Thrombotic Microangiopathy Associated with Systemic Adeno-Associated Virus Gene Transfer: Review of Reported Cases.

Complement-mediated thrombotic microangiopathy (TMA) in the form of atypical hemolytic uremic syndrome (aHUS) has emerged as an immune complication of systemic adeno-associated virus (AAV) gene transfer that was unforeseen based on nonclinical studies. Understanding this phenomenon in the clinical setting has been limited by incomplete data and a lack of uniform diagnostic and reporting criteria. While apparently rare based on available information, AAV-associated TMA/aHUS can pose a substantial risk to patients including one published fatality.

Validation of an ambient measurement system (AMS) for physical activities in a paediatric population.

Ambient measurement systems (AMSs) can enable continuous assessment of functional performance at home, increasing the availability of data for monitoring of neuromuscular disease. An AMS passively measures movement whenever someone is in range of the sensor, without the need for any wearable sensors. The current study evaluates the performance of an AMS for three metrics associated with functional assessments in Duchenne muscular dystrophy (DMD): ambulation speed, rise-to-stand speed and arm-raise speed.

Disease-related determinants of quality of life 10 years after clinically isolated syndrome.

Background: The main clinical determinants of quality of life (QOL) 5 years after clinically isolated syndrome (CIS) are Expanded Disability Status Scale (EDSS) score and conversion to clinically definite multiple sclerosis (CDMS). The aim of this study was to determine the demographic, clinical, and magnetic resonance imaging (MRI) factors associated with QOL 10 years after CIS.

Methods: Controlled High Risk Avonex® Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS) 10-year patients were assessed for CDMS, EDSS score, MRI T2 activity, brain parenchymal fraction, and patient-reported QOL.

Treatment discontinuation and disease progression with injectable disease-modifying therapies: findings from the north american research committee on multiple sclerosis database.

Injectable first-line disease-modifying therapies (DMTs) for multiple sclerosis (MS) are generally prescribed for continuous use. Accordingly, the various factors that influence patient persistence with treatment and that can lead some patients to switch medications or discontinue treatment may affect clinical outcomes. Using data from the North American Research Committee on Multiple Sclerosis (NARCOMS) database, this study evaluated participants' reasons for discontinuation of injectable DMTs as well as the relationship between staying on therapy and sustained patient-reported disease progression and annualized relapse rates.

Aggressive relapsing multiple sclerosis characterized by rapid disability progression.

Background: Criteria for identifying relapsing multiple sclerosis (RMS) patients with aggressive disease, which would be useful for clinical decision making, are currently unavailable.

Objective: Identify RMS patients with aggressive disease characterized by rapid disability progression.

Methods: Data from a 2-year, phase 3, double-blind, placebo-controlled trial with long-term follow-up evaluations of RMS patients taking either intramuscular interferon beta-1a (IM IFNβ-1a, 30μg) or placebo with baseline Expanded Disability Status Scale (EDSS) scores of 1.

Derivation of a new ADAS-cog composite using tree-based multivariate analysis: prediction of conversion from mild cognitive impairment to Alzheimer disease.

Model-based statistical approaches were used to compare the ability of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), cerebrospinal fluid (CSF), fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance imaging (MRI) markers to predict 12-month progression from mild cognitive impairment (MCI) to Alzheimer disease (AD). Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set, properties of the 11-item ADAS-cog (ADAS.11), the 13-item ADAS-cog (ADAS.

Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study.

Objective: The objective of this long-term open-label study in adolescents was to assess the safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches.

Background: Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long-term safety data on agents for migraine prevention are lacking for this younger population.

Safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches: results of an open-label extension trial in adolescents.

Objective: To evaluate the long-term safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches in adolescents.

Background: Divalproex sodium has been approved for migraine prophylaxis in adults. A previous double-blind, placebo-controlled study of the efficacy and safety of divalproex sodium extended-release for prevention of migraine in adolescents was followed by the present long-term extension trial, which was designed to collect additional safety and tolerability data.

Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study.

Objective: To evaluate the efficacy, tolerability, and safety of 3 different doses of divalproex sodium extended-release vs placebo in the prophylaxis of migraine headaches in adolescents.

Background: Divalproex sodium has been approved for migraine prophylaxis in adults, and previous uncontrolled data suggest divalproex sodium may be effective in preventing migraine in children and adolescents with acceptable tolerability.

Methods: This was a 12-week, phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter study in approximately 300 adolescents aged 12 to 17 years with migraine headaches.

The molecular pathology of Rett syndrome: synopsis and update.

Genetic mutations of the X-linked gene MECP2, encoding methyl-CpG-binding protein 2, cause Rett syndrome (RTT) and other neurological disorders. It is increasingly recognized that MECP2 is a multifunctional protein, with at least four different functional domains: (1) a methyl-CpG-binding domain; (2) an arginine-glycine repeat RNA-binding domain; (3) a transcriptional repression domain; and (4) an RNA splicing factor binding region (WW group II binding domain). There is evidence that MECP2 is important for large-scale reorganization of pericentromeric heterochromatin during differentiation.