1995 and December 2012 in the Department of Neurosurgery at Sanjay Gandhi Postgraduate Institute of Medical sciences Lucknow, India. The mean age of the cases with midline astrocytic tumors was 9.29 ± 4.56 years. Majority of these tumors occurred in the age group of 6 to 10 years (n = 58, 38.16%), with male to female ratio being 1.66:1. Out of 152 cases, tumors located at midline cerebellum constituted majority of the cases (n = 38, 25%) followed by brain stem (n = 28, 18.42%), thalamic region (n = 24, 15.79%), corpus callosum (n = 18, 11.82%), pineal region (n = 12, 7.89%), optic nerve (n = 12, 7.89%), chiasmo-hypothalamic (n = 10, 6.58%), and septum pellucidum astrocytomas (n = 10, 6.58%). Majority of these tumors were of low-grade type (n = 136, 89.47%), and pilocytic astrocytomas were the commonest subtypes. Out of 152 cases, 136 (89.47%) cases had improved outcomes, 8 (5.26%) remained as they were in preoperative state, and mortality was seen in 8 (5.26%) of the cases at 3 to 77 months (mean 26.70 ± 9.70) of follow-up. Midline structures having preponderance for astrocytomas were midline cerebellum, brain stem, thalamus, corpus callosum, pineal region, optic nerve, chiasmo-hypothalamic, and septum pellucidum. Cerebellum was the commonest site. Most of these astrocytomas were of low grade with pilocytic astrocytoma being the commonest subtype. With meticulous presurgical planning, most of these tumors have good outcome with significant reduction in mortality and morbidity.
 
Article
Retropharyngeal neurofibromas are rarely described in the literature and are commonly associated with severe airway-related symptoms. We report a unique case of a large retropharyngeal plexiform neurofibroma in an asymptomatic 17-year-old male patient. This patient was asymptomatic and presented for lower lip edema secondary to an insect bite. Head and neck imaging demonstrated an extensive retropharyngeal neurofibroma measuring 5.7 cm × 2.2 cm × 6.8 cm. Because of extensive involvement of cervical vasculature, the lesion was not resected in our institution and his care was referred to a large neurofibromatosis type I center.
 
Article
In here, we describe a case of primary amenorrhea in the setting of chronic hydrocephalus caused by a posterior fossa ependymoma. A 17-year-old female with primary amenorrhea presented to University-affiliated teaching hospital. Hormonal studies were all normal. Cranial magnetic resonance imaging revealed chronic hydrocephalus with a 4 cm brain lesion that was determined to be an ependymoma. After surgical resection, the patient had normal menstrual cycles. Primary amenorrhea in association with hydrocephalus is usually due to hypothalamic hypogonadism. We report a case of an adolescent female with normal gonadotropin levels and chronic hydrocephalus who presented with primary amenorrhea. Even in the presence of normal hormonal studies and withdrawal bleeding after a progestational challenge, a head magnetic resonance imaging should be performed in all females who do not have hypergonadotropic amenorrhea.
 
Article
Glucose transporter deficiency syndrome type 1 (Glut-1 DS) is a rare disease of abnormal glucose transport. Diagnosis is most often made in infancy with the presentation of epileptic seizures, gross motor delays, and microcephaly. We report a case of a 17-year-old male seen in our outpatient clinic with a life-long history of developmental delays and seizures. He began having apneic episodes with limb jerking at approximately 4 months of age. Several antiepileptics were tried before the frequency of seizures decreased in early adolescence. Developmental delays became apparent in infancy. The proband's chief complaint at the time of presentation was abrupt episodes of confusion, fatigue, and ataxia, with body stiffening, occurring monthly, sometimes weekly, with minimal recollection of the event. At the time of his current evaluation, a review of laboratory findings revealed a low cerebrospinal fluid glucose level obtained during an emergency room evaluation for a headache several years prior. This finding raised concern for Glut-1 DS. Subsequent molecular analysis confirmed the diagnosis. While rare, this case emphasizes the importance of considering Glut-1 DS in the differential of seizures and cognitive delays, even in older children. Treatment with a ketogenic diet, despite at a later age of introduction, may still be effective in ameliorating symptoms.
 
