Showing papers in "Journal of Child Neurology in 2017"
TL;DR: Cannabidiol is added as a possible treatment for febrile infection-related epilepsy syndrome who had not responded to antiepileptic drugs or other therapies who were given cannabadiol on emergency or expanded investigational protocols in either the acute or chronic phase of illness.
Abstract: Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.
129 citations
TL;DR: This study reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013 and found that children treated with surgical revascularization were less likely to have stroke recurrence.
Abstract: This study aimed to describe children with moyamoya disease from an international multicenter stroke database, and explore risk factors for stroke recurrence. We reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013. A total of 174 children from 32 sites and 14 countries had moyamoya disease; median age 7.4 years, 49% male. Of these, 90% presented with ischemic stroke, 7.5% with transient ischemic attack, and 2.5% with hemorrhagic stroke. One-third of patients had moyamoya syndrome. Stroke recurrence was 20% over median follow-up of 13 months; 9% had multiple recurrences. Children treated with surgical revascularization were less likely to have stroke recurrence ( P = .046). Moyamoya disease accounted for 8% of arterial strokes in this international pediatric stroke registry. One-third of pediatric patients with moyamoya disease have an underlying syndromic condition. Surgical revascularization is effective at reducing the incidence of stroke recurrence.
74 citations
TL;DR: Based on the evidence presented in this review, individuals withFXS and comorbid ASD have more severe behavioral problems than individuals with FXS alone, however, patients with FXs and comerbid ASD exhibit less severe impairments in the social and communication symptoms than patients with nonsyndromic ASD.
Abstract: Fragile X syndrome (FXS) is recognized as the most common genetic cause of intellectual disability and autism spectrum disorder (ASD). Although symptoms of ASD are frequently observed in patients with FXS, researchers have not yet clearly determined whether the symptoms in patients with FXS differ from the symptoms in patients without ASD or nonsyndromic ASD. Behavioral similarities and differences between FXS and ASD are important to improve our understanding of the causes and correlations of ASD with FXS. Based on the evidence presented in this review, individuals with FXS and comorbid ASD have more severe behavioral problems than individuals with FXS alone. However, patients with FXS and comorbid ASD exhibit less severe impairments in the social and communication symptoms than patients with nonsyndromic ASD. Individuals with FXS also present with anxiety and seizures in addition to comorbid ASD symptoms, and differences in these conditions are noted in patients with FXS and ASD. This review also discus...
65 citations
TL;DR: Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate the understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals.
Abstract: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder (incidence 1:33 000-40 000) characterized by formation of central nervous system tumors, due to mutation in the NF2 gene on chromosome 22q12. Vestibular schwannomas are the hallmark lesion, affecting 95% of individuals and typically occur bilaterally. Schwannomas commonly occur on other nerves intracranially and in the spinal compartment, along with meningiomas, ependymomas, and gliomas. Although histologically benign, tumors are associated with significant morbidity due to multiple problems including hearing and vision loss, gait abnormalities, paralysis, pain, and seizures. Risk of early mortality from brainstem compression and other complications is significant. Severity of disease is higher when NF2 presents during childhood. Children have a more variable presentation, which can be associated with significant delays in recognition of the condition. Careful examination of the skin and eyes can identify important clinical signs of NF2 during childhood, allowing timely initiation of disease-specific surveillance and treatment. Monitoring for complications comprises clinical evaluation, along with functional testing including audiology and serial neuroimaging, which together inform decisions regarding treatment. Evidence for disease-specific medical treatment options is increasing, nevertheless most patients will benefit from multimodal treatment including surgery during their lifetime. Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate our understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals.
57 citations
University of Toronto1, University of Alberta2, Alberta Children's Hospital3, University of Western Ontario4, Children's Hospital of Eastern Ontario5, McMaster Children's Hospital6, University of British Columbia7, McMaster University8, Public Health Agency of Canada9, University of Manitoba10, McGill University11, Montreal Children's Hospital12
TL;DR: Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.
Abstract: We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.
