Evolution of antiseizure medication use and cost in the United States of America 2006-2021.

OBJECTIVE: To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA). METHODS: Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator. RESULTS: We evaluated 347,158 patients (46.9 % males; median (p25-p75) age: 33 (17-49) years; 28 % with pediatric-onset epilepsy and 72 % with adult-onset epilepsy) with a total of 1,385,382 person-years and 588,285,065 ASM prescription days. The most commonly prescribed (as percentage of prescription days) ASMs in 2006 were valproate (18 %) and lamotrigine (17 %) in pediatric-onset epilepsy and phenytoin (21 %) and carbamazepine (17 %) in adult-onset epilepsy, but starting in the 2010s, levetiracetam and lamotrigine became the most commonly prescribed ASMs in both pediatric-onset (in 2021, levetiracetam 25 %, lamotrigine 16 %) and adult-onset (in 2021, levetiracetam 27 %, lamotrigine 20 %) epilepsy. The proportion of generic ASM use increased 3.6-fold: from 23 % of prescription days in 2006 to 83 % of prescription days in 2021. The median (p25-p75) average wholesale price (AWP) per person-year increased by 102 % from $2,684 ($990-$5,509) in 2006 to $5,417 ($2,858-$12,310) in 2021. The increases were greater in absolute terms for brand-name ASMs by 419 %: $3,109 ($1,564-$5,068 in 2006 and $16,149 ($12,950-$23,377) in 2021 than for generic ASMs by 462 %: $699 ($457-$1,678) in 2006 and $3,931 ($2,618-$6,081) in 2021. The costs directly borne by the patient (copay, coinsurance, deductibles, and pharmacy processing fees) increased by 69 % for brand-name ASMs from $393 ($246-$570) in 2006 to $665 ($335-$1,308) in 2021, but decreased by 37 % for generic ASMs from $147 ($98-$213) in 2006 to $92 ($51-$141) in 2021. CONCLUSIONS: The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83 % of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.

Pediatric traumatic brain injuries in war zones: a systematic literature review.

Background: Pediatric casualties in war zones are a devastating consequence of armed conflicts, causing significant challenges for affected children, especially in the context of poor access to care. This study aimed to understand traumatic brain injuries (TBIs) in this high-risk population and to identify and provide information for the stakeholders, as well as to recognize severe long-term consequences and develop strategies to prevent them, thus minimizing their burden while aiding in the management of these cases. Methods: We carried out a systematic literature review following PRISMA guidelines to identify publications discussing traumatic brain injuries in children in the context of war zones, and we analyzed all the collected data. Results: Our study showed that head injuries were the most common casualty in war zones; male and female children were affected, and the mean age was 8-10 years. Most children were reported to be from Afghanistan, and blasts were the most common mechanism of injury. The mortality fluctuated from 3 to 47%. Conclusion: There is a lack of evidence-based information regarding the characterization, approach, and management of children with TBI in conflict zones. While the world finds ways to live in peace, there is an urgency to research, train, and deploy enough specialists to these areas, if governments are serious about improving outcomes for this population.

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

An Evaluation of Post-Concussion Return to School Guidelines: A Survey of Massachusetts School Nurses.

Although all states have legislation pertaining to youth sports concussion, most of these laws focus on return-to-play procedures; only a few address return-to-learn (RTL) accommodations for students who have experienced a concussion. To address this gap in the legislation, some states and nongovernmental organizations have developed RTL guidelines to advise school personnel, parents, and health care providers on best practices for accommodating students' postconcussion reintegration into academic activity. In 2018, the Massachusetts Department of Public Health (MDPH) developed RTL guidelines which were disseminated to school nurses (SNs) at all public and nonpublic middle and high schools in the state. In 2020, the MDPH engaged the Injury Prevention Center at Boston Medical Center to survey Massachusetts SNs to assess the usefulness of the guidelines. The response rate was 63%; 92% found the booklet extremely useful or moderately useful; and 70% endorsed that the booklet fostered collaboration among stakeholders.

Health care resource utilization and costs before and after epilepsy surgery.