Article
We report a case of an 18-month-old child who presented with motor predominant delay in attaining developmental milestones and early onset fatiguable weakness with ptosis and ophthalmoparesis. This ptosis and ophthalmoparesis typically worsened with progression of the day. Examination showed proximal weakness with preserved muscle stretch reflexes. Electrophysiology showed characteristic decrement on repetitive nerve stimulation test that localized to disorders of the neuromuscular junction. Next-generation sequencing showed a pathogenic variant of CHRNE that was responsible for congenital myasthenic syndrome. Such variants show increased improvement with salbutamol in addition to anticholinesterase inhibitors. Hence, the child was started on pyridostigmine, and the plan was to add on salbutamol on follow-up if optimal improvement does not occur.
 
Article
Evaluation of acquired demyelinating syndrome (ADS) without diagnostic biomarkers results in diagnostic and therapeutic challenges in pediatric population. Immune-mediated ADS of childhood responds well to steroid and intravenous immunoglobulin (IVIg) and in refractory cases with plasma exchange. Novel coronavirus disease 2019 (COVID-19) coinfection in such cases imposes technical challenges in management. An 11-year-old girl with quadriparesis and loss of vision and a magnetic resonance imaging (MRI) brain showing acute demyelinating encephalomyelitis (ADEM) and cerebrospinal fluid examination being noncontributory responded well with plasma exchange after failing steroid and IVIg is described. Coinfection with COVID-19 mandating personal protection in a temperate country imposed technical challenges in her management.
 
Article
Neurologic manifestations of severe acute respiratory syndrome coronavirus 2, the virus responsible for novel coronavirus 2019 (COVID-19) infection, have been frequently reported in the adult population but remain relatively rare in pediatric patients, specifically in regard to cerebrovascular accidents (CVAs). We present the case of a previously healthy 16-year-old adolescent boy with no preceding infectious symptoms who developed acute onset of left-sided weakness and slurred speech subsequently diagnosed with acute ischemic stroke (AIS). After performing a thorough diagnostic work-up, no clear etiology for AIS was identified. He was found to be COVID-19 positive by reverse transcription polymerase chain reaction upon admission. Accumulating evidence supports a link between COVID-19 and a systemic prothrombotic state suggesting pediatric patients who present with AIS and no other risk factors should be screened for this novel virus and potentially for extracranial sources of thrombi. As the rates of positive COVID-19 infection increase in the pediatric population, pediatricians and other pediatric subspecialists should be aware of the potential neurological and cerebrovascular complications of this novel virus to avoid delays in evaluation and intervention.
 
Article
This report presents the case of acute disseminated encephalomyelitis in a 2-year-old patient following a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test. She presented with ataxic gait, truncal ataxia, and reduced coordination following 10 days of intermittent fever and lethargy. She did not have any respiratory symptoms. Magnetic resonance imaging of the brain and spine showed widespread T2 high signal within the gray and white matters and within the spinal cord. She was treated with intravenous methylprednisolone followed by tapering oral prednisolone; this led to resolution of her neurological symptoms. This case highlights that neurological complications can occur secondary to SARS-CoV-2 infection.
 
Article
Pediatric inflammatory multisystem syndrome temporally associated with coronavirus disease 2019 (COVID-19) is an emerging rare disease reported in children 4 to 6 weeks after a usually asymptomatic COVID-19 infection. Though it usually presents as a Kawasaki-like illness or toxic shock syndrome, other multisystem presentations have been reported. Presentation as hemiplegia, however, is rare. Here, we describe a child with acute hemiplegia and rapidly progressive shock, who responded dramatically to steroids and intravenous immunoglobulin and experienced a full recovery. By reporting this case, we wish to add to the literature this atypical presentation of this novel disease, and highlight the importance of quickly diagnosing and treating this life-threatening disease.
 
