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Brain Nerve 2021 Jun;73(6):659-670

Department of Neurology, Chubu Rosai Hospital.

The most caudal part of the spinal cord shows special anatomical characteristics and it contains epiconus (L4-S2 segments), the conus medullaris (S3-S5 segments), and surrounding nerve roots. Lesions of the thoracolumbar junction cause epiconus or conus syndrome. Epiconus syndrome is characterized by segmental muscular weakness and atrophy of one or both lower extremities, often accompanied by foot drop. Read More

J Anat 2021 Jun 13. Epub 2021 Jun 13.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.

Analysis of rodent muscles affords an opportunity to glean key insights into neuromuscular development and the detrimental impact of disease-causing genetic mutations. Muscles of the distal leg, for instance the gastrocnemius and tibialis anterior, are commonly used in such studies with mice and rats. However, thin and flat muscles, which can be dissected, processed and imaged without major disruption to muscle fibres and nerve-muscle contacts, are more suitable for accurate and detailed analyses of the peripheral motor nervous system. Read More

Orphanet J Rare Dis 2021 Jun 13;16(1):274. Epub 2021 Jun 13.

Cardiology Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Shuaifuyuan 1#, Beijing, 100730, China.

Background: This observational study describes our experience delivering nusinersen through lumbar puncture with real-time ultrasound guidance in spinal muscular atrophy (SMA) patients with severe scoliosis.

Results: Intrathecal nusinersen via real-time ultrasound-guided lumbar puncture was given to three patients who had severe thoracic and lumbar scoliosis: a 34-year-old female with type 3a SMA, a 28-year-old male with type 2a SMA, and a 14-year-old girl with type 3a SMA. Lumbar puncture was performed without sedation under ultrasound guidance using a 22G echogenic needle in the interlaminar aspect of the L4-L5 or L5-S1 interspace and a full dose of nusinersen (12 mg/5 mL) was injected after visualizing free cerebrospinal fluid flow. Read More

Value Health 2021 Jun 10;24(6):839-845. Epub 2021 May 10.

The Institute for Clinical and Economic Review, Boston, MA, USA. Electronic address:

Objectives: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies.

Methods: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. Read More

Value Health 2021 Jun 31;24(6):759-769. Epub 2021 Mar 31.

The National Health Care Institute, Diemen, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Objectives: Onasemnogene Abeparvovec-xioi (AVXS-101) is a gene therapy intended for curative treatment of spinal muscular atrophy (SMA) with an expected price of around €2 000 000. The goal of this study is to perform a cost-effectiveness analysis of treatment of SMA I patients with AVXS-101 in The Netherlands including relapse scenarios.

Methods: An individual-based state-transition model was used to model treatment effect and survival of SMA I patients treated with AVXS-101, nusinersen and best supportive care (BSC). Read More

BMC Musculoskelet Disord 2021 Jun 12;22(1):536. Epub 2021 Jun 12.

Orthopedics, Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, China.

Background: Degenerative lumbar spinal stenosis (DLSS) is a common degenerative condition in older adults. Muscle atrophy (MA) is a leading cause of muscle weakness and disability commonly reported in individuals with spinal stenosis. The purpose of this study was to investigate if the MA correlates with the grade of spinal stenosis in patients with DLSS. Read More

J Cachexia Sarcopenia Muscle 2021 Jun 11. Epub 2021 Jun 11.

Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD, USA.

Background: Spinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. Read More

Rev Med Chil 2021 Jan;149(1):142-146

Servicio de Neurología, Hospital del Salvador, Santiago, Chile.

Monomelic amyotrophy, also known as Hirayama disease, is a rare lower motor neuron syndrome due to localized lower motor neuron loss in the spinal cord at the cervical level. Clinically, monomelic amyotrophy is defined by the insidious onset of unilateral atrophy and weakness involving the hand and forearm, typically beginning in the second or third decade of life. We report 19-year-old man with a two years history of slowly progressive unilateral weakness and atrophy of his right-hand muscles. Read More

Neuromuscul Disord 2021 Apr 2. Epub 2021 Apr 2.

Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address:

Previous natural history studies suggest that type II SMA patients remain stable over one year but show some progression over two years. Since nusinersen approval, there has been increasing attention to identify more specific age-related changes. The aim of the study was to establish 12-month changes in a cohort of pediatric type II SMA treated with nusinersen and to establish possible patterns of treatment effect in relation to different variables such as age, baseline value and SMN2 copy number. Read More

BioDrugs 2021 Jun 7. Epub 2021 Jun 7.

Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry, Edmonton, T6G 2R3, Canada.

The debilitating neuromuscular disorders Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), which harm 1 in 5000 newborn males and 1 in 11,000 newborns, respectively, are marked by progressive muscle wasting among other complications. While DMD causes generalized muscle weakness due to the absence of the dystrophin protein, SMA patients generally face motor neuron degeneration because of the lack of the survival motor neuron (SMN) protein. Many of the most promising therapies for both conditions restore the absent proteins dystrophin and SMN. Read More

J Pediatr Orthop 2021 Jul;41(Suppl 1):S87-S89

Department of Orthopedics, Alfred I. DuPont Hospital for Children, Wilmington, DE.

Background: Children with neuromuscular disorders regularly seek care from pediatric orthopaedic surgeons. These conditions can have a significant impact on the growth and development of children and their function and well-being as adults. Questions exist about the long-term outcomes of musculoskeletal interventions performed during childhood. Read More

Front Neurol 2021 20;12:650535. Epub 2021 May 20.

Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

To determine the safety and tolerability of nusinersen treatment in ambulatory adults with spinal muscular atrophy (SMA) and investigate the treatment effect on muscle strength, physical function, and motor unit physiology. Individuals aged 18 years or older with genetically confirmed 5q SMA, three or more copies of the SMN2 gene, and the ability to ambulate 30 feet were enrolled. Safety outcomes included the number of adverse events and serious adverse events, clinically significant vital sign or laboratory parameter abnormalities. Read More

Brain Dev 2021 Jun 3. Epub 2021 Jun 3.

Department of Pediatrics, Jichi Medical University, Tochigi, Japan. Electronic address:

Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot-Marie-Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. Read More

Lancet Child Adolesc Health 2021 Jul 3;5(7):491-500. Epub 2021 Jun 3.

Biogen, Cambridge, MA, USA.

Background: Nusinersen showed a favourable benefit-risk profile in participants with infantile-onset spinal muscular atrophy at the interim analysis of a phase 2 clinical study. We present the study's final analysis, assessing the efficacy and safety of nusinersen over 3 years.

Methods: This phase 2, open-label, multicentre, dose-escalation study was done in three university hospital sites in the USA and one in Canada. Read More

Neurol Sci 2021 Jun 5. Epub 2021 Jun 5.

Department of Neurology, Department of Neurosciences and Mental Health, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, Avenida Professor Egas Moniz, 1649-035, Lisbon, Portugal.

Neurol Sci 2021 Jun 3. Epub 2021 Jun 3.

Division of Neurology, Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Ermita, 1000, Manila, Philippines.

We report a 51-year-old male diagnosed with X-linked recessive spinal and bulbar muscular atrophy (SBMA) by genetic testing who presented with 30 years history of progressive proximal and bulbar weakness responsive to cholinesterase inhibitor. Although the anti-acetylcholine receptor antibody (anti-AChR Ab) was negative, the myasthenic state was confirmed by decremental response in repetitive nerve stimulation and increased jitter frequency and blocking in single fiber-electromyography. While myasthenia gravis and SBMA may co-exist independently in an individual having the signs and symptoms of both conditions, the absence of anti-AChR Ab may imply that myasthenia can be an exaggerated activity-induced fatigue or weakness from the latter. Read More

Can J Neurol Sci 2021 Jun 4:1-11. Epub 2021 Jun 4.

N Engl J Med 2021 06;384(22):2164-2165

National Institutes of Health, Bethesda, MD

N Engl J Med 2021 Jun;384(22):2164

Istituto per lo Studio, la Prevenzione e la Rete Oncologica, Florence, Italy.

N Engl J Med 2021 Jun;384(22):2163-2164

Lille University Hospital, Lille, France

N Engl J Med 2021 Jun;384(22):2163

Cochin Hospital, Paris, France

Eur J Hum Genet 2021 Jun 1. Epub 2021 Jun 1.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Read More

Int J Mol Sci 2021 May 26;22(11). Epub 2021 May 26.

Neurology IV-Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy.

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Read More

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder leading to paralysis, muscle atrophy, and death. Significant advances in antisense oligonucleotide treatment and gene therapy have made it possible for SMA patients to benefit from improvements in many aspects of the once devastating natural history of the disease. How the depletion of survival motor neuron (SMN) protein, the product of the gene implicated in the disease, leads to the consequent pathogenic changes remains unresolved. Read More

Int J Neonatal Screen 2021 May 23;7(2). Epub 2021 May 23.

New England Newborn Screening Program, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Read More

J Clin Med 2021 May 14;10(10). Epub 2021 May 14.

Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany.

In recent decades, magnetically controlled growing rods (MCGR) were established to treat progressive early-onset scoliosis. The aim of this investigation was to assess the effect of long-term MCGR with continuous distraction on intervertebral discs in scoliotic children. Magnetic resonance imaging (MRI) of 33 children with spinal muscular atrophy was analyzed by grading intervertebral disc degeneration (IDD) and measuring intervertebral disc volume. Read More

Biosensors (Basel) 2021 May 14;11(5). Epub 2021 May 14.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.

Spinal muscular atrophy (SMA) is characterized by severe lethality and irreversible progression. Early diagnosis of SMA is of more practical significance with the emergence of effective therapy. However, existing techniques to identify SMA patients rely on cumbersome instruments, hindering their accessibility and application. Read More

Cells 2021 May 7;10(5). Epub 2021 May 7.

Laboratory of Stem Cell Biology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, Italy.

Methods for the conversion of human induced pluripotent stem cells (hiPSCs) into motor neurons (MNs) have opened to the generation of patient-derived in vitro systems that can be exploited for MN disease modelling. However, the lack of simplified and consistent protocols and the fact that hiPSC-derived MNs are often functionally immature yet limit the opportunity to fully take advantage of this technology, especially in research aimed at revealing the disease phenotypes that are manifested in functionally mature cells. In this study, we present a robust, optimized monolayer procedure to rapidly convert hiPSCs into enriched populations of motor neuron progenitor cells (MNPCs) that can be further amplified to produce a large number of cells to cover many experimental needs. Read More

J Clin Invest 2021 Jun;131(11)

The genetic peripheral neuropathy known as Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive mutations in the FIG4 gene. The transformational success of adeno-associated virus (AAV) gene therapy for spinal muscular atrophy has generated substantial interest in using this approach to create similar treatments for CMT. In this issue of the JCI, Presa et al. Read More

Orphanet J Rare Dis 2021 May 31;16(1):244. Epub 2021 May 31.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Chang Chun Street, Beijing, 100053, People's Republic of China.

Background: Charcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population. Read More