Search

Objective: This article provides a comprehensive overview of the diagnostic assessment and treatment of individuals with spinal muscular atrophy (SMA) due to homozygous deletions of SMN1 ., Latest Developments: In recent years, most states have incorporated SMA in their newborn screening panel. To provide the earliest diagnosis possible after symptom onset, vigilance is needed for births in states without newborn screening for SMA and when compound heterozygotes are missed by newborn screening programs. Supportive care for respiratory, nutritional, and orthopedic health impacts outcomes and is the cornerstone of care. Adaptive equipment, including assistive home technology, enables affected individuals to gain autonomy in their daily activities. Pharmacologic treatments approved by the US Food and Drug Administration (FDA) include three drugs that increase deficient survival motor neuron protein levels through SMN1 - or SMN2 - directed pathways: nusinersen, onasemnogene abeparvovec, and risdiplam. Efficacy for these trials was measured in event-free survival (survival without the need for permanent ventilation) and gains in functional motor outcomes. Earlier treatment is most effective across all treatments., Essential Points: The diagnostic and therapeutic landscapes for SMA have seen dramatic advancements in recent years, improving prognosis. Optimized supportive care remains essential, and vigilance is needed to define the new natural history of this disease., (Copyright © 2023 American Academy of Neurology.)

Background: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion or loss-of-function mutations of the survival of motor neuron 1 (SMN1) gene, resulting in reduced levels of SMN protein throughout the body. Patients with SMA may have multiple tissue defects, which could present prior to neuromuscular symptoms., Objective: To assess the signs, comorbidities and potential extraneural manifestations associated with SMA in treatment-naïve patients., Methods: This observational, retrospective and matched-cohort study used secondary insurance claims data from the US IBM® MarketScan® Commercial, Medicaid and Medicare Supplemental databases between 01/01/2000 and 12/31/2013. Treatment-naïve individuals aged≤65 years with≥2 International Classification of Diseases, Ninth Revision (ICD-9) SMA codes were stratified into four groups (A-D), according to age at index (date of first SMA code recorded) and type of ICD-9 code used, and matched with non-SMA controls. The occurrence of ICD-9 codes, which were converted to various classifications (phecodes and system classes), were compared between groups in pre- and post-index periods., Results: A total of 1,457 individuals with SMA were included and matched to 13,362 controls. Increasing numbers of SMA-associated phecodes and system classes were generally observed from pre- to post-index across all groups. The strongest associations were observed in the post-index period for the youngest age groups. Endocrine/metabolic disorders were associated with SMA in almost all groups and across time periods., Conclusions: This exploratory study confirmed the considerable disease burden in patients with SMA and identified 305 unique phecodes associated with SMA, providing a rationale for further research into the natural history and progression of SMA, including extraneural manifestations of the disease.

Objective: To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine., Methods: We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence., Results: There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache-free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia., Recommendations: Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counseling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse., (© 2019 American Academy of Neurology.)

Objective: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population., Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended., Results: Fifteen Class I-III studies on migraine prevention in children and adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, or flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency., Recommendations: The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision-making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments., (© 2019 American Academy of Neurology.)

Objective: To update the 2005 American Academy of Neurology (AAN) guideline on corticosteroid treatment of Duchenne muscular dystrophy (DMD)., Methods: We systematically reviewed the literature from January 2004 to July 2014 using the AAN classification scheme for therapeutic articles and predicated recommendations on the strength of the evidence., Results: Thirty-four studies met inclusion criteria., Recommendations: In children with DMD, prednisone should be offered for improving strength (Level B) and pulmonary function (Level B). Prednisone may be offered for improving timed motor function (Level C), reducing the need for scoliosis surgery (Level C), and delaying cardiomyopathy onset by 18 years of age (Level C). Deflazacort may be offered for improving strength and timed motor function and delaying age at loss of ambulation by 1.4-2.5 years (Level C). Deflazacort may be offered for improving pulmonary function, reducing the need for scoliosis surgery, delaying cardiomyopathy onset, and increasing survival at 5-15 years of follow-up (Level C for each). Deflazacort and prednisone may be equivalent in improving motor function (Level C). Prednisone may be associated with greater weight gain in the first years of treatment than deflazacort (Level C). Deflazacort may be associated with a greater risk of cataracts than prednisone (Level C). The preferred dosing regimen of prednisone is 0.75 mg/kg/d (Level B). Over 12 months, prednisone 10 mg/kg/weekend is equally effective (Level B), with no long-term data available. Prednisone 0.75 mg/kg/d is associated with significant risk of weight gain, hirsutism, and cushingoid appearance (Level B)., (© 2016 American Academy of Neurology.)

Aim: The association between socio-economic status (SES) and cerebral palsy (CP) remains controversial. Preterm birth, low birthweight, and postnatal injuries are accepted mediating risk factors for CP, but the question remains whether SES confers additional risk. The aim of this study was to analyse existing knowledge on the relationship between SES and the risk of CP., Method: We conducted a systematic search and review of potentially relevant research relating to SES and CP published from 1980 to 2012. Heterogeneity between studies did not allow for data aggregation or meta-analysis; therefore, a narrative review was used to summarize the findings., Results: Twelve studies were included in the systematic review. Of these, eight found low SES to be a risk factor for increased CP prevalence. Three studies detected statistically significant associations even after controlling for birthweight and gestational age as variables. Two of these studies also accounted for additional confounding variables (multiple births and timing of CP acquisition) and continued to detect contributory effects of SES. Linear negative correlations between CP prevalence and SES were shown by three studies., Interpretation: Evidence suggests that the effect of SES on CP prevalence goes beyond that of the mediating factors preterm birth, low birthweight, and postnatal trauma. These associations were seen in area-based and, to a lesser extent, individual measures of SES. A better understanding of mediating factors is imperative in developing targeted public health intervention programmes to reduce the prevalence of CP., (© 2014 Mac Keith Press.)