Article
Idiopathic toe-walking (ITW) is considered a diagnosis of exclusion for which no underlying neurological, neuromuscular, neurodevelopmental, or orthopedic condition can be identified. The purpose of this review was to examine multiple aspects of ITW: natural history, evaluation, treatment, musculoskeletal manifestations, and developmental issues through the review of studies from the initial description of condition in 1967 to the present. From a PubMed search and review of reference lists of individual articles, 64 articles were selected and reviewed. The studied samples were variably described and often not well-defined. Gait analysis found gait characteristics associated with ITW that varied from normal. Children with ITW can be differentiated from children with cerebral palsy on the basis of several gait pattern features, but findings from electromyographic comparisons were variable. Treatments included orthoses, casting, botulinum toxin type A, and surgery. The evidence to support any specific treatment is limited by the small sample size and short duration of follow-up in the majority of studies. The inadequacy of the current literature suggests the need for a longitudinal multi-center study to more clearly define the population of children with ITW and to determine indications, timing, and effectiveness of the various available treatments.
 
Article
Proinflammatory cytokines play a role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). We aimed: 1) to characterize the expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the cerebrospinal fluid (CSF) of term infants with HIE, and 2) to determine the impact of a single dose of magnesium sulfate (MgSO4) on their concentrations. We analyzed the samples of CSF that were collected during a randomized controlled trial on the use of MgSO 4 in neonatal asphyxia. Two samples were obtained from each subject; one was obtained on admission and the second sample was collected at 72 hr of life. The grades of HIE in the 47 included newborns were mild (n=15), moderate (n=17), and severe (n=15). After the collection of the first CSF sample, 23 newborns received a single dose of MgSO4, whereas the other 24 newborns received an equal volume of normal saline placebo. Concentrations of IL-1β, IL-6 and TNF-α in the CSF were quantified by enzyme-linked immunosorbent assay in all CSF samples. The initial concentration of IL-1β and IL-6 correlated with the severity grades of HIE (P= 004 and P=0001, respectively) while TNF-α did not. At 72 hr, a significant decline in the concentration of TNF-α (pg/mL) was observed in samples of MgSO 4-treated infants when compared to the control group (-28 ± 90 vs. 102 ± 404, P=0.01), whereas the two treatment groups did not differ in IL-1β or IL-6. Short-term clinical outcomes correlated best with IL-1β at baseline, IL-6 at baseline and IL-6 at 72 hr. We conclude that cytokine activation, as manifested by increased IL-1β and IL-6 in the CSF, is positively correlated with the severity of HIE. Treatment with a single dose of MgSO4 was efficacious in aborting the activation of TNF-α but did not alter the expression of IL-1β or IL-6.
 
Article
This study was conducted to evaluate the clinical profile and predisposing factors of cerebral palsy (CP) in Jordanian children. Two hundred Jordanian children born between 1990 and 2005 with CP were reviewed in three teaching hospitals to study prospectively and retrospectively their clinical profile, possible etiological factors, and associated problems. A data collection sheet was developed to collect information from the children's parents, or occasionally from the chart regarding the demographic characteristics, detailed history, findings of the physical, developmental and neurological examination. Spastic CP was the predominant type (64.5%) with a quadriplegic CP being the most common (36%). Dyskinetic CP was present in 10.5%, while ataxic in 18%. In congenital CP, birth asphyxia constituted a significant possible cause (33.5%). Epilepsy is one of the most common associated problems among CP children constituting 56%. The results of our magnetic resonance imaging findings showed that only 15.5% of the children were normal. This was the first study which detailed the clinical spectrum of CP in Jordan. We concluded that the clinical spectrum of CP in our developing countries may differ from that of the developed countries.
 
Article
Developmental delay occurs when children fail to reach their developmental milestones at the appropriate time. The aim of this study was to determine the prevalence of developmental disorders as well as their correlations with selected demographic factors affecting development in children 4 to 60 months old in Khorramabad, Iran from 2015 to 2016. In this cross-sectional study, 500 children from 4 to 60 months of age and visiting health service centers were selected. Developmental status was measured using the Ages and Stages Questionnaire, and supplementary data were collected by separate questionnaires. Data were analyzed by the SPSS software using the independent t-test, chi-square test, and Mann–Whitney U test. Note that 8.6% of the children assessed in this study had developmental disorders. The mean age of the children in the normal group was 21.95 ± 16.42 months and in the developmental delay group was 16 ± 13.46 months. The highest prevalence of developmental delay was in the fine motor area (4.2%) and the lowest was in the personal–social area (1.4%). There were correlations between developmental disorder and the child's age (p = 0.006), birth order (p = 0.02), mother's education (p = 0.007), and father's education (p = 0.002). The parents' age, familial marriage, history of developmental disorders in the family, and the child's gender were not correlated with developmental disorders. Due to the high prevalence of developmental disorders and the importance of early identification and intervention, it is necessary to diagnose developmental disorders at early ages.
 
