#WMS2024
#WMS2024
Professor of Neuromuscular Diseases at Newcastle University in the UK. Interested in basic and clinical research.
How can muscle imaging help in the diagnosis and follow-up of patients with neuromuscular diseases?
Muscle imaging is gaining popularity for both the diagnosis and follow-up of patients with neuromuscular diseases. In this lecture, I will review the different options available for obtaining images of the skeletal muscles of patients, including ultrasound (US) and MRI. I will discuss the pros and cons of both techniques, review the main radiologic features of different neuromuscular diseases and walk you through the scientific evidences on the utility of these techniques for the follow-up of patients in clinics, trials and natural history studies.
Coordinator of the ERN EURO-NMD since 2018 and co-coordinator from 2016 to 2017. Key Expertise: Board-certified neurologist and neuropathologist with long-standing clinical and research expertise in neuromuscular disorders. Expertise in rare disease policies.
Muscle biopsy assessment
During this talk, we will discuss the basics of muscle biopsy analysis and possible future applications. We will consider pre and post-muscle biopsy aspects that allow us to achieve the best diagnostic yield. We will consider the best practices to perform the biopsy, which techniques can be used, and what can be learnt from it. We will discuss how to read a muscle biopsy considering the normal aspects of muscle and the common pathological changes using for this some clinical cases as examples. Muscle biopsy has been part of the diagnostic workup in patients with neuromuscular diseases since the 1960s. Although diagnostic algorithms for some muscle diseases have changed with the advances in genomics, we will discuss how muscle biopsy can evolve and be part of this new era.
Dr. A. Reghan Foley is a Senior Research Physician within the Neuromuscular and Neurogenetic Disorders of Childhood Section, NINDS, National Institutes of Health, Bethesda, Maryland, USA. She sees genetically undiagnosed patients with congenital onset neuromuscular conditions and follows children with congenital myopathies and congenital muscular dystrophies via various natural history studies. Dr. Foley has served as an investigator for Phase 1 clinical trials in the COL6-related dystrophies, LAMA2-related dystrophies, MTM1-related myopathy, and giant axonal neuropathy. She has been involved in gene discovery efforts in congenital and childhood neuromuscular disorders, via the UK10K Consortium and via a collaboration with the Broad Institute’s Center for Mendelian Genomics.
Systematic overview of patients presenting with “floppy infant” syndrome with neuromuscular weakness
Hypotonia in an infant or the so-called “floppy infant” syndrome has numerous potential etiologies, including genetic or acquired causes affecting the central nervous system or the peripheral nervous system. An essential goal of the neuromuscular specialist is to determine if the hypotonic infant has underlying weakness, the pattern of such weakness, and any associated general examination findings of diagnostic relevance. Along with detailed clinical history and family history and a careful neuromuscular examination of the infant (and often the parents), the use of ancillary tools including muscle ultrasound and electromyography/nerve conduction studies may help in localising the cause of weakness to the motor neuron, the nerve, the neuromuscular junction or the muscle. This talk reviews the approach to evaluating infants with hypotonia due to neuromuscular weakness, outlines extensive differential diagnoses, and highlights clinical pearls helpful for recognizing specific congenital myopathies, congenital muscular dystrophies, and congenital myasthenic syndromes. While the availability of next generation sequencing (NGS) in the clinical setting may alter the traditional diagnostic approach to the so-called “floppy infant,” the role of the neuromuscular specialist remains paramount for establishing a differential diagnosis and assessing which gene variants found via NGS are plausible or implausible based on the patient’s overall phenotype, which is essential for arriving at an accurate diagnosis and providing disease-relevant proactive care.