45 citations
TL;DR: This review aims to summarize the risk of anesthesia in children with an emphasis on anesthetic-related neurotoxicity, acknowledge the value of pediatric neuroimaging, and address this call for conversation.
Abstract: Each year millions of young children undergo procedures requiring sedation or general anesthesia. An increasing proportion of the anesthetics used are provided to optimize diagnostic imaging studies such as magnetic resonance imaging. Concern regarding the neurotoxicity of sedatives and anesthetics has prompted the US Food and Drug Administration to change labeling of anesthetics and sedative agents warning against repeated or prolonged exposure in young children. This review aims to summarize the risk of anesthesia in children with an emphasis on anesthetic-related neurotoxicity, acknowledge the value of pediatric neuroimaging, and address this call for conversation.
44 citations
TL;DR: Clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis are supported.
Abstract: Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.
43 citations
TL;DR: Neonatal brain MRI provides prognostic information on outcome beyond early infancy in hypoxic-ischemic encephalopathy and therapeutic hypothermia does not change its prognostic value.
Abstract: Objective:To quantify the prognostic value of neonatal brain magnetic resonance imaging (MRI) in neonatal hypoxic-ischemic encephalopathy.Methods:Meta-analysis of studies with ≥35-week neonates wit...
40 citations
TL;DR: The authors present 2 pediatric cases of reversible cerebral vasoconstriction syndrome and review the previous 11 pediatric cases in the literature, finding that the clinical and radiographic features are similar in both pediatric and adult cases.
Abstract: Reversible cerebral vasoconstriction syndrome is a transient vasculopathy associated with severe headaches and stroke. In most cases of reversible cerebral vasoconstriction syndrome, there is a precipitating event or trigger, such as pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2 pediatric cases of reversible cerebral vasoconstriction syndrome and review the previous 11 pediatric cases in the literature. In many instances, the clinical and radiographic features are similar in both pediatric and adult cases. In the pediatric group, reported potential triggers include trauma (1/13), exercise (2/13), water to the face (3/13), hypertension (3/13), and medication or substance use (4/13). One surprising difference is that 11 out of 13 pediatric patients with reversible cerebral vasoconstriction syndrome are male while most cases in adults are female. Many of the pediatric patients with reversible cerebral vasoconstriction syndrome were treated with a calcium channel blocker and the overall outcome of pediatric reversible cerebral vasoconstriction syndrome was good, with most patients experiencing a full recovery.
37 citations
TL;DR: Epileptic Encephalopathy was selected as the topic for the 15th Neurobiology of Disease in Children conference, which was held in Washington, DC, on October 7-8, 2015 and featured individual presentations, question-and-answer sessions, and a future directions panel discussion with highly respected leaders in the field of epileptic encephalopathy.
Abstract: Epileptic Encephalopathy was selected as the topic for the 15th Neurobiology of Disease in Children (NDC) conference, which was held in Washington, DC, on October 7-8, 2015. Program directors Drs Tallie Z. Baram and Shlomo Shinnar prepared an outstanding agenda that included individual presentations, question-and-answer sessions, and a future directions panel discussion with highly respected leaders in the field of epileptic encephalopathy. In the first session, Clinical Aspects, Dr Susan Koh discussed the most salient clinical presentations as well as electroencephalographic (EEG) findings, both interictally and during a seizure. Although EEG patterns in West syndrome vary considerably from patient to patient, different hypsarrhythmia patterns do not have prognostic significance. Between 60% and 70% of patients have a known etiology, including an array of genetic and metabolic causes. Dr Koh discussed treatment options; high-dose adrenocorticotropic hormone seems to be preferred as first-line treatment by most child neurologists. Many children with infantile spasms transition to LennoxGastaut syndrome, as discussed next by Dr Jim Wheless. However, only a small proportion (10% to 20%) of children with Lennox-Gastaut syndrome have had prior West syndrome. Dr Wheless discussed findings of neuroimaging studies showing how epileptiform discharges recruit widespread areas of association cortex. Genetic studies show positive findings in 10% to 15% of