Article
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is one of the most common genetic syndromes. The varying presentation and severity of this syndrome result in diagnostic delays, especially in patients without cardiac malformation or characteristic features. We report a noncardiac case of 22q11.2DS with white matter abnormalities and velopharyngeal insufficiency. The recognition of white matter abnormalities as a feature of 22q11.2DS contributed to early diagnosis. Diagnostic delay could lead to inappropriate management and unfavorable outcomes. Increased awareness of the various minor features of 22q11.2DS may enable clinicians to diagnose this syndrome earlier and provide appropriate medical management.
 
Article
Chromosomal microdeletion syndromes are frequently associated with neurological disease including epilepsy and behavioral abnormalities. Yet, for most microdeletions, neurological phenotypes are variable and the exact molecular cause of neurological disease is not yet understood. Terminal deletions in the long arm of chromosome 2 (2q37.3) are among the most common microdeletion syndromes diagnosed, and have been associated with epilepsy, autistic-like features, short stature, obesity, and brachydactyly type E (short 4th and 5th metacarpals and metatarsals). However, neither epilepsy nor any of the other clinical features are invariant in 2q37.3 deletion. To elucidate the genetic mechanisms underlying this clinical variability we report what is, to our knowledge, the first description of inherited 2q37.3 deletion (without other complex chromosomal rearrangements) in three family members and present two sporadic cases and accompanying chromosomal microarray data. The clinical features of the three familial and two sporadic cases combined with the chromosomal microarray results suggest that all of the clinical features seen in 2q37.3 deletion may be variably expressed.
 
Article
We report a case of a 31-month-old girl with visual impairment. Magnetic resonance imaging showed a large cystic lesion with a mural nodule in the suprasellar region. Biopsy was performed, and histopathological examination demonstrated an atypical extraventricular neurocytoma (EVN). EVN is a rare neuroepithelial tumor with similar histological and biological characteristics in comparison to intraventricular neurocytoma. However, the morphological appearance of EVN can show wide variability with significant overlap of imaging findings compared with other neoplasms. The majority of EVNs are seen supratentorial involving the cerebral hemispheres. An EVN in the sellar or suprasellar region has only been reported twice in adults and to our knowledge never in children.
 
Article
Twin birth may represent a challenging event often associated with prematurity. We previously reported on developmental trajectories in preterm children categorized by gestational age. Based on the same study population, in this study we investigated the influence of gemellarity on the neurodevelopment of 73 twins (26.4%) and 207 singletons (73.6%), categorized into three groups according to their gestational age. The age of the achievement of developmental milestones between the three groups and the influence of preperinatal events on neurodevelopment were analyzed. An early neurodevelopmental advantage was detected in preterm twins born between 32 and 33 weeks. Environmental and nurturing factors may explain these findings.
 
Article
Neurocysticercosis (NCC) is the most common central nervous system parasitic disease worldwide, but cysticercal meningitis and intraventricular lesions are relatively rare, especially in Indian patients. Disseminated NCC with numerous cysts may give rise to the so-called "starry-sky" appearance on neuroimaging studies. Magnetic resonance imaging allows optimal identification of scolex and visualization of extraparenchymal cysts. We herein report a girl with multiple NCC (more than 400 lesions) with intraventricular involvement, but without focal neurological deficit on examination.
 
Article
Charcot-Marie-Tooth (CMT) disease is a group of clinically and genetically heterogeneous peripheral neuropathies by causing distal muscle weakness, sensory impairment, hyporeflexia, and skeletal deformities. Both of sequence and copy number variations (CNVs) of over 80 genes have been described in CMT patients so far, and FGD4 variants are among the uncommon causes of the disease. In this article, we present four siblings with early-onset CMT, who were found to carry a novel homozygous deletion within FGD4 gene by exome sequencing. Since CNVs of CMT-related genes other than PMP22 have been rarely described in literature and they are prone to be overlooked by next generation sequencing, this report confirms the importance of paying additional attention to these variants to increase diagnostic yield in CMT.
 