OBJECTIVE: To describe the demographics of epilepsy surgery utilization and its impact on health care resource use. METHODS: Retrospective descriptive study using the MarketScan commercial claims database. We studied children and adults who underwent epilepsy surgery in the USA in the period 2006-2019. Our main outcome was health care resource utilization. RESULTS: Among the 87,368 patients with refractory epilepsy, 2,011 (2.3%) patients underwent resective epilepsy surgery, 188 (0.2%) patients underwent partial or total hemispherectomy, and 183 (0.2%) patients underwent corpus callosotomy. The proportion of patients undergoing epilepsy surgery has barely increased in the period 2006 to 2019. The year of resective epilepsy surgery was associated with high healthcare costs per person-year [median (p25-p75): $140,322 ($88,749-$225,862)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of resective epilepsy surgery [$7,691 ($2,738-$22,092) versus $18,750 ($7,361-$47,082), p-value < 0.0001]. This result held in all resective epilepsy surgery subgroups: children, adults, temporal, extratemporal, subdural EEG monitoring, stereoEEG monitoring, and no intracranial monitoring. Similarly, the year of hemispherectomy was associated with high healthcare costs per person-year [$260,983 ($154,791-$453,986)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of hemispherectomy [$26,834 ($12,842-$52,627) versus $54,596 ($19,547-$136,412), p-value < 0.0001]. In contrast, the year of corpus callosotomy was associated with high healthcare costs per person-year [$162,399 ($108,150-$253,156)], but healthcare costs per person-year did not substantially decrease in the 5 years after than in the 5 years before the year of corpus callosotomy [$25,464 ($10,764-$69,338) versus $36,221 ($12,841-$85,747), p-value = 0.2142]. CONCLUSION: In privately insured patients in the USA, resective epilepsy surgery and hemispherectomy substantially decrease healthcare utilization in subsequent years. Epilepsy surgery may help contain costs in the field of epilepsy.

[Autoimmune encephalitis in pediatric population]. / Encefalitis autoinmune en población pediátrica.

Autoimmune encephalitis can be defined as central nervous system inflammation, secondary to multiple causes, where we can possibly identify the formation of auto-antibody against neurotransmitter receptors or neuronal surface proteins. Approximately 50% of patients are seropositive; the auto-antibody against N-methyl-D-aspartate receptor (NMDAR) are the most common. In the pediatric population, the clinical presentation is characterized by movement disorders and seizures, psychiatric manifestations are more commonly found in young adults. An early intervention is associated with a better prognosis in these patients. In contrast to the seropositive group, seronegative autoimmune encephalitis is linked with less movement alterations and is related with a worse cognitive outcome. Much remains to be discovered about possible etiologies, molecular processes, detection, and interaction of yet undescribed antibodies,as well as increasing our knowledge about clinical manifestations in early disease and new diagnostic techniques that could improve the diagnosis of autoimmune encephalitis. The main goal of this document is to review the updates of the molecular field about the antibody against GluK2 and its clinical presentation in pediatric population; COVID-19 as a possible cause of autoimmune encephalitis; recognize the importance of psychiatric manifestation in early disease, especially catatonia as a marker of severity; additionally consider new imaging diagnostic method such as positron emission tomography (PET), which has shown to be more sensible than MRI (goal standard).

La encefalitis autoinmune se puede definir como el proceso inflamatorio del sistema nervioso central, secundario a múltiples causas donde se consigue identificar o no, la creación de auto-anticuerpos contra receptores de neurotransmisores o proteínas de la superficie neuronal. Aproximadamente un 50% de pacientes son seropositivos, el anticuerpo contra el receptor N-metil-D-aspartato (NMDAR) es encontrado con mayor frecuencia. La presentación clínica característica en la población pediátrica es la alteración del movimiento, seguido por episodios convulsivos; en edades más avanzadas, priman las manifestaciones psiquiátricas. Muestra buen pronóstico si se impone un pronto tratamiento. En la encefalitis autoinmune seronegativa, se observa una menor alteración de movimiento, la cual, contrario al grupo seropositivo, se asocia con peor pronóstico cognitivo. Falta mucho por conocer sobre las posibles etiologías, procesos moleculares, la interacción y detección de anticuerpos aún no descritos,al igual que es necesario incrementar nuestro conocimiento sobre las manifestaciones clínicas en etapa temprana de la enfermedad e investigar propuestas que podrían mejorar el diagnóstico de la encefalitis autoinmune. El objetivo de este documento es revisar las actualizaciones en el ámbito molecular sobre el nuevo anticuerpo descrito (GluK2) y su presentación clínica en la población pediátrica; COVID-19 como posible causa del desarrollo de encefalitis autoinmune; reconocer la importancia de las manifestaciones psiquiátricas en etapa temprana, en especial la catatonia como marcador de gravedad, de igual manera, considerar nuevas propuestas para el diagnóstico de encefalitis autoinmune como: tomografía por emisión de positrones (PET), que ha mostrado mayor sensibilidad al detectar anomalías cerebrales que la RMN (estudio de elección).