cases and 80% of patients continue to have epilepsy as adults. Dr Edouard Hirsch discussed electrical status epilepticus in sleep/Landau-Kleffner syndrome, including genetic and immune hypotheses. Dr Angela Vincent reviewed the autoimmune encephalopathies. Gray matter antibody diseases in children include voltage-gated potassium channels-complexantibodies with autoimmune encephalitis, N-methyl-D-aspartate receptor antibody encephalitis, glycine receptor-antibody encephalomyelitis, and g-aminobutyric acid A receptorantibody encephalitis. Encephalopathy, seizures, and cognitive and behavioral changes are common presentations of immune encephalopathies, and children are usually afebrile at presentation. The second session on Molecular Features and Pathogenesis started with a presentation by Dr Greg Holmes on vulnerability of the developing brain and potential causes of cognitive dysfunction in epileptic encephalopathy. Dr Sookyong Koh then discussed neuroinflammation, noting that immune cells have been detected in the brains of patients with refractory epilepsy and steroids have been used as anti-inflammatory treatment, with a subsequent anticonvulsant effect. She showed how there is a nonlinear, amplifying feedback loop of crosstalk between innate and adaptive immunity. The microglial activation leads to infiltration of professional antigen-presenting cells, which then cause T-cell infiltration. Some of the T cells, gamma delta T cells, function as both innate and adaptive immunity, and thus neuroinflammation predisposes, precipitates, and perpetuates epileptogenesis. In light of these findings, Dr Tallie Baram discussed potential therapeutic targets. Dr Baram showed that in epileptic encephalopathy, insults can be genetic, acquired, or both, and they have secondary results on neurons, including killing them or impairing synaptic plasticity, which will influence the neuronal network. Many different kinds of insults also change the property of neurons through large-scale epigenetic changes, and these persist. These may be associated with altered metabolism, ongoing seizures, or neurons functioning inefficiently because channels or other molecules are wrong, and this will create an augmented demand without sufficient supply. Additionally, there also may be changes in the glia that influence neurons in many different ways through metabolism, through inflammation, and through impaired synaptic function. All these together coalesce to result in abnormal function of neuronal networks, manifesting as ongoing seizures that have their own side effects as well as cognitive problems, and this results in epileptic encephalopathy. In session 3, Therapeutic Targets and Translational Opportunities, Dr Shlomo Shinnar reviewed the current state of the art on therapy. Dr Shinnar showed that in randomized controlled trials, high-dose adrenocorticotropic hormone has consistently been superior for infantile spasms and that treatment within the first month of seizure onset has a higher response
37 citations
TL;DR: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years.
Abstract: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. Diagnosis was most often set in 12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years.
TL;DR: Children with idiopathic intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.
Abstract: Magnetic resonance imaging (MRI) signs of elevated intracranial pressure and idiopathic intracranial hypertension have been well characterized in adults but not in children. The MRIs of 50 children with idiopathic intracranial hypertension and 46 adults with idiopathic intracranial hypertension were reviewed for optic nerve head protrusion, optic nerve head enhancement, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, empty or partially empty sella, tonsillar herniation, enlargement of Meckel's cave meningoceles, and transverse venous sinus stenosis(TSS). Compared to adolescents (11-17 years, n = 40) and adults (>17 years, n = 46), prepubescent children (<11 years, n = 10) had lower frequencies of scleral flattening (50% vs 89% and 85%, P = .02), increased perioptic cerebrospinal fluid (60% vs 84% and 89%, P = .08), optic nerve tortuosity (20% vs 46% and 59%, P = .07), empty or partially empty sella (56% vs 78% and 93%, P = .007), and TSS (67% vs 93% and 96%, P = .04). Children with idiopathic intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.
TL;DR: The authors suggest that elevated blood pressure may be a significant risk factor that, alone or in combination with other multiple risk factors, leads to the development of stroke in childhood and recommend that blood pressure be measured and assessed carefully in every child presenting with acute stroke.