Article
Two siblings with an unbalanced cytogenetic composition are described: a brother with partial trisomy 5p and distal 15q microdeletion, and a sister with partial monosomy 5p and distal 15q microduplication, resulting from a familial balanced translocation 46,XY; t(5;15)(p14.2;q26.2). To our best knowledge, there are no previous clinical and cytogenetic reports in the literature describing a family with concomitant presence of such a unique mirror combination. Clinical features of pure imbalances and the effects of their combination are discussed.
 
Article
This study was conducted to study the perioperative findings in patients of spinal dysraphism. This observational study was conducted in Neurosurgery Department of Post Graduate Medical Institute, Lady Reading Hospital, Peshawar from January 2008 to December 2009. All the patients of spinal dysraphism less than 2 years of age were included in this study, while patients with ruptured spinal dysraphism at the time of presentation and with concomitant established hydrocephalus were excluded. Data was collected and analyzed by descriptive statistics using software SPSS version 17. Out of 96 patients operated for spinal dysraphism; 62 (64.58%) were males and 34 (35.42%) females. Eighty three patients (86.45%) were less than 1 yr, while 13 (13.54%) were above 1 yr. Peri-operative findings were: myelomeningocele in 50 (52.08%) patients, meningocele (MC) in 29 (30.20%), lipomyelomeningocele in six (6.25%), lipoma of cord with tethered cord in five (5.2%), MC with tethered cord in three (3.12%) patients, diastematomyelia in two (2.08%), while dermal sinus was found in one (1.04%) patient. In patients of spinal dysraphism less than 2 yr of age, more than 2/3rd of the patients presented with myelomeningocele and MC, while other features (such as lipomyelomeningocele, lipoma of cord with tethered cord, MC with tethered cord, diastematomyelia and dermal sinus) comprise only less than 20% of the spectrum.
 
Article
Genetic mutations are the underlying etiology of multiple neurodevelopmental disorders; some of which are associated with unique features on brain magnetic resonance imaging. Although the number of new mutations related to developmental impairments is steadily growing given the increased accessibility to advanced technologies, the mainstay of diagnosis still relies on physical examination and distinct presentation on brain imaging. We present the first report of cystic brain lesions associated with 9q21.13q21.32 microdeletion. The deletion overlapped with 11 RefSeq genes, including 3 OMIM Morbid Map genes. The clinical phenotype and the presence of periventricular cysts were unique and did not correlate with any disease known to be caused by a mutation in the region. We suggest that a few genes in the deleted region may be strong candidates implicated in neurodevelopmental disorders and the formation of cystic brain lesions.
 
Article
Ischemic stroke in children is rare when compared to adults; however, it is still among the 10 top causes of death in childhood and is more common than brain tumors. The pathology and the risk factors of stroke in children still remains poorly understood. Previous studies on Polish children after ischemic stroke showed that about 70% of them had dyslipidemia. Thus, looking for genetic factors associated with ischemic stroke in children, we decided to analyze some polymorphisms in genes involved in lipid metabolism. The aim of the study was to evaluate the possible association between the R219K polymorphism of the ABCA1 gene and the Q192R polymorphism of the PON1 gene and ischemic stroke in children. The study population consisted of 250 individuals, white Polish Caucasians, including 60 children with ischemic stroke, 120 their biological parents and 70 children without any signs of ischemic stroke. Polymorphisms were genotyped using the polymerase chain reaction-restriction fragments length polymorphism method. To analyze the possible association between the studied polymorphisms and stroke the transmission/disequilibrium test and the case-control model were used. We did not observe any preferential distribution of any allele of the analyzed polymorphisms from parents to the affected children. The number of transmitted alleles of both genes did not differ significantly from expected 50%:50%. There were also no significant differences in genotypes and alleles distribution between patients and control children. The results of our study suggest that neither the R219K polymorphism of the ABCA1 gene nor the Q192R polymorphism of the PON1 gene may be regarded as genetic risk factors for ischemic stroke in Polish children.
 
