Eye movement defects in KO zebrafish reveals SRPK3 as a causative gene for an X-linked intellectual disability.

Intellectual disability (ID) is a common neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. X-linked ID (XLID) disorders, caused by defects in genes on the X chromosome, affect 1.7 out of 1,000 males. Employing exome sequencing, we identified three missense mutations (c.475C>G; p.H159D, c.1373C>A; p.T458N, and c.1585G>A; p.E529K) in the SRPK3 gene in seven XLID patients from three independent families. Clinical features common to the patients are intellectual disability, agenesis of the corpus callosum, abnormal smooth pursuit eye movement, and ataxia. SRPK proteins are known to be involved in mRNA processing and, recently, synaptic vesicle and neurotransmitter release. In order to validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. In day 5 of larval stage, KO zebrafish showed significant defects in spontaneous eye movement and swim bladder inflation. In adult KO zebrafish, we found agenesis of cerebellar structures and impairments in social interaction. These results suggest an important role of SRPK3 in eye movements, which might reflect learning problems, intellectual disability, and other psychiatric disorders.

Electrodiagnosis of Common Mononeuropathies: Median, Ulnar, and Fibular (Peroneal) Neuropathies.

This article addresses common mononeuropathies seen in the electrodiagnostic laboratory. The most common mononeuropathies-median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, and fibular (peroneal) neuropathy at the fibular head-are reviewed. The causes, clinical presentations, approached to the electrodiagnostic studies (including nerve conduction studies and needle electromyography), and the typical findings are discussed.

Diabetic neuropathies.

Diabetic neuropathies are the most common type of neuropathies seen in clinical practice. These neuropathies can range clinically from asymptomatic to manifesting symptoms caused by motor, sensory, and autonomic nerve dysfunction. These neuropathies can affect the peripheral nervous system, pain receptors, cardiovascular, urogenital, and gastrointestinal systems. This monograph presents an overview of the different types of diabetic neuropathies, their presentations, diagnostic tools, and strategies for management.

Entrustable professional activities: A useful concept for neurology education.

Medical education is currently undergoing a paradigm shift from process-based to competency-based education, focused on measuring the desired competence of a physician. In an attempt to improve the assessment framework used for medical education, the concept of entrustable professional activities (EPAs) has gained traction. EPAs are defined as professional activities that can be entrusted to an individual in a clinical context. The Association of American Medical Colleges (AAMC) defined a set of 13 such EPAs to define the core of what all students should be able to do on day 1 of residency, regardless of specialty choice. The AAMC is currently piloting these EPAs with 10 medical schools to determine if EPAs can be used as a way to observe, measure, and entrust medical students with core clinical activities by the end of the clinical immersion experiences of the third year. The specialty of pediatrics is piloting the use of specialty-specific EPAs at 5 medical schools to assess readiness for transitions from medical school into pediatric residency training and practice. To date, no neurology-specific EPAs have been published for use in neurology clerkships or neurology residencies. This article introduces the concept of EPAs in the context of competency-based medical education and describes how EPAs might be relevant and applicable in neurologic education across the continuum. The Undergraduate Education Subcommittee of the American Academy of Neurology advocates for a proactive approach to incorporating core EPAs in undergraduate medical education and to considering an EPA-based specialty-specific assessment framework for neurology.

ALS and other motor neuron diseases.

PURPOSE OF REVIEW: This review describes the most common motor neuron disease, ALS. It discusses the diagnosis and evaluation of ALS and the current understanding of its pathophysiology, including new genetic underpinnings of the disease. This article also covers other motor neuron diseases, reviews how to distinguish them from ALS, and discusses their pathophysiology. RECENT FINDINGS: In this article, the spectrum of cognitive involvement in ALS, new concepts about protein synthesis pathology in the etiology of ALS, and new genetic associations will be covered. This concept has changed over the past 3 to 4 years with the discovery of new genes and genetic processes that may trigger the disease. As of 2014, two-thirds of familial ALS and 10% of sporadic ALS can be explained by genetics. TAR DNA binding protein 43 kDa (TDP-43), for instance, has been shown to cause frontotemporal dementia as well as some cases of familial ALS, and is associated with frontotemporal dysfunction in ALS. SUMMARY: The anterior horn cells control all voluntary movement: motor activity, respiratory, speech, and swallowing functions are dependent upon signals from the anterior horn cells. Diseases that damage the anterior horn cells, therefore, have a profound impact. Symptoms of anterior horn cell loss (weakness, falling, choking) lead patients to seek medical attention. Neurologists are the most likely practitioners to recognize and diagnose damage or loss of anterior horn cells. ALS, the prototypical motor neuron disease, demonstrates the impact of this class of disorders. ALS and other motor neuron diseases can represent diagnostic challenges. Neurologists are often called upon to serve as a "medical home" for these patients: coordinating care, arranging for durable medical equipment, and leading discussions about end-of-life care with patients and caregivers. It is important for neurologists to be able to identify motor neuron diseases and to evaluate and treat patients affected by them.

A competency-based longitudinal core curriculum in medical neuroscience.

Current medical educational theory encourages the development of competency-based curricula. The Accreditation Council for Graduate Medical Education's 6 core competencies for resident education (medical knowledge, patient care, professionalism, interpersonal and communication skills, practice-based learning, and systems-based practice) have been embraced by medical schools as the building blocks necessary for becoming a competent licensed physician. Many medical schools are therefore changing their educational approach to an integrated model in which students demonstrate incremental acquisition and mastery of all competencies as they progress through medical school. Challenges to medical schools include integration of preclinical and clinical studies as well as development of learning objectives and assessment measures for each competency. The Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN) assembled a group of neuroscience educators to outline a longitudinal competency-based curriculum in medical neuroscience encompassing both preclinical and clinical coursework. In development of this curriculum, the committee reviewed United States Medical Licensing Examination content outlines, Liaison Committee on Medical Education requirements, prior AAN-mandated core curricula for basic neuroscience and clinical neurology, and survey responses from educators in US medical schools. The newly recommended curriculum provides an outline of learning objectives for each of the 6 competencies, listing each learning objective in active terms. Documentation of experiences is emphasized, and assessment measures are suggested to demonstrate adequate achievement in each competency. These guidelines, widely vetted and approved by the UES membership, aspire to be both useful as a stand-alone curriculum and also provide a framework for neuroscience educators who wish to develop a more detailed focus in certain areas of study.