Abstract: Hypertension is the single most important modifiable risk factor for adult stroke. Stroke mortality has significantly decreased over the last 5 decades; this decline has been mainly associated to improved blood pressure control. Though much less prevalent than in adults, stroke is an increasingly recognized cause of morbidity and mortality in children. Although hypertension has not been strongly identified as a risk factor in childhood stroke yet, there is preliminary evidence that suggests that elevated blood pressure may be associated with stroke in children. This review summarizes the literature that may link elevated blood pressure to the development of childhood ischemic and hemorrhagic stroke. The authors suggest that elevated blood pressure may be a significant risk factor that, alone or in combination with other multiple risk factors, leads to the development of stroke in childhood. It is therefore recommend that blood pressure be measured and assessed carefully in every child presenting with acute stroke.
TL;DR: It is confirmed that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects, and age was positively and significantly associated with the Cerebellar volumes.
Abstract: Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm3 vs.138.90±15.32 cm3). The effect was present in both females and males (males 136.9±14.37 cm3 vs. 141.20±14.75 cm3; females 125.7±12.34 cm3 vs. 131.20±15.03 cm3). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.
TL;DR: Amplitude-integrated EEG had an 86% sensitivity for detection of babies with seizures; however, it was nonspecific, in that 50% of infants with seizures detected by amplitude- integrated EEG did not have true seizures by video EEG.
Abstract: This diagnostic accuracy study compared the accuracy of seizure detection by amplitude-integrated electroencephalography with the criterion standard conventional video EEG in term and near-term infants at risk of seizures. Simultaneous recording of amplitude-integrated EEG (2-channel amplitude-integrated EEG with raw trace) and video EEG was done for 24 hours for each infant. Amplitude-integrated EEG was interpreted by a neonatologist; video EEG was interpreted by a neurologist independently. Thirty-five infants were included in the analysis. In the 7 infants with seizures on video EEG, there were 169 seizure episodes on video EEG, of which only 57 were identified by amplitude-integrated EEG. Amplitude-integrated EEG had a sensitivity of 33.7% for individual seizure detection. Amplitude-integrated EEG had an 86% sensitivity for detection of babies with seizures; however, it was nonspecific, in that 50% of infants with seizures detected by amplitude-integrated EEG did not have true seizures by video EEG. In conclusion, our study suggests that amplitude-integrated EEG is a poor screening tool for neonatal seizures.
TL;DR: Long-term follow-up allowed us to define additional indicators: syndromic agenesis of corpus callosum plus patients showed the most severe clinical features while isolated complete agenetic patients had the mildest symptoms, although they observed intellectual disability and epilepsy in both categories.
Abstract: To gain a better understanding of the clinical and genetic features associated with agenesis of corpus callosum, we enrolled and characterized 162 patients with complete or partial agenesis of corpus callosum. Clinical and genetic protocols allowed us to categorize patients as syndromic subjects, affected by complex extra-brain malformations, and nonsyndromic subjects without any additional anomalies. We observed slight differences in sex ratio (56% males) and agenesis type (52% complete). Syndromic agenesis of corpus callosum subjects were prevalent (69%). We detected associated cerebral malformations in 48% of patients. Neuromotor impairment, cognitive and language disorders, and epilepsy were frequently present, regardless of the agenesis of corpus callosum subtype. Long-term follow-up allowed us to define additional indicators: syndromic agenesis of corpus callosum plus patients showed the most severe clinical features while isolated complete agenesis of corpus callosum patients had the mildest symptoms, although we observed intellectual disability (64%) and epilepsy (15%) in both categories. We achieved a definitive (clinical and/or genetic) diagnosis in 42% of subjects.
TL;DR: Children with anti-NDMAR encephalitis may have long-term effects impacting daily life while adults regain normal function.
Abstract: This study compared neurologic disability and adaptive function in children and adults >1 year following anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis diagnosis. Retrospective record review identified 12 patients with anti-NMDAR encephalitis. At last follow-up, all surviving patients had "good" modified Rankin Score (0-2). Four children, 6 adults, and their families participated in a telephone interview. Median duration since diagnosis was similar for children (2.42 years, interquartile range 2.12-3.32) and adults (3.55 years, interquartile range 2.08-5.50 years). 3/4 (75%) pediatric and 3/5 (60%) adult patients reported neuropsychiatric symptoms (fatigue, emotional lability, short-term memory deficits or concentration deficits). On the Adaptive Behavior Assessment System (ABAS-3), although overall adaptive function was intact for adults (general adaptive composite standard score: median 104.5, interquartile range 98.8-112.5), the median for children was below average (General Adaptive Composite Standard Score: median 82.0, interquartile range 79.0-89.0). Children with anti-NDMAR encephalitis may have long-term effects impacting daily life while adults regain normal function.
TL;DR: The first disease-specific scale for the quantitative assessment of health-related quality of life in 118 children and adolescents with Gilles de la Tourette syndrome (C&A-GTS-QOL) following language adaptation from Italian to English in the United Kingdom is validated.
Abstract: Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder that can have a detrimental impact on the health-related quality of life of children with the condition. To date no patient-reported health-related quality of life measures have been developed for children and adolescents in the English language. This study validated the first disease-specific scale for the quantitative assessment of health-related quality of life in 118 children and adolescents with Gilles de la Tourette syndrome (CA validity was supported by interscale correlations (range 0.2-0.7), confirmatory factor analysis, and correlation patterns with other rating scales and clinical variables.
TL;DR: SOD is clinically and radiologically heterogeneous, and cortical abnormalities are very common, and neurodevelopmental deficits are very prevalent, and of wide-ranging severity.
Abstract: We retrospectively reviewed the clinical and radiologic characteristics of 17 individuals with septo-optic dysplasia (SOD) and attempted to identify correlations between imaging findings, clinical features, and neurodevelopmental outcome. Surprisingly, only 1 (6%) individual was classified as classic SOD (with septum pellucidum/corpus callosum dysgenesis), 3 (18%) as SOD-like (with normal septum pellucidum/corpus callosum) and the majority, 13 (76%), as SOD-plus (with cortical brain malformation). Cortical abnormalities included schizencephaly, polymicrogyria, and gray matter heterotopias. All individuals had optic nerve hypoplasia, 11 (65%) had endocrinologic deficits, and 13 (76%) had abnormal cerebral midlines. Seven individuals (41%) had all 3 features. Neurodevelopmental outcome was abnormal in 13 (78%), ranging from mild to severe developmental delay. Individuals with SOD-plus did not have more severe neurologic deficits than individuals with classic or SOD-like subgroups. Thus, SOD is clinically and radiologically heterogeneous, and cortical abnormalities are very common. Neurodevelopmental deficits are very prevalent, and of wide-ranging severity.
TL;DR: A 2-year-old boy with severe head trauma was diagnosed brain dead according to the 2011 Pediatric Guidelines; a few minutes after withdrawal of support, the boy began to breathe spontaneously, so the ventilator was immediately reconnected and the death declaration rescinded.
Abstract: A 2-year-old boy with severe head trauma was diagnosed brain dead according to the 2011 Pediatric Guidelines. Computed tomographic (CT) scan showed massive cerebral edema with herniation. Intracranial pressures were extremely high, with cerebral perfusion pressures around 0 for several hours. An apnea test was initially contraindicated; later, one had to be terminated due to oxygen desaturation when the Pco2 had risen to 57.9 mm Hg. An electroencephalogram (EEG) was probably isoelectric but formally interpreted as equivocal. Tc-99m diethylene-triamine-pentaacetate (DTPA) scintigraphy showed no intracranial blood flow, so brain death was declared. Parents declined organ donation. A few minutes after withdrawal of support, the boy began to breathe spontaneously, so the ventilator was immediately reconnected and the death declaration rescinded. Two hours later, life support was again removed, this time for prognostic reasons; he did not breathe, and death was declared on circulatory-respiratory grounds. Implications regarding the specificity of the guidelines are discussed.
TL;DR: It is found that levetiracetam is an efficacious medication in treatment of seizures in the setting of neonatal hypoxic ischemic encephalopathy and future prospective studies should explore its use as a first-line medication.
Abstract: The objective of this study was to determine the efficacy and safety of levetiracetam in treatment of neonatal seizures due to hypoxic ischemic encephalopathy. Seizures often persist in neonates with hypoxic ischemic encephalopathy despite phenobarbital. A retrospective single-center study was conducted in neonates ≥36 weeks gestation with hypoxic ischemic encephalopathy. A total of 127 neonates were identified born 2008-2015. Clinical seizures occurred in 83 infants. Fifty-one neonates (61%) had cessation of seizures with only phenobarbital. Thirty-two neonates received levetiracetam after phenobarbital, and the seizures stopped in 27 of these neonates. The mean total loading dose of levetiracetam was 63 mg/kg. Mean maintenance dose of levetiracetam was 65 mg/kg/d. We found no negative side effects in neonates following levetiracetam use. Our study finds that levetiracetam is an efficacious medication in treatment of seizures in the setting of neonatal hypoxic ischemic encephalopathy. Future prospective studies should explore its use as a first-line medication.
TL;DR: History of previous hip surgery, intractable epilepsy, and female gender are predictors of developing severe scoliosis in children with cerebral palsy, and this knowledge should aid in the early diagnosis of scolia and timely referral to specialist services.
Abstract: This study aims to identify the risk factors leading to the development of severe scoliosis among children with cerebral palsy. A cross-sectional descriptive study of 70 children (aged 12-18 years) with severe spastic and/or dystonic cerebral palsy treated in a single specialist unit is described. Statistical analysis included Fisher exact test and logistic regression analysis to identify risk factors. Severe scoliosis is more likely to occur in patients with intractable epilepsy ( P = .008), poor gross motor functional assessment scores ( P = .018), limb spasticity ( P = .045), a history of previous hip surgery ( P = .048), and nonambulatory patients ( P = .013). Logistic regression model confirms the major risk factors are previous hip surgery ( P = .001), moderate to severe epilepsy ( P = .007), and female gender ( P = .03). History of previous hip surgery, intractable epilepsy, and female gender are predictors of developing severe scoliosis in children with cerebral palsy. This knowledge should aid in the early diagnosis of scoliosis and timely referral to specialist services.
TL;DR: The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain, and there was no evidence of a cumulative effect on adverse events.
Abstract: This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ≥1 open label injection into the gastrocnemius-soleus; 17-24% of patients also had injections into the hamstrings. The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain (n = 10). There was no evidence of a cumulative effect on adverse events. Sustained significant clinical improvements in muscle tone (Modified Ashworth Scale), spasticity (Tardieu Scale), overall clinical benefit (Physicians Global Assessment), and goal attainment (Goal Attainment Scale) were also observed across treatment cycles.
TL;DR: Primary data from parents can serve as a useful framework to guide the development and interpretation of parent-centered outcomes and offer insight into the lived experience of parenting an infant with neonatal encephalopathy.
Abstract: We aimed to characterize the parent experience of caring for an infant with neonatal encephalopathy. In this mixed-methods study, we performed semistructured interviews with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. Thematic saturation was achieved after 20 interviews. Parent experience of caring for a child with neonatal encephalopathy was characterized by 3 principal themes. Theme 1: Many families described cumulative loss and grief throughout the perinatal crisis, critical neonatal course, and subsequent missed developmental milestones. Theme 2: Families experienced entangled infant and broader family interests. Theme 3: Parents evolved into and found meaning in their role as an advocate. These data offer insight into the lived experience of parenting an infant with neonatal encephalopathy. Primary data from parents can serve as a useful framework to guide the development and interpretation of parent-centered outcomes.
TL;DR: Corpus callosotomy is an effective treatment for intractable generalized epilepsy leading to falls with significant seizure reduction or even elimination of seizures, in the majority of children.
Abstract: Corpus callosotomy is a palliative procedure performed to reduce the severity of drug-resistant epilepsy. The authors assessed its efficacy on different seizure types in 20 subjects (age range 5-19 years); 8 with active vagus nerve stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had anterior 2/3 followed later by complete callosotomy. Ten had endoscopic approach. In all, 65% had ≥ 50% reduction of generalized seizures leading to falls (atonic, tonic, myoclonic); 35% became seizure-free (follow-up period: 6 months to 9 years; mean 3 years). Seizure outcome distribution was better for generalized than for partial seizures ( P = .003). Endoscopic approach was as effective as transcranial approach. Seven subjects who failed vagus nerve stimulator therapy responded with ≥50% seizure reduction. Corpus callosotomy is an effective treatment for intractable generalized epilepsy leading to falls with significant seizure reduction or even elimination of seizures, in the majority of children.
TL;DR: Poor motor outcomes were associated with lower fractional anisotropy in all segments and radial diffusivity correlated with both Assisting Hand Assessment and Melbourne Assessment, and correlations with disability support clinical relevance and utility in model development for personalized rehabilitation.
Abstract: Perinatal stroke injures developing motor systems, resulting in hemiparetic cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We used diffusion tensor imaging to assess ...
TL;DR: Proton magnetic resonance spectroscopy was used to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in autism spectrum disorder and found ASD subjects have hypoGABAergic alterations in the posterior cingulated cortex and hyperglutamatergic/hypo GABAergic alteration in the left Cerebellum.
Abstract: The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.
TL;DR: It is suggested that greater microstructural white matter integrity of the corona radiata is partly associated with attention across 4 attention dimensions, and that white matter microstructure of the Corona Radata is a neural correlate of several, but not all, attention dimensions.
Abstract: Mirsky proposed a model of attention that included these dimensions: focus/execute, sustain, stabilize, encode, and shift. The neural correlates of these dimensions were investigated within corona radiata subregions in healthy youth. Diffusion tensor imaging and neuropsychological assessments were conducted in 79 healthy, right-handed youth aged 4-17 years. Diffusion tensor imaging maps were analyzed using standardized parcellation methods. Partial Pearson correlations between neuropsychological standardized scores, representing these attention dimensions, and diffusion tensor imaging measures of corona radiata subregions were calculated after adjusting for gender and IQ. Significant correlations were found between the focus/execute, sustain, stabilize, and shift dimensions and imaging metrics in hypothesized corona radiata subregions. Results suggest that greater microstructural white matter integrity of the corona radiata is partly associated with attention across 4 attention dimensions. Findings suggest that white matter microstructure of the corona radiata is a neural correlate of several, but not all, attention dimensions.
TL;DR: There is no conclusive evidence supporting a causal relationship between the human papillomavirus vaccine and POTS, and it is of utmost importance to recognize that while temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population.
Abstract: The human papillomavirus (HPV) vaccine is efficacious in preventing complications of human papillomavirus infection including cervical cancer. However, there have been case reports of adverse events occurring after vaccination, one being postural orthostatic tachycardia syndrome (POTS). This article reviews published data and other available information regarding the relationship between the human papillomavirus vaccine and POTS. Background information is provided regarding the human papillomavirus vaccine and the proposed post-vaccination adverse event POTS. Peer-reviewed literature, statements by government and medical advisory committees, and publicly available information published on this topic are examined. At this time, there is no conclusive evidence supporting a causal relationship between the human papillomavirus vaccine and POTS. Though a causal relationship has been postulated, it is of utmost importance to recognize that while temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population.
TL;DR: An anonymous survey sent to members of the Child Neurology Society is designed to identify the current practices among child neurologists and highlight areas of practice uniformity, including first-line treatment with intravenous immunoglobulin and intravenous methylprednisone and initiation of disease-modifying therapy with rituximab alone.
Abstract: Anti–N-methyl-d-aspartate receptor (NMDAR) encephalitis has been shown to be a treatable form of autoimmune encephalitis, but there remains no standardized approach to immunotherapy. We designed an anonymous survey sent to members of the Child Neurology Society to identify the current practices among child neurologists. A total of 151 pediatric neurologists responded to the survey. With these responses we were able to highlight areas of practice uniformity, including first-line treatment with intravenous immunoglobulin and intravenous methylprednisone and initiation of disease-modifying therapy with rituximab alone. The survey also identifies existing gaps in knowledge, specifically, when to add disease-modifying therapy and how long to continue therapy. We propose that the areas of agreement can be used as a step toward establishing standard treatment guidelines and research protocols directed at evidence-based clinical trials.