Article
Cranial nerve lesions often accompany head trauma. Olfactory, facial and vestibular nerves are the most commonly injured nerves. Optic and oculomotor nerve injuries are less frequently involved, and trigeminal, abducens and lower cranial nerves are rarely involved. The injury may occur in central nervous system or in the lower motor unit. Traumatic bilateral abducens paralysis is a very rare occurrence. It may follows cervical spine trauma and sixth nerve avulsion has been reported to complicate lumbar puncture. In this study, we describe an 11-year-old boy with bilateral abducens paralysis following hematoma in the left ponto-cerebellar angle and hemorrhage in the prepontine cisterns due to head trauma. Such hemorrhages might result in lesions in the supranuclear regions by traction on the nerve due to displacement of the pons and its nucleus as a result of direct pressure.
 
Article
Marinesco-Sjögren syndrome (MSS) is a multiorgan disorder firstly described in 1931 by Gheorge Marinescu. During the last seven decades, research into the clinical picture of MSS has led to the description of varying MSS phenotypes and since 2005, it is known that mutations within the SIL1 gene cause MSS in a part of these patients. Among these "SIL1-related MSS cases", "classical and non-classical phenotypes" are distinguished. All "SIL1-related MSS cases" show at least an ataxia due to cerebellar atrophy, congenital or infantile cataracts and a progressive myopathy as well as mental impairment ("classical MSS phenotype"). Additional clinical features are for example in some cases short stature, hypogonadism, scoliosis, nystagmus and strabismus ("non-classical MSS phenotype"). However, the primary pathology has remained unknown in non-SIL1-related MSS cases. As the clinical features detected in "classical MSS phenotype" and "non-classical MSS phenotype" may also be associated with cryptic subtelomeric rearrangements and as a frequent localization of for example cataract-related genes/loci within these regions is proven, we performed subtelomere screening in a series of 23 patients with "non-SIL1-related non-classical MSS phenotypes" presenting with at least three features like early cataracts, mental retardation, brain malformations, muscular hypotonia, growth retardation and skeletal abnormalities. Karyotype and the SIL1 coding sequence were normal in all cases. Subtelomere screening by multiplex ligation-dependent probe amplification did not identify any subtelomeric imbalances. Therefore, a causative role of these regions in manifesting "non-SIL1-related non-classical MSS phenotypes" seems to be unlikely.
 
Article
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that demonstrates variable severity, such that affected family members may have mild or severe disease. We performed exome and RNA sequencing of blood leukocytes from mild and severe cases across four families to identify mTOR pathway aberrations that may underlie phenotypic variability. In each family, we identified TSC1/TSC2 aberrations along with different mTOR pathway gene alterations, including base substitutions, deletions, and skewed allelic frequencies. Here, we describe the first reported DNA and RNA analysis of TSC families demonstrating mTOR pathway aberrations in mild and severe forms of the disease.
 
Article
Transcobalamin II (TCII) is a transporter protein that facilitates cobalamin release from the bloodstream to the cell. Deficiency in TCII is an autosomal recessive disorder caused by a mutation in the TCN2 gene. Treatment with intramuscular injection of hydroxocobalamin is greatly effective in improving the symptoms of this disorder. However, abnormal involuntary movements can occur and have been reported in patients with cobalamin deficiency caused by nutritional deficiency. Though, it is rarely associated with the treatment of hereditary TCII deficiency. Here, we report such a case, aiming to alert practitioners treating hereditary TCII deficiency. A 2-year-old boy born to a consanguineous parents presented with failure to thrive, recurrent infection, and pancytopenia. His condition deteriorated rapidly, and his investigation was remarkable for pancytopenia, elevated methylmalonic acid, and myelodysplastic changes in the bone marrow. A flash whole-exome sequence confirmed the diagnosis of TCII deficiency. The patient began treatment with IM hydroxocobalamin, and on the second day, he developed an abnormal involuntary movement that was abated by clonazepam. Abnormal nonepileptic movements following IM hydroxocobalamin in a patient with TCII deficiency shows a remarkable response to clonazepam.
 
