Neurocutaneous Disorders in Pregnancy.

Importance: Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective: This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition: A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms "pregnancy," "Sturge -Weber," "Neurofibromatosis Type 1," "neurofibromatosis type 2," "von Hippel Lindau," "Tuberous Sclerosis," "neurocutaneous disorder," "treatment," "congenital malformations," "neurodevelopmental defects," "miscarriage," "breastfeeding," "autoimmune," "pathophysiology," and "management." References of included articles were searched to identify any articles that may have been missed after the above method was used. Results: Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance: Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients.

Yield of Neurodiagnostic Testing in Children Presenting to a Pediatric Emergency Department With Altered Mental Status.

BACKGROUND: Emergency department (ED) visits for altered mental status (AMS) in children are common. Neuroimaging is often performed to ascertain etiology, but its utility has not been well studied. Our objective is to describe the yield of neuroimaging studies in children who present to an ED with AMS. METHODS: We performed a retrospective chart review of children 0-18 years of age, presenting to our PED between 2018 and 2021 with AMS. We abstracted patient demographics, physical examination, neuroimaging and EEG results, and final diagnosis. Neuroimaging and EEG studies were classified as normal or abnormal. Abnormal studies were categorized as clinically important and contributory: abnormalities that were clinically important and contributed to the etiology, clinically important but noncontributory: abnormalities that were clinically significant but did not explain the etiology, and incidental: abnormalities that were not clinically significant. RESULTS: We analyzed 371 patients. The most common etiology of AMS was toxicologic (188, 51%) with neurologic causes (n = 50, 13.5%) accounting for a minority. Neuroimaging was performed in one-half (169, 45.5%) and abnormalities were noted in 44 (26%) studies. Abnormalities were clinically important and contributed to the etiologic diagnosis of AMS in 15/169 (8.9%), clinically important and noncontributory in 18/169 (10.7%), and incidental in 11/169 (6.5%). EEG was performed in 65 patients (17.5%), of which 17 (26%) were abnormal with only one being clinically important and contributory. CONCLUSIONS: Though neuroimaging was performed in approximately one half of the cohort, it was contributory in a minority. Similarly, diagnostic utility of EEG in children with AMS was low.

Artificial Intelligence and the detection of pediatric concussion using epigenomic analysis.

Concussion, also referred to as mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury. Currently concussion is an area ofintensescientific interest to better understand the biological mechanisms and for biomarker development. We evaluated whole genome-wide blood DNA cytosine ('CpG') methylation in 17 pediatric concussion isolated cases and 18 unaffected controls using Illumina Infinium MethylationEPIC assay. Pathway analysis was performed using Ingenuity Pathway Analysis to help elucidate the epigenetic and molecular mechanisms of the disorder. Area under the receiver operating characteristics (AUC) curves and FDR p-values were calculated for mTBI detection based on CpG methylation levels. Multiple Artificial Intelligence (AI) platforms including Deep Learning (DL), the newest form of AI, were used to predict concussion based on i) CpG methylation markers alone, and ii) combined epigenetic, clinical and demographic predictors. We found 449 CpG sites (473 genes), those were statistically significantly methylated in mTBI compared to controls. There were four CpGs with excellent individual accuracy (AUC ≥ 0.90-1.00) while 119 displayed good accuracy (AUC ≥ 0.80-0.89) for the prediction of mTBI. The CpG methylation changes ≥10% were observed in many CpG loci after concussion suggesting biological significance. Pathway analysis identified several biologically important neurological pathways that were perturbed including those associated with: impaired brain function, cognition, memory, neurotransmission, intellectual disability and behavioral change and associated disorders. The combination of epigenomic and clinical predictors were highly accurate for the detection of concusion using AI techniques. Using DL/AI, a combination of epigenomic and clinical markers had sensitivity and specificity ≧95% for prediction of mTBI. In this novel study, we identified significant methylation changes in multiple genes in response to mTBI. Gene pathways that were epigenetically dysregulated included several known to be involved in neurological function, thus giving biological plausibility to our findings.

Risk factors and motor outcome of paediatric stroke patients.