[Pediatric therapeutic options in autoimmune neurologic diseases]. / Opciones terapéuticas para enfermedades neurológicas autoinmunes en pediatría.

The pediatric neuroimmunology field has made significant progress in the last decade. Now, is possible to recognize primary demyelinating diseases, paraneoplastic syndromes, inflammatory (vasculitis), and granulomatous disorders that affect the central nervous system; at the same time, it is important to exclude neurologic manifestations caused by infections, toxic agents, and metabolic problems. An early diagnosis is imperative to institute treatment as soon as possible, improving outcomes. Treatment may include both, specific drugs if the etiology has been established, as well as drugs to treat potential complications, for example anticonvulsants, anti-inflammatory drugs, transfusions, or albumin replenishment within others. The main objective of this review is to provide guidance about the therapeutic options in pediatric autoimmune neurological diseases. We review the evidence and recommendations for the use of steroids in autoimmune demyelinating diseases, acute disseminated encephalomyelitis, optic neuritis, neuromyelitis optica, multiple sclerosis, among others. We will focus on current therapies, including high doses of intravenous methylprednisolone, followed by its progressive reduction, as well as intravenous immunoglobulin or plasmapheresis as second line therapies. Early institution of these treatments can save the patient's life and decrease their risk of permanent disability.

El campo de la pediatría neuro-inmunológica ha progresado significativamente en la última década. Ahora es posible reconocer con prontitud enfermedades desmielinizantes primarias, síndromes para-neoplásicos, enfermedades inflamatorias, autoinmunes y granulomatosas, que afectan el sistema nervioso central. Excluir con gran rapidez posibles causas infecciosas, agentes tóxicos, problemas metabólicos que se presenten con manifestaciones neurológicas es imperativo, ya que al hacer un diagnóstico preciso y temprano del paciente se puede instituir un tratamiento lo más pronto posible e incrementar las probabilidades de éxito. El tratamiento puede ser dirigido a la etiología específica, si se conoce. Adicionalmente, es importante tratar las complicaciones relacionadas a la propia enfermedad o efectos secundarios de los tratamientos que se impongan. El tratamiento puede incluir tanto fármacos específicos si se ha establecido la etiología, así como medicamentos para tratar posibles complicaciones, por ejemplo, anticonvulsivos, antiinflamatorios, transfusiones, o reposición de albúmina dentro de otros. El objetivo principal de esta revisión es brindar una guía sobre las opciones terapéuticas en enfermedades neurológicas autoinmunes en fase aguda. Revisamos la evidencia y recomendaciones acerca del uso de esteroides en enfermedades autoinmunes desmielinizantes, encefalomielitis aguda diseminada, neuritis óptica, neuromielitis óptica, esclerosis múltiple, entre otras, donde altas dosis de metilprednisolona, seguida por su disminución progresiva son esenciales, así como el uso de inmunoglobulina humana intravenosa y plasmaféresis, como tratamiento de segunda línea. La institución temprana de estos tratamientos puede salvar la vida del paciente y disminuir su discapacidad permanente.

Professional and Demographic Profile of Spanish-Speaking Child Neurologists in the United States.