Article
Spina bifida occulta (SBO) is usually considered as benign entity without having any clinical significance. In Pakistan, there is a lack of studies on spina bifida. Clinicians usually ignore the mild urinary complaints and do not look in perspective of SBO background. Micturating cystourethrography (MCUG) of the 71 children with SBO having urinary complaints was done. Analysis was done via SPSS version 20. A total of 70.4% of the patients had urinary tract abnormalities on MCUG. Vesicoureteric reflux was the most common finding. SBO is a clinically significant disorder. Especially in patients with urinary complaints, MCUG must be done to look for underlying pathologies.
 
Article
There is high prevalence rate of attention deficit/hyperactive disorders (ADHD), and there is vague relation between it and epileptiform abnormalities. The objective of this study is to assess the relation between epileptiform abnormalities and ADHD. We studied 50 ADHD children and 25 sex and age matched controls. We used 20 channels electroencephalography under standard condition for assessing patients and control. ADHD rating scale was used for assessing patients. Epileptiform abnormalities were detected in 15 (30%) of ADHD children, in comparison with two (8%) of control group (P < 0.005). While, we did not find any correlation between ADHD subtypes and pattern of epileptiform discharge.
 
Article
An 18-month-old infant who presented with delayed motor development, hypotonia and absent deep tendon reflexes and normal cognitive development was diagnosed to have merosin-positive congenital muscular dystrophy (MP-CMD) on the basis of raised serum levels of creatine kinase, features suggestive of myopathy on electrophysiological studies, dystrophic muscle pathology and normal immunohistochemistry for merosin (laminin-α2). Neuroimaging studies demonstrated white matter hyperintensities on T2-weighted images similar to that seen in patients with merosin negative (MN-CMD). Electrophysiological studies also demonstrated features of axonal involvement. This finding has not been previously described in association with MP-CMD. Although we have not been able to exclude abnormal glycosylation of a-dystroglycan, this case expands the clinical phenotype of MP-CMD and suggests that neuroimaging of children with CMD may be useful in the identification of variants of MP-CMD.
 
Article
The prevalence of motor examination abnormalities among a general pediatric population is unknown. We determined the frequency of motor abnormalities noted at five years of age during a neurologic examination by a child neurologist. As part of a follow-up study of neonatal jaundice in a population of 106,627 births, we randomly selected 419 five-year-old children as healthy controls, of whom 168 consented. Child neurologists blinded to the children's history performed standard neurologic examinations to determine the presence of definite or subtle motor abnormalities. Standardized data on motor and cognitive function were also obtained. Among eight (5%) children diagnosed with a definite motor abnormality, the most common finding was corticospinal tract dysfunction (four unilateral, two bilateral). Two children demonstrated hypotonia and hyporeflexia, one of whom also exhibited proximal weakness. An additional 12 (7%) children were noted to have subtle motor findings that were not clearly abnormal, such as subtle incoordination, mild dystonic posturing, tremor, posting, or hyperreflexia. Children with definite or subtle motor findings were more likely to receive an abnormal score on the Motor Performance Checklist (57% vs. 32%, P = 0.02). There was also a trend towards these children having a lower mean verbal IQ compared to children with normal motor examinations (95.3 vs. 102.1, P = 0.07). Motor examination abnormalities in otherwise healthy 5-year-old children may be more common than previously thought. However, the proportion of children with motor examination abnormalities who have an unrecognized neurologic disorder remains unknown.
 
Article
The frequency and importance of the imaging evaluation of the temporal bone and middle ear have increased significantly over the past 30 years, especially prior to ear surgery. Nowadays, conventional computed tomography (CT) of the temporal bone and in fewer cases magnetic resonance imaging (MRI) of the middle ear allow a detailed evaluation of the small and complex structures of the ear and the surrounding nerves. Familiarity with the spectrum of congenital anomalies of the facial nerve and knowledge of normal facial nerve anatomy lead to simple well-defined diagnostic imaging criteria. The purpose of this article is to discuss the different imaging features of the congenital anomalies of the facial nerve, including agenesia, hypoplasia, anomalies of the course, size, and nerve duplications, compared with normal anatomical images at the same level of section for a better understanding, as the facial nerve must always be analyzed on temporal bone imaging, and any modification of its size or course has to be reported prior to any surgical procedure.
 
