Review
Clinical Neurology
Emma Matthews, Jacqueline Palace, Sithara Ramdas, Valeria Sansone, Martin Tristani-Firouzi, Savine Vicart, Tracey Willis
Summary: Significant progress has been made in the field of pediatric skeletal muscle channelopathies, leading to a broader understanding of clinical presentations and new phenotypes. However, there is a lack of data on epidemiology, natural history, and treatment efficacy, resulting in a lack of best practice care recommendations. Holistic management, including addressing work, education, activity, and additional symptoms, is important, and there is an urgent need for high-quality data on prevalence, burden, and optimal treatment.
PEDIATRIC NEUROLOGY
(2023)
Article
Clinical Neurology
Chad Heatwole, Elizabeth Luebbe, Spencer Rosero, Katy Eichinger, William Martens, James Hilbert, Jeanne Dekdebrun, Nuran Dilek, Christine Zizzi, Nicholas Johnson, Araya Puwanant, Rabi Tawil, Giovanni Schifitto, Christopher A. Beck, J. Franklin Richeson, Wojciech Zareba, Charles Thornton, Michael P. McDermott, Richard Moxley
Summary: Mexiletine did not significantly affect 6-minute walk distance in patients with DM1, but did improve hand grip myotonia. Adverse events and cardiac conduction measures were similar between the mexiletine and placebo groups.
Review
Clinical Neurology
Felix Kleefeld, Benedikt Schoser
Summary: DM2 is a genetic disorder characterized by progressive muscle weakness, wasting, and muscle pain, and it can also affect other organ systems. This review provides an updated overview on the research literature on DM2, with a focus on the management of multisystemic involvement and atypical clinical phenotypes.
CURRENT OPINION IN NEUROLOGY
(2023)
Article
Clinical Neurology
Vinojini Vivekanandam, Rebecca Ellmers, Dipa Jayaseelan, Henry Houlden, Roope Mannikko, Michael G. Hanna
Summary: Accurately determining the pathogenicity of uncertain missense genetic variants is a challenge for clinical use of genetic data. In this study, nine in silico predictive tools were compared with cell-based electrophysiology for CLCN1 variants related to myotonia congenita. Most tools showed poor accuracy, with MutationTaster and REVEL having the highest accuracy but poor specificity. Combining methods improved overall performance but lacked specificity. The current predictive tools for this chloride channel are unreliable, and better tools are urgently needed. Improving predictive tool accuracy is a wider challenge for genetic data implementation.
Article
Clinical Neurology
Noemi Vereb, Federica Montagnese, Dieter Glaeser, Benedikt Schoser
Summary: This study reveals a relevant clinical overlap between NDM-CLCN1 and NDM-SCN4A patients, highlighting the importance of early and broad genetic investigation for precise identification of the NDM subtype. Despite the clinical and genetic heterogeneity, the limited response to current anti-myotonic drugs remains a continuing challenge.
JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Michela De Bellis, Brigida Boccanegra, Alessandro Giovanni Cerchiara, Paola Imbrici, Annamaria De Luca
Summary: Voltage-gated sodium channels are an important target for drug discovery and are involved in various physiological processes. Blockers of these channels are clinically used in several excitability disorders, including myotonia. However, current treatments are not selective for the specific sodium channel isoform involved in myotonia, highlighting the need for developing more potent and use-dependent drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Serena Pagliarani, Giovanni Meola, Melania Filareti, Giacomo Pietro Comi, Sabrina Lucchiari
Summary: Non-dystrophic myotonias (NDM) are a group of disorders involving chloride and sodium channels. This article presents a case of a woman with coexisting sodium and chloride channelopathies, leading to a complex phenotype with features of both myotonia congenita (MC) and paramyotonia congenita (PMC). The proper identification of signs and symptoms by an expert neurologist is crucial for accurate diagnosis and appropriate therapy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Vukan Ivanovic, Stojan Peric, Jovan Pesovic, Radoje Tubic, Ivo Bozovic, Ivana Petrovic Djordjevic, Dusanka Savic-Pavicevic, Giovanni Meola, Vidosava Rakocevic-Stojanovic
Summary: The study aims to determine the most indicative symptoms, signs, and diagnostic findings in patients referred to neurological outpatient units for suspicion of DM2. An easy-to-administer DM2 early diagnosis score (DM2-EDS) was developed for early diagnosis of DM2.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Shinichiro Yamada, Atsushi Hashizume, Yasuhiro Hijikata, Tomonori Inagaki, Daisuke Ito, Yoshiyuki Kishimoto, Fumie Kinoshita, Akihiro Hirakawa, Shinobu Shimizu, Tomohiko Nakamura, Masahisa Katsuno
Summary: This study investigated the effect of cold exposure on patients with spinal and bulbar muscular atrophy (SBMA). The results showed that cold paresis was common in SBMA and correlated with the prolongation of distal latency. A clinical trial found that mexiletine did not restore cold exposure-induced prolongation of distal latency, but improved tongue pressure and grip strength under cold exposure. The study emphasizes the importance of understanding and managing cold-related symptoms in SBMA patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maggie Lutz, Miranda Levanti, Rebekah Karns, Genevieve Gourdon, Diana Lindquist, Nikolai A. Timchenko, Lubov Timchenko
Summary: Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease caused by toxic RNA with expanded CUG repeats. Correction of the GSK3 beta-CUGBP1 pathway using the GSK3 inhibitor tideglusib (TG) has shown benefits in DM1 mice. TG treatments corrected the expression of genes involved in cell transport, development, and differentiation, as well as the key trigger of myotonia in DM1. Dysregulated CUGBP1 contributes to the toxicity of expanded CUG repeats and affects gene expression and CNS abnormalities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Veterinary Sciences
Christian Woelfel, Kathryn Meurs, Steven Friedenberg, Nicole DeBruyne, Natasha J. Olby
Summary: This is a case of a 10-month-old castrated male cat with episodic limb rigidity, hypertrophied musculature, and other symptoms. Electromyography and whole genome sequencing identified a mutation in the CLCN1 gene causing myotonic discharges. Treatment with phenytoin resulted in long-term improvement.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2022)
Article
Clinical Neurology
Vinojini Vivekanandam, Karen Seutterlin, Emma Matthews, John Thornton, Dipa Jayaseelan, Sachit Shah, Jasper M. Morrow, Tarek Yousry, Michael G. Hanna
Summary: This study performed muscle MRI in patients with periodic paralyses and correlated it with clinical features. The results showed intramuscular fat accumulation in the muscles of patients with periodic paralysis, which may be helpful in detecting early muscle involvement. The study highlights the importance of muscle MRI as a potential biomarker in assessing disease progression and in clinical trials.
Article
Biochemistry & Molecular Biology
Sarah U. Morton, Christopher R. Sefton, Huanqing Zhang, Manhong Dai, David L. Turner, Michael D. Uhler, Pankaj B. Agrawal
Summary: miRNAs play a key role in regulating mRNA during processes like muscle differentiation. Understanding miRNA targets can provide insights into muscle biology and gene expression changes caused by diseases. The study found that differentially expressed miRNAs are enriched for functions related to calcium signaling and sarcomere formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Christina Mousele, Emma Matthews, Robert D. S. Pitceathly, Michael G. Hanna, Susan MacDonald, Konstantinos Savvatis, Aisling Carr, Christopher Turner
Summary: This retrospective study evaluated patients with myotonic dystrophy receiving mexiletine, showing that 96% of patients reported improvement in myotonia symptoms with long-term use of mexiletine, and no clinically relevant cardiac adverse events were associated with the treatment.
NEUROLOGY-CLINICAL PRACTICE
(2021)
Article
Clinical Neurology
Sakhaa Hanoun, Yuyao Sun, Farzad Ebrahimi, Mehdi Ghasemi
Summary: Myotonic dystrophy (DM) is a neuromuscular disease that can cause speech and language abnormalities related to cognitive dysfunction, muscle weakness, and myotonia. Understanding these abnormalities can provide markers for disease characterization and evaluation.