BACKGROUND: Childhood stroke causes significant morbidity and mortality. In this study, we aimed to define the presenting findings, causes, risk factors and motor outcomes of our patients. METHODS: We retrospectively analysed patients aged from 1 month to 18 years who were diagnosed as having the first onset of stroke between January 2006 and December 2015. Presenting features, causes, risk factors, recurrence rate and motor outcomes were recorded. Motor outcome was evaluated by the gross motor function classification system. RESULTS: Forty-seven children were included in the study. Thirty-eight (78.7%) children had an arterial stroke, 9 (19.1%) had a venous stroke. The median age at the time of presentation was 60 months (3-214). Thirty-two patients (68%) presented with a focal neurological sign and 9 presented with seizure (19.1%). Patients who had a venous stroke presented with more diffuse neurological symptoms than those who had an arterial stroke. At least one risk factor for stroke was identified in 74.5% of the patients; the most common causative factor was prothrombotic state seen in 16 patients (33.5%). Stroke recurred in 5 patients (10.6%); coexistence of multiple factors was a risk factor for recurrence. Presenting with seizure was not a facilitator for epilepsy. Thirty-two (68%) patients had a favourable motor outcome. Younger age (24 months versus 114 months) and presenting with focal neurological signs were related to non-favourable motor outcome. CONCLUSION: Our cohort demonstrates that most of the children had a risk factor for stroke and have had favourable motor outcome. However, younger age and presenting with focal seizures are related to non-favourable motor outcome.

Identification of a New de Novo Mutation Underlying Regressive Episodic Ataxia Type I.

Episodic ataxia type 1 (EA1), a Shaker-like K+channelopathy, is a consequence of genetic anomalies in the KCNA1 gene that lead to dysfunctions in the voltage-gated K+ channel Kv1. 1. Generally, KCNA1 mutations are inherited in an autosomal dominant manner. Here we report the clinical phenotype of an EA1 patient characterized by ataxia attacks that decrease in frequency with age, and eventually leading to therapy discontinuation. A new de novo mutation (c.932G>A) that changed a highly conserved glycine residue into an aspartate (p.G311D) was identified by using targeted next-generation sequencing. The conserved glycine is located in the S4-S5 linker, a crucial domain controlling Kv1.1 channel gating. In silico analyses predicted the mutation deleterious. Heterologous expression of the mutant (Kv1.1-G311D) channels resulted in remarkably decreased amplitudes of measured current, confirming the identified variant is pathogenic. Collectively, these findings corroborate the notion that EA1 also results from de novo variants and point out that regardless of the mutation-induced deleterious loss of Kv1.1 channel function the ataxia phenotype may improve spontaneously.

Guillain-Barré syndrome in children: subtypes and outcome.

OBJECTIVE: This study reviews the clinical features, subtypes, and outcomes of childhood Guillain-Barré syndrome (GBS). METHODS: Fifty-four children who attended a tertiary care training and research hospital in Turkey were enrolled in the study. RESULTS: The mean age was 6.5 ± 4.2 years and 32 patients (59.5%) were male. The most common subtype of GBS was acute inflammatory demyelinating polyneuropathy (AIDP), which was seen in 27 patients (50%). Having antecedent history, especially upper respiratory tract infection was significantly more common in AIDP (P = 0.028). Sensorial symptoms were significantly more frequent in axonal type GBS (P = 0.001). When we compare the demyelinating and axonal forms, all of the groups had favorable outcome. CONCLUSION: The diagnosis of pediatric GBS can be delayed because of its variable presentation. Early admission to hospital and early treatment are important for decreasing the need for respiratory support and improving the outcome.

Childhood peripheral facial palsy.

OBJECTIVE: The objectives of this study were to evaluate the demographic and clinical characteristics, causes, treatment patterns, outcome, and recurrence of childhood peripheral facial palsy. METHODS: We performed a retrospective study of 144 peripheral facial palsy patients, under 18 years old in a tertiary care pediatric hospital. Medical charts were reviewed to analyze the age, gender, side of facial nerve paralysis, family history, cause, grading by the House-Brackmann Facial Nerve Grading Scale (HBS), results of diagnostic tests, therapies, outcomes, and recurrence. RESULTS: Causes were as follows: 115 idiopathic (Bell's palsy) facial palsy (79.9%), 17 infections (11.8%) (9 otitis media, 4 varicella zoster virus (VZV) infection, 3 tooth abscess, and 1 group A ß-hemolytic streptococcus infection), 7 trauma (4.9%), 4 congenital-syndrome (2.8%), and 1 (0.7%) arterial hypertension. There was no difference in age, sex, family history, grading, or outcome between idiopathic and cause-defined facial palsy. At the end of the first year, our recovery rates were 98.3%. No significant difference in recovery outcome was detected between the patients who were treated with and without steroid treatment. Thirteen (9%) patients had recurrent attacks, and no differences in the outcomes of patients with recurrent facial palsy were observed. Recurrence time ranged from 6 months to 6 years. CONCLUSION: The results of this study indicate that both Bell's palsy and cause-defined facial palsy in children have a very good prognosis. Medical treatment based on corticosteroids is not certainly effective in improving outcomes in children. Recurrent attacks occurred in 6 years from the onset which leads to the conclusion that we should have a long-term follow-up of patients diagnosed with Bell's palsy.

Brain magnetic resonance imaging findings in children with headache. / Resultados de la resonancia magnética nuclear de cerebro en niños con cefalea.

INTRODUCTION: The aim was to describe the findings on magnetic resonance imaging (MRI) in children with headache. POPULATION AND METHODS: Retrospective review of the medical records of patients who were admitted to our pediatric outpatient neurology clinics with the complaint of headache between January 2013 and December 2014. RESULTS: A total of 478 patients (273 female, 205 male) were admitted with the complaint of headache. The types of headache were migraine in 218 (45.6%), tension-type in 159 (33.3%), secondary in 39 (8.2%) and unspecified headaches in 62 (13%) patients. Brain MRI was performed in 407 (85%) patients and revealed cerebral abnormalities in 128 (31.4%) patients; 5 patients had cerebral abnormalities relevant with headache, including tumors. Amongst the others 123 patients, the most common findings were 42 cases (10%) of nonspecific white matter abnormalities, 17 cases (4%) of enlarged perivascular spaces, 17 cases (4%) of arachnoid cyst, 16 cases (3.9%) of asymmetric ventricles, 12 cases (2.9%) with Chiari type I and cerebellar tonsillar ectopia. Also, 17 (4.1%) patients had extra-cerebral MRI abnormalities including sinusitis, mucosal thickening and retention cysts of sinuses. CONCLUSIONS: In this study, the contribution of brain MRI in the diagnosis and management of the children with headache was still low.

INTRODUCCIÓN: El objetivo fue describir los resultados de la resonancia magnética nuclear (RMN) en niños con cefalea. POBLACIÓN Y MÉTODOS: Revisión retrospectiva de las historias clínicas de los pacientes ingresados a los consultorios externos de neurología pediátrica con síntomas de cefalea entre enero de 2013 y diciembre de 2014. RESULTADOS: Se ingresaron 478 pacientes (273 mujeres, 205 varones) con síntomas de cefalea. Los tipos de cefalea fueron migraña en 218 pacientes (45,6%), cefalea tensional en 159 (33,3%), cefalea secundaria en 39 (8,2%) y cefalea inespecífica en 62 (13%). Se realizó una RMN de cerebro a 407 pacientes (85%); se observaron anomalías cerebrales en 128 pacientes (31,4%); cinco tenían anomalías cerebrales relevantes para cefalea, incluso tumores. Entre los otros 123 pacientes, los hallazgos casuales más frecuentes correspondieron a 42 casos (10%) de anomalías inespecíficas de la sustancia blanca, 17 casos (4%) de espacios perivasculares agrandados, 17 casos (4%) de quiste aracnoideo, 16 casos (3,9%) de ventrículos asimétricos, 12 casos (2,9%) de malformación de Chiari tipo 1 y ectopia amigdalina cerebelosa. Asimismo, 17 pacientes (4,1%) tenían anomalías extracerebrales en la RMN, entre otras, sinusitis, engrosamiento de la mucosa y quistes de retención de los senos paranasales. CONCLUSIONES: A pesar del incremento en la realización de estudios de neuroimagenología, la contribución de la RMN de cerebro al diagnóstico y el tratamiento de los niños con cefalea es aún baja.

Epilepsy surgery for epileptic encephalopathy as a sequela of herpes simplex encephalitis: case report.

Herpes simplex virus (HSV) encephalitis can manifest with different clinical presentations, including acute monophasic illness and biphasic chronic granulomatous HSV encephalitis. Chronic encephalitis is much less common, and very rare late relapses are associated with intractable epilepsy and progressive neurological deficits with or without evidence of HSV in the cerebrospinal fluid. The authors report on an 8-year-old girl with a history of treated HSV-1 encephalitis when she was 13 months of age and focal epilepsy when she was 2 years old. Although free of clinical seizures, when she was 5, she experienced behavioral and academic dysfunction, which was later attributed to electrographic focal seizures and worsening electroencephalography (EEG) findings with electrical status epilepticus during slow-wave sleep (ESES). Following a right temporal lobectomy, chronic granulomatous encephalitis was diagnosed. The patient's clinical course improved with the resolution of seizures and EEG abnormalities.

Susac's Syndrome (Retinocochleocerebral Vasculopathy): Follow-up of a Pediatric Patient.

Susac's syndrome (SS) is a triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensorineural hearing loss as a result of microvascular occlusions of the brain, retina, and inner ear. It is also a disorder of autoimmune endotheliopathy. SS usually affects young women between the age of 20 and 40 years. SS can be misdiagnosed as multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM) because of similar findings. A 15-year-old girl presented in June 2015 with vomiting and severe headache. Cerebral magnetic resonance imaging revealed multiple lesions in the corpus callosum. Cerebrospinal fluid findings gave normal results. The initial diagnosis was MS and steroid (1000 mg/day) was given. She started to describe hallucinations and became paraplegic. She then underwent plasmapheresis five times without response. Her electroencephalogram was diffusely slow with 2-3 Hz delta rhythm at the frontal regions. Audiological examination showed that she had sensorineural hearing loss in her left ear. Ophthalmologic evaluation revealed BRAO in both eyes. On the basis of these findings, she was diagnosed with SS and treated with intravenous immunoglobulin (IVIG) and aspirin. After monthly treatment with IVIG for 6 months, the patient has almost fully recovered. SS should be kept in mind in the differential diagnosis of MS and ADEM.

The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population.

OBJECTIVE: The aim was to investigate the frequency of genetic polymorphisms of cytochrome P4502C9 (CYP2C9) and vitamin K epoxide reductase complex subunit1 (VKORC1) and determine the effect of these polymorphisms on warfarin dose requirements in pediatric patients. METHODS: Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, aged 0.2-18 years, and with international normalized ratio (INR) between 2 and 3 and 149 healthy children as a control group were included in this prospective, observational study. Patients receiving drugs that interact with warfarin, having chronic liver or renal disease, obesity, or thyroid dysfunctions were excluded. Polymerase chain reaction (real time and restriction fragment length polymorphism) was used to analyze the CYP2C9*2, CYP2C9*3, and VKORC1 polymorphisms. The ideal warfarin dose was calculated according to the patient's age, height, and the presence of CYP2C9*2, CYP2C9*3, and VKORC1 genetic polymorphisms. The mean daily administered doses and ideal doses were compared. Analysis of variance, Student's t-test, logistic regression analysis, and Pearson's correlation analysis were used for statistical analyses. RESULTS: The frequency of the CYP2C9 and VKORC1 genetic polymorphisms was determined as CYP2C9*1/*1 (54.6%), *1/*2 (16.4%), *1/*3 (24.2%), *2/*3 (2.9%), *3/*3 (1.9%), wild-type VKORC1 (26.6%), heterozygote alleles (52.7%), and mutant alleles (20.8%). Patients with allelic variants were found to require lower warfarin doses, and a 64.5% correlation was found between the calculated ideal doses and the administered warfarin doses. CONCLUSION: Considering CYP2C9 and VKORC1 genetic polymorphisms prior to commencing warfarin treatment will make it easier to reach target INRs and reduce the rate of complications.

Predictors of recurrence in Sydenham's chorea: Clinical observation from a single center.

OBJECTIVE: Sydenham's chorea is the most common cause of acquired chorea in children and is the major manifestation for acute rheumatic fever. Despite being known as a benign, self-limiting condition, recurrences and persistence of symptoms can be seen. In this study, we aimed to evaluate retrospectively the clinical and laboratory features of patients with Sydenham's chorea and the rate and the course of recurrences, and to assess the risk of recurrences. METHODS: The study was a retrospective study conducted in a tertiary hospital. Patients with Sydenham's chorea who were admitted to our outpatient clinics between January 2013 and June 2015 were included. Both newly diagnosed and follow-up patients were enrolled during this period. We retrospectively reviewed the medical charts of the patients. RESULTS: There were 90 patients with female predominance. The mean age of onset was 11±2.4years. Complete remission was maintained in 77 patients (85.6%) at 1-6months and 4 patients had symptoms at more than 12months. Patients were followed for 6months to 9years. The recurrence rate was 16%. When we compared recurrent patients with the non-recurrent group, complete remission in 6months, the presence of persistent chorea, and regular use of prophylaxis were significantly different between the 2 groups. CONCLUSIONS: Sydenham's chorea is still an important health problem and has high morbidity in patients with recurrent and persistent chorea. The irregular usage of antibiotic prophylaxis, failure to achieve remission within 6months, and prolongation of symptoms for more than 1year are risk factors for recurrence of chorea.

Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation.

Childhood leukoencephalopathies are a broad class of diseases, which are extremely rare. The treatment and classification of these disorders are both challenging. Nearly half of children presenting with a leukoencephalopathy remain without a specific diagnosis. Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL) is a newly described childhood leukoencephalopathy caused by mutations in the gene encoding a mitochondrial aminoacyl-tRNA synthetase specific for glutamate, EARS2 Magnetic resonance images show a characteristic leukoencephalopathy with thalamic and brain stem involvement. Here, we report a different clinical course of LTBL supported by typical MRI features in a Turkish patient who presented with a history of failure to walk. The EARS2 gene mutation analysis identified a c.322C>T transition, predicting a p.R108W change. This is the first reported early-onset mild type LTBL caused by a homozygous EARS2 mutation case in the literature.