Article
The fundamental abnormality in the Sturge-Weber syndrome (SWS) is considered to be the lack of superficial cortical draining veins, which results in numerous collateral pathways of venous flow. Venous abnormalities have been described in detail using angiography but magnetic resonance imaging (MRI) has replaced angiography in the diagnosis of SWS. In this paper we aim to demonstrate the range and evolution of venous abnormalities in the SWS as seen on standard MRI sequences. Retrospective review of 16 MRI scans in a group of ten children with SWS was performed by two pediatric radiologists with emphasis on venous abnormalities. Eight patients had unilateral angiomas and five of these had ipsilateral choroid plexus hypertrophy. Two patients had bilateral angiomas both of which had bilateral choroid plexus hypertrophy. In two patients, the vein of galen was enlarged. Four children had abnormal venous structures including intramedullary veins and enlarged subependymal veins. There was evolution of the venous abnormalities in four of the five cases with follow-up imaging. Three patients had associated cerebral malformations. The predominant venous abnormalities in patients with SWS demonstrated by conventional MRI sequences included anomalous parenchymal veins. Deep venous enlargement as previously described on angiography, was an uncommon finding using MRI. Evolution of venous abnormalities was demonstrated in four of five patients who underwent follow-up examination.
 
Article
The cerebellum abnormalities may be hypoplastic, dysplastic, or hypoplastic. It is very rare that the cerebellar hemisphere is affected unilaterally in the posterior fossa abnormalities. The reason for this effect is mostly sequela. This pathology presents with neuromotor developmental abnormalities. In this presentation, isolated left cerebellar hypoplasia is described radiologically in a 21-month-old male patient with neuromotor development defects. Dysplastic appearance was noticeable in the observable part of the left cerebellar hemisphere and folia. The cerebellar vermis could not be shaped. The right cerebellar hemisphere, other posterior fossa formations, and supratentorial area were natural. In patients with neuromuscular abnormalities, the posterior fossa is applied with care. It should be remembered that cerebellar hypoplasia and dysplasia can be unilateral.
 
Article
Twenty-eight children with tonic clonic seizures and with mean age of 4.6 years received buccal midazolam in a dose of 0.2 mg/kg for control of seizures. Thirteen children were known epilepsy and were on regular antiepileptic treatment, eight had febrile seizures, four had idiopathic first onset seizures, two had meningitis and one hypocalcemia. The seizures were controlled in 64% midazolam and seven patients needed a second dose. These seven patients also received phenytoin/phenobarbitone infusion following the 2nd dose of buccal midazolam. The dose of buccal midazolam was not increased to more than 0.2 mg/kg in any of the patients. Low dose midazolam given by the buccal route is often sufficient to control seizures effectively.
 
Article
Neonatal subgaleal hematomas, rare but potentially fatal accumulations of blood beneath the galea aponeurotica of the scalp, are often associated with instrumental deliveries. We report an unusual case of disseminated intravascular coagulation and massive subgaleal hematoma in a neonate secondary, to placental abruption and disseminated intravascular coagulation in the mother. The neonate presented with subgaleal and subarachnoid hemorrhage and hypovolemic shock soon after birth and developed severe hyperbilirubinemia later on requiring multiple exchange transfusions and aspiration of the hematoma.
 
Article
Orbital abscess following trivial blunt trauma to the eye are uncommon. Few cases are known and reported in the literature. The clinical presentation can be myriad varying from localized presentation to children with marked systemic toxicity. Visual loss is the most dreaded complication and a rapid deterioration in vision may occur if the treatment is delayed. Radiological investigations usually offer a prompt diagnosis but considerable degree of confusion may occur, especially in those cases that lack systemic manifestations of infective pathology. Aggressive medical and surgical treatment is mandatory for a favorable outcome in these cases. We report the case of a child who presented to us with orbital abscess of the left eye following a trivial blunt trauma. No other infective focus was identified. Subsequent imaging revealed abscess of the superior rectus muscle. The child improved following intravenous antibiotics and ultrasonography guided aspiration of the abscess. The clinical and radiological presentation of such cases, management and outcome and a brief review of literature are discussed.
 
Top-cited authors
Martino Ruggieri
  • University of Catania
Andrea Domenico Praticò
  • University of Catania
Richard E Frye
  • The University of Arizona
Piero Pavone
  • University of Catania
Raffaele Falsaperla
  • Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele