Transcutaneous Spinal Cord Stimulation Enables Recovery of Walking in Children with Acute Flaccid Myelitis.

Background: Limited research exists for use of transcutaneous spinal stimulation (TSS) in pediatric spinal cord injuries (SCI) to improve walking outcomes, especially in children diagnosed with SCI secondary to acute flaccid myelitis (AFM).

Objective: This case series demonstrates the feasibility and efficacy of TSS paired with gait training in children diagnosed with AFM.

Methods: A total of 4 participants diagnosed with incomplete SCI secondary to AFM completed 22, 2-h therapy sessions over 5-8 weeks.

Transcutaneous Spinal Stimulation From Adults to Children: A Review.

Neuromodulation via spinal stimulation is a promising therapy that can augment the neuromuscular capacity for voluntary movements, standing, stepping, and posture in individuals with spinal cord injury (SCI). The spinal locomotor-related neuronal network known as a central pattern generator (CPG) can generate a stepping-like motor output in the absence of movement-related afferent signals from the limbs. Using epidural stimulation (EP) in conjunction with activity-based locomotor training (ABLT), the neural circuits can be neuromodulated to facilitate the recovery of locomotor functions in persons with SCI.

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk.

Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the 'Developmental Origins of Health and Disease' (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction.

Monoallelic IDH1 R132H Mutation Mediates Glioma Cell Response to Anticancer Therapies via Induction of Senescence.

Heterozygous isocitrate dehydrogenase (IDH) R132H mutation (IDH1) is an early event during gliomagenesis. Clinically, patients with glioma carrying mutant IDH1 respond better to antitumor therapies. However, the mechanism by which IDH1 mutations contribute to gliomagenesis and therapeutic response remains elusive.

Feasibility and utility of transcutaneous spinal cord stimulation combined with walking-based therapy for people with motor incomplete spinal cord injury.

Study Design: Prospective case series.

Objectives: To evaluate the feasibility and preliminary efficacy of combining transcutaneous spinal cord stimulation (TSCS) with walking-based physical therapy.

Setting: Hospital-based outpatient center in Maryland, United States.

Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

Background: Pathogenic variants in the FKRP gene cause impaired glycosylation of α-dystroglycan in muscle, producing a limb-girdle muscular dystrophy with cardiomyopathy. Despite advances in understanding the pathophysiology of FKRP-associated myopathies, clinical research in the limb-girdle muscular dystrophies has been limited by the lack of normative biomarker data to gauge disease progression.

Methods: Participants in a phase 2 clinical trial were evaluated over a 4-month, untreated lead-in period to evaluate repeatability and to obtain normative data for timed function tests, strength tests, pulmonary function, and body composition using DEXA and whole-body MRI.

Duchenne muscular dystrophy hiPSC-derived myoblast drug screen identifies compounds that ameliorate disease in mdx mice.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. In the present study, when human induced pluripotent stem cells (hiPSCs) were differentiated into myoblasts, the myoblasts derived from DMD patient hiPSCs (DMD hiPSC-derived myoblasts) exhibited an identifiable DMD-relevant phenotype: myogenic fusion deficiency. Based on this model, we developed a DMD hiPSC-derived myoblast screening platform employing a high-content imaging (BD Pathway 855) approach to generate parameters describing morphological as well as myogenic marker protein expression.

Diabetes, metformin and cancer risk in myotonic dystrophy type I.

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population.

Stem cell-based therapies for Duchenne muscular dystrophy.

Muscular dystrophies are a group of genetic muscle disorders that cause progressive muscle weakness and degeneration. Within this group, Duchenne muscular dystrophy (DMD) is the most common and one of the most severe. DMD is an X chromosome linked disease that occurs to 1 in 3500 to 1 in 5000 boys.

Benign tumors in myotonic dystrophy type I target disease-related cancer sites.

Objectives: Recent evidence showed that myotonic dystrophy type I (DM1) patients are at increased risk of certain cancers, but the risk of benign tumors is unknown. We compared the risk of benign tumors in DM1 patients with matched DM1-free individuals and assessed the association between benign tumors and subsequent cancers.

Methods: We identified 927 DM1 patients and 13,085 DM1-free individuals matched on gender, birth-year, clinic, and clinic-registration year from the UK Clinical Practice Research Datalink, a primary care records database.

Expansion of the clinical spectrum associated with AARS2-related disorders.

Biallelic pathogenic variants in AARS2, a gene encoding the mitochondrial alanyl-tRNA synthetase, result in a spectrum of findings ranging from infantile cardiomyopathy to adult-onset progressive leukoencephalopathy. In this article, we present three unrelated individuals with novel compound heterozygous pathogenic AARS2 variants underlying diverse clinical presentations. Patient 1 is a 51-year-old man with adult-onset progressive cognitive, psychiatric, and motor decline and leukodystrophy.

Advancements in magnetic resonance imaging-based biomarkers for muscular dystrophy.

Recent years have seen steady progress in the identification of genetic muscle diseases as well as efforts to develop treatment for these diseases. Consequently, sensitive and objective new methods are required to identify and monitor muscle pathology. Magnetic resonance imaging offers multiple potential biomarkers of disease severity in the muscular dystrophies.