>Objective: To ascertain the prevalence of culturally native Spanish-speaking child neurologists in the United States. Methods: Prevalence statistics regarding demographic and work profile were applied to data obtained from a cross-sectional electronic survey of Child Neurology Society (CNS) members. Results: Demographics of the 135 respondents were comparable to a similar CNS survey except for ethnicity as shown in Table 1. Fifty- three percent were male and 24% were over age 60. Approximately a quarter were represented each from East, South, Midwest, and Western US. 42% self-identified as Spanish, Hispanic, or Latino. 62% spoke English as their primary language and 39% spoke Spanish as their primary language. Two-thirds graduated from a US medical school, 51% practice general neurology, and epilepsy was the most common subspecialty (18%). Two-thirds of respondents practice at a major teaching hospital, and 93% hold university academic appointments. 79% are AAN members. 76% did not have medical student debt at the time of the survey. 29% report signs consistent with burnout. 87% would choose Child Neurology again and 96% would recommend Child Neurology to a medical student. Conclusion: 40% of survey respondents self-identified as Hispanic, Latino or Spanish and spoke Spanish as the primary language and the majority practice in Academic Medicine. Nearly a third of those in the current survey identify burnout symptoms. Consideration of distinctive language and cultural characteristics across the US may lead to provision of a more patient-centered and equitable care.

La atención en pacientes con lesión traumática cerebral / Care for patients with traumatic brain injury

Resumen La lesión traumática cerebral (LTC) al igual que el trastorno por déficit de atención con o sin hiperactividad (TDAH) son problemas muy frecuentes que afectan a los niños. Es conocido que los pacientes que sufren una lesión traumática cerebral pueden presentar síntomas del TDAH, los cuales a menudo pasan desapercibidos en el período agudo, especialmente cuando hay lesiones más graves que los ocultan y solo se evidencian cuando el paciente regresa a su actividad cognitiva regular después del alta. Los síntomas pueden variar dependiendo del mecanismo de lesión, el lugar del cerebro en donde ocurre el trauma o sus efectos, complicaciones y la severidad de la lesión. Algunos síntomas de LTC son idénticos a los del TDAH, haciendo que el diagnóstico de estos pacientes sea más difícil de discernir, ya sea porque el paciente o sus padres los reportan juntos cuando el paciente ya tenía un TDAH preexistente. Existen algunos escenarios clínicos que describimos en este artículo en los cuales hay una interacción entre estos dos, que se explican en parte porque ambos pueden afectar vías de conducción nerviosa y neurotransmisores similares. El clínico debe reconocer los problemas de atención en los pacientes con LTC y otras presentaciones y ofrecer tratamiento adecuado y opor tuno cuando los síntomas interfieren con el funcionamiento del paciente. El tratamiento del TDAH en pacientes con LTC usa acomodaciones y medicamentos similares a los que se usan en pacientes que solo tienen TDAH, pero dependiendo de la severidad pueden variar en su duración.

Abstract Traumatic brain injury (TBI) as well as Attention Deficit Disorder with or without hyperactivity (ADHD) are very common problems that affect children. It is known that patients who suffer a traumatic brain injury may present symptoms of ADHD, which often go un noticed in the acute period, especially when there are more serious injuries that hide them and are only evident when the patient returns to their regular cognitive activity after discharge. Symptoms can vary depending on the mechanism of injury, the location in the brain where the trauma or its effects occur, complications, and the severity of the injury. Some symptoms of TBI are identical to those of ADHD, making the diagnosis of these patients more difficult to discern either because the patient or their parents report them together or when the patient already had pre-existing ADHD. We describe some clinical scenarios in this article in which there is an interaction between these two processes that are explained in part because both can affect similar nerve conduction pathways and neurotransmitters. The clinician must recognize attention problems in patients with TBI and other presentations and offer appropriate and timely treatment when symptoms interfere with the patient's functioning. Treatment of ADHD in patients with TBI uses accommodations and medications similar to those used in patients who only have ADHD, but depending on the severity, they can vary in duration.

[Care for patients with traumatic brain injury]. / La atención en pacientes con lesión traumática cerebral.

Traumatic brain injury (TBI) as well as Attention Deficit Disorder with or without hyperactivity (ADHD) are very common problems that affect children. It is known that patients who suffer a traumatic brain injury may present symptoms of ADHD, which often go unnoticed in the acute period, especially when there are more serious injuries that hide them and are only evident when the patient returns to their regular cognitive activity after discharge. Symptoms can vary depending on the mechanism of injury, the location in the brain where the trauma or its effects occur, complications, and the severity of the injury. Some symptoms of TBI are identical to those of ADHD, making the diagnosis of these patients more difficult to discern either because the patient or their parents report them together or when the patient already had pre-existing ADHD. We describe some clinical scenarios in this article in which there is an interaction between these two processes that are explained in part because both can affect similar nerve conduction pathways and neurotransmitters. The clinician must recognize attention problems in patients with TBI and other presentations and offer appropriate and timely treatment when symptoms interfere with the patient's functioning. Treatment of ADHD in patients with TBI uses accommodations and medications similar to those used in patients who only have ADHD, but depending on the severity, they can vary in duration.

La lesión traumática cerebral (LTC) al igual que el trastorno por déficit de atención con o sin hiperactividad (TDAH) son problemas muy frecuentes que afectan a los niños. Es conocido que los pacientes que sufren una lesión traumática cerebral pueden presentar síntomas del TDAH, los cuales a menudo pasan desapercibidos en el período agudo, especialmente cuando hay lesiones más graves que los ocultan y solo se evidencian cuando el paciente regresa a su actividad cognitiva regular después del alta. Los síntomas pueden variar dependiendo del mecanismo de lesión, el lugar del cerebro en donde ocurre el trauma o sus efectos, complicaciones y la severidad de la lesión. Algunos síntomas de LTC son idénticos a los del TDAH, haciendo que el diagnóstico de estos pacientes sea más difícil de discernir, ya sea porque el paciente o sus padres los reportan juntos cuando el paciente ya tenía un TDAH preexistente. Existen algunos escenarios clínicos que describimos en este artículo en los cuales hay una interacción entre estos dos, que se explican en parte porque ambos pueden afectar vías de conducción nerviosa y neurotransmisores similares. El clínico debe reconocer los problemas de atención en los pacientes con LTC y otras presentaciones y ofrecer tratamiento adecuado y oportuno cuando los síntomas interfieren con el funcionamiento del paciente. El tratamiento del TDAH en pacientes con LTC usa acomodaciones y medicamentos similares a los que se usan en pacientes que solo tienen TDAH, pero dependiendo de la severidad pueden variar en su duración.

Spontaneous remission in juvenile myasthenia gravis: A cohort of 13 cases and review of the literature.

We describe the clinical course of patients with juvenile myasthenia gravis who experienced spontaneous remission and review the literature. This is a retrospective study of 13 patients with spontaneous remission from a cohort of 133 patients younger than 18-years-old. We compared several variables with potential prognostic value in patients with and without spontaneous remission. Ten percent of patients (13/133) experienced spontaneous remission. There was no difference in age at onset or sex compared to the overall JMG population. Spontaneous remission occurred in 2/40 (5.0%; 95% CI: 0.6-16.9) patients in Class I (ocular); in 11/53 (20.8%; 95% CI: 10.8-34.1) patients in Class II-III (mild, moderate, generalized) (p < 0.0018) and in 0/40 patients in Class IV-V (severe, needs intubation). Of the AChR antibody positive patients, 10/97 (10.3%; 95% CI: 5.0-18.1) had spontaneous remission, compared with 2/29 (6.9%; 95% CI: 0.9-22.8) of those without AChR antibodies (p = 0.583). Strikingly, none of the 36 patients with thyroid antibodies had spontaneous remission compared with 13/58 (22.4%) of those without thyroid antibodies (95% CI: 7.3-21.8; p < 0.001). Ten percent of patients with juvenile myasthenia gravis achieved spontaneous remission, mainly in those with Class II-III disease and no associated thyroid antibodies.

Paroxysmal hyperthermia, dysautonomia and rhabdomyolysis in a patient with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is an x-linked genetic disorder of purine metabolism that results in the overproduction of uric acid and neurologic deficits manifesting as intellectual disability, dystonia, other movement disorders and self-mutilation. We describe a 12-year-old patient with a history of Lesch-Nyhan syndrome, G6PD deficiency and central diabetes insipidus and multiple admissions for fever, acute kidney injury and transaminitis in the setting of rhabdomyolysis. The patient's temperature dysregulation and dysautonomia is likely attributable to abnormal neurotransmitter release, particularly that of dopamine, in the central nervous system. Our patient presented similarly to that of a patient with neuroleptic malignant syndrome (NMS), with symptoms including altered mental status, fever, dysautonomia and renal failure, and laboratory findings including elevated serum creatinine kinase, leukocytosis, transaminitis, hypernatremia and metabolic acidosis. Similar to NMS, disruption of dopamine neurotransmission results in dysregulated sympathetic activity and hyperthermia.

A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome.

Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking.Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures.Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.

Autoimmune Encephalitis in Children: From Suspicion to Diagnosis.

There are several well-described and studied autoimmune diseases that affect different organ systems, and a limited number of these affect the central nervous system. Autoimmune encephalitis represents a disease with a wide spectrum of clinical manifestations and different levels of severity, from mild cognitive impairment to complex encephalopathy. Immune-mediated encephalitis refers to a diverse and rare group of conditions in children associated with nonspecific symptomatology, altered mental state, and recalcitrant seizures. Infectious etiology must be excluded. Immune-mediated encephalitis syndromes could be associated with paraneoplastic or primarily autoimmune mechanisms. The newest scientific advantages have concluded that autoimmune encephalitis may be further divided into different groups of diseases depending on the immune response; examples are antibodies to cell surface proteins, antibodies to intracellular synaptic proteins, T-cell response with antibodies to intracellular antigens, among others. Treatment consists of supportive therapy, ranging from supplemental oxygen, fluid restriction to mechanical circulatory support. Specific treatment includes immunoglobulin infusion, plasmapheresis, and pulse steroid treatment. Prognosis is poor if specific treatment is not timely instituted. The diagnosis of autoimmune encephalitis could be challenging to clinicians due to its diverse clinical features, which can mimic a variety of other pathologic processes. Screening for cancer and proper management that includes immune therapy are fundamental, although some patients will need immune suppression for weeks or months as autoimmune encephalitis may relapse; therefore, follow-up is always necessary.

Assessment and Treatment of Concussion in the Pediatric Population.

Traumatic brain injury (TBI) is common in children. The evaluation and management of children with TBI is based on the research performed in adults. There is a relative paucity of research in the literature involving children and many of the practice recommendations for this age are based on expert opinion in the absence of good research studies in both sports and non-sports-related injuries. The pediatric population is heterogeneous and the approach might be specific for infants, preschoolers, school age children, and adolescents. Children may also suffer from neurodevelopmental disabilities, making their evaluation even more challenging. Adult neurologists are often asked to see children due to increasing demands. This review will focus on specific issues related to TBI in children that might be useful to adult neurologists. Science, however, is evolving rapidly and physicians should make sure to remain up to date to offer evidence-based services to their patients.

It is time to rewrite state youth sports concussion laws.

Between 2009 and 2014, all 50 states and the District of Columbia passed legislation to improve the recognition and management of youth concussed in sports. These laws can include requirements for concussion training for school athletic personnel, concussion education for children and their parents, return-to-play (RTP) procedures, and medical clearance to for RTP. Concussion can impact academic learning and performance in children and adolescents. Postconcussion academic accommodations during recovery can be an important component of secondary prevention for mitigating the sequalae of head injury. Few state youth concussion laws, however, include provision of postconcussion return-to-learn (RTL) accommodations and most of those that do address RTL apply to student athletes only. Concussions may occur in youth who are not participating in organised sports (eg, falls, traffic crashes) and thus may not be subjected to RTL accommodations, even if the state mandates such procedures for athletes. Low income and students of colour may be more likely to have non-sports concussions than their more affluent and white peers, thus potentially creating demographic disparities in the benefits of RTL procedures. State youth sports concussion laws should be revised so that they include RTL provisions that apply to all students, athletes and non-athletes alike.