JOURNAL OF CLINICAL NEUROSCIENCE
(2022)
Article
Rehabilitation
Gang Liu, Bradley Chi
Summary: This article provides a comprehensive review of the technological advances in the diagnosis and treatment of patients with a disorder of consciousness over the past 10 years. While these advances show promise, there is limited high-quality evidence supporting their widespread clinical adoption.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Amy Shapiro-Rosenbaum, Michelle P. Jaffe
Summary: Caregivers of persons with DoC experience high levels of perceived burden, which is associated with adverse physical, emotional, psychosocial, and financial outcomes and is directly tied to expressed needs for information and support. Providing individualized education and training at each phase of recovery can enhance effective communication between providers and caregivers, helping to increase caregiver proficiency in managing their loved one's care while also helping to mitigate the challenges associated with perceived burden. This may subsequently increase the rate of community discharge among persons with DoC, potentially translating to a reduction in the long-term costs of care for this population.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Jean E. Woo, Abana Azariah, Eboni A. Reed, Nicholas Gut
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Katherine O'Brien, Bei Zhang, Elizabeth Anderl, Sunil Kothari
Summary: Behavioral assessment is essential in the clinical evaluation of disorders of consciousness, and it should be supplemented by qualitative behavioral observations and individualized quantitative assessments. Therapy disciplines, staff, and family members all play important roles in this process.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Mary E. Russell, Cindy B. Ivanhoe, Eboni A. Reed
Summary: Acquired brain injury, especially severe brain injury, is a chronic medical condition that lacks research studies on postacute care and long-term outcomes. There is a need for standardized admission criteria, diagnostic tools, and prognostic protocols. Furthermore, healthcare systems should consider personalized factors and different perspectives on meaningful recovery and quality of life.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Brooke Murtaugh, Susan Fager, Tabatha Sorenson
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Amanda Appel, Eric Spier
Summary: This article discusses the importance of the emergence of consciousness in brain-injured patients and presents a framework for evaluating and tailoring treatment of sleep and pain. Although more research is needed, validated tools are currently available for assessing consciousness, pain, and sleep.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Kristen A. Harris, Yi Zhou, Stacey Jou, Brian D. Greenwald
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Ruth Tangonan, Christos Lazaridis
Summary: Acute disorders of consciousness refer to impairments in arousal and awareness that occur within 28 days of an initial injury, which can be caused by various insults. Thorough evaluations, including assessments of consciousness level, brainstem reflexes, and motor responses, are important. Laboratory tests, imaging, and electrophysiology testing are needed for the evaluation of acute disorders of consciousness. Prognostication in this phase should be done cautiously, with open and frequent communication with families, considering the significant multidimensional uncertainty.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Editorial Material
Rehabilitation
Sunil Kothari, Bei Zhang
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Michael H. Marino
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Linda B. Xu, Stephen Hampton, David Fischer
Summary: Neuroimaging in DoC has evolved to characterize complex brain networks and may have significant implications for understanding the natural history of DoC and optimizing long-term management.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
David B. Arciniegas, Lindsey J. Gurin, Bei Zhang
Summary: Understanding the neuroanatomy of wakefulness and awareness is crucial for clinicians dealing with disorders of consciousness. Wakefulness is supported by brainstem-forebrain-diencephalic systems, while awareness is a result of integrated activity within and between wakefulness systems and cortical areas. Disruptions in these neural systems can inform the clinical presentation and treatment options for disorders of consciousness.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Katherine Golden, Yelena G. Bodien, Joseph T. Giacino
Summary: This article discusses the classification associated with the four major disorders of consciousness (DoC): coma, vegetative state or unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state. The history of each disorder are briefly reviewed and operational definitions and diagnostic criteria are provided. The article heavily relies on recently released practice guidelines and identifies knowledge gaps and discusses future directions to advance DoC research and practice.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Beth S. Slomine, Stacy J. Suskauer
Summary: Research on children with disorders of consciousness (DoC) lags behind adult literature, and there is a lack of rigorous evaluation of assessment tools for this population. However, recent developments show promise in improving assessment for young children and those without overt command following. Early signs of consciousness are associated with better long-term outcomes. Although large clinical trials are lacking, programmatic data provide valuable information for standards of care and treatment options for children with DoC.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)