Interdisciplinary, Intensive, Activity-Based Treatment for Intrauterine Spinal Cord Infarct: A Case Report.

Intrauterine spinal cord infarcts (IUSCI) with resulting tetraplegia are extremely rare, and there is minimal evidence describing outcomes in this population. This case describes the functional progress of a 3-year-old girl born with IUSCI who participated in activity-based therapies (ABT). Children have developing nervous systems and are particularly suited to benefit from ABT.

Cancer Risk in Myotonic Dystrophy Type I: Evidence of a Role for Disease Severity.

Background: Myotonic dystrophy type 1 (DM1) is an inherited trinucleotide repeat disorder in which specific cancers have been implicated as part of the disease phenotype. This study aimed to assess whether cancer risk in DM1 patients is modified by disease severity.

Methods: Using the United Kingdom Clinical Practice Research Datalink (primary care electronic medical records), we identified a cohort of 927 DM1 and a matched cohort of 13 085 DM1-free individuals between January 1, 1988 and February 29, 2016.

Clinical whole-exome sequencing results impact medical management.

Background: Clinical diagnostic whole-exome sequencing (WES) is a powerful tool for patients with undiagnosed genetic disorders. To demonstrate the clinical utility, we surveyed healthcare providers (HCP) about changes in medical management and treatment, diagnostic testing, reproductive planning, and use of educational services subsequent to WES testing.

Methods: For a period of 18 months, an 18-question survey was sent to HCPs attached to the WES reports.

Monogenic disorders that mimic the phenotype of Rett syndrome.

Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2 (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can lead to presentations that resemble, but do not completely mirror, classical RTT.

Multivoxel proton magnetic resonance spectroscopy in facioscapulohumeral muscular dystrophy.

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. This study evaluates the use of proton magnetic resonance spectroscopy ( H MRS) as a biomarker of muscle strength and function in FSHD.

Methods: Thirty-six individuals with FSHD and 15 healthy controls underwent multivoxel H MRS of a cross-section of the mid-thigh.

Characteristics of individuals seeking activity-based restorative therapy following spinal cord injury: A focus on hope.

Background: There is a lack of evidence regarding the psychosocial characteristics of individuals with spinal cord injury (SCI) undergoing activity-based restorative therapy (ABRT) treatment.

Objectives: This study seeks to describe the hopefulness of a sample of ABRT participants and describe the relationship between hopefulness and level of rehabilitation engagement.

Methods: A prospective cross-sectional cohort study was conducted using a convenience sample of 73 individuals with SCI (mean time since injury = 66.

Epileptic Encephalopathy Due to Pathogenic Variants.

Investigators from Institut für Medizinische Genetik und Humangenetik have highlighted the role of compound heterozygous variants in two German brothers with variable presentations of intractable epilepsy, poor development, postnatal microcephaly, hypertonia, apnea, and infantile/childhood death.

The musical centers of the brain: Vladimir E. Larionov (1857-1929) and the functional neuroanatomy of auditory perception.

In 1899 a landmark paper entitled "On the musical centers of the brain" was published in Pflügers Archiv, based on work carried out in the Anatomo-Physiological Laboratory of the Neuropsychiatric Clinic of Vladimir M. Bekhterev (1857-1927) in St. Petersburg, Imperial Russia.

BRAT1 mutations present with a spectrum of clinical severity.

Mutations in BRAT1, encoding BRCA1-associated ATM activator 1, are associated with a severe phenotype known as rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL; OMIM # 614498), characterized by intractable seizures, hypertonia, autonomic instability, and early death. We expand the phenotypic spectrum of BRAT1 related disorders by reporting on four individuals with various BRAT1 mutations resulting in clinical severity that is either mild or moderate compared to the severe phenotype seen in RMFSL. Representing mild severity are three individuals (Patients 1-3), who are girls (including two sisters, Patients 1-2) between 4 and 10 years old, with subtle dysmorphisms, intellectual disability, ataxia or dyspraxia, and cerebellar atrophy on brain MRI; additionally, Patient 3 has well-controlled epilepsy and microcephaly.

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery.

Dystrophin-deficient dogs with reduced myostatin have unequal muscle growth and greater joint contractures.

Background: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition.

Traumatic Spinal Cord Injury Emergency Service Triage Patterns and the Associated Emergency Department Outcomes.

Paralysis is an indication for trauma patients to be preferentially triaged by emergency services to designated level I or II trauma centers (TC). We sought to describe triage practices for patients with acute traumatic spinal cord injury (TSCI) and its associated emergency department (ED) outcomes. Adults ages ≥ 18 years with a diagnosis of acute TSCI (International Classification of Diseases-9: 806 and 952) in the 2006-2011 United States Nationwide Emergency Department Sample were included in these analyses.

Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings.

Recently, mutations in FARS2, which encodes for mitochondrial phenylalanyl-tRNA synthetase, have been implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. Associated clinical features in three previously reported patients with confirmed FARS2 mutations include infantile onset epilepsy, and a fatal Alpers-like encephalopathy. Herein, we report on two siblings with global developmental delay, dysarthria and tremor and compound heterozygous FARS2 abnormalities.