Assoc. Prof. Jana Haberlová MD, Ph.D. is a paediatric neurologist, Head of Neuromuscular Centre and Deputy Head of Department of Pediatric Neurology in Motol University Hospital in Prague, Czech Republic. Jana was trained as an adult neurologist and has now been working for 25 years as a paediatric neurologist and electrophysiologist. For the last 15 years, she has mainly focused on neuromuscular disorders in children. During her training, she underwent repeated short-stay visits to the MRC Centre for Neuromuscular Diseases in London, and for one year, she worked at the John Walton Muscular Dystrophy Research Centre at Newcastle University. Upon her return, she established the Neuromuscular Centre for Children at Motol University Hospital in Prague.
She is involved in clinical research and clinical trials with new therapies, particularly in DMD and SMA. She is a member of the Czech Paediatric Neurology Society and the WMS.
Gait pattern in infants
In the talk, the types of gait during the first six years of life will be covered. During this period, the gait is influenced not only by typical neurological syndromic abnormality patterns like in adulthood, but by developmental factors as well. Short videos of myopathic, neuropathic, motor neuron disease, spastic, atactic, choreatic, or patients with behavioural abnormality problems will be presented. In the end, the basic differential diagnosis and examination algorithm will be covered.
Specialist in neurology, pediatric neurology and clinical neurophysiology. Her professional activities focus on neuromuscular disorders in children and adults. She is a Board Member of Polish Neurological Society and a vice-president of Polish Society of Paediatric Neurology, serves as an expert for implementation of National Plan for Rare Diseases.
EMG and Neurography examination
EMG and neurography (nerve conduction studies, NCS) are an extension of the clinical evaluation of the patient with neuromuscular disease (NMD). EMG and NCS allow to define the level of the lesion of the motor unit, the activity and distribution of the process (chronic vs acute, local vs. generalized) and, if necessary, can be used to monitor disease progression. Some test, such as motor unit number estimate (MUNE), or CMAP amplitudes are used as inclusion criteria or outcome measures for clinical trials. Repetitive nerve stimulation test and SFEMG play major role in the diagnosis of the neuromuscular junction diseases. Appropriate reference values have to be used when testing children and adults. Improved access to genetic testing changed diagnostic algorithms of the most common NMDs, such as eg. DMD, SMA or DM1, in which EMG and NCS are no longer needed for the diagnosis. At the same time new NCS diagnostic criteria for inflammatory neuropathies have been proposed. EMG and NCS are indispensable in the diagnosis of acquired NMDs, with an implementation of the current diagnostic criteria. In many hereditary NMDs EMG and NCS will be performed not at the beginning of the evaluation, but as a tool to characterize the phenotype of the patient and aid the interpretation of NGS or WES testing. The examples of the challenges in EMG and NCS will be provided and discussed with the workshop participants.
Associate Professor of Neurology, Department of Neurosciences; Chief of the Neuromuscular Unit at the University Hospital Città della Salute di Torino, Italy; Responsible of the diagnostic and care services for neuromuscular disorders, Regional referral level (Nord-West Italy); Laboratory for Neuromuscular Diseases; PI in observational research projects and therapeutic trials. Coordinator of the HCP Città della Salute – EURO NMD
Swallowing weakness
Dysphagia, defined as a disorder of deglutition with impaired swallowing, is a common complication in several neuromuscular disorders (NMDs), and represents a life-threatening event when not timely recognized and treated.
The deglutition process is divided in: oral phase, including preparatory and transit subphases, when food is chewed and mobilised into the oropharynx; it requires appropriate sensation and coordination of tongue, soft and hard palate, and adequate masticatory and mimic voluntary muscles functioning; pharyngeal phase, when the bolus passes through the palatoglossal arch and the upper esophageal sphincter (UES) under involuntary muscles control, to protect the airways from aspiration; and esophageal phase, when the food bolus passes the UES and goes into the stomach by the smooth muscles peristalsis.
A physiologic deglutition process matures after the sixth month of life and requires the integrity of bulbar anatomic systems, including motor neurons, cranial nerves, skeletal and smooth muscles. Swallowing impairment differs considerably in NMDs according to their etiology, in terms of clinical presentation, therapeutic options, and prognosis. Typical symptoms include poor handling of the oral bolus, upper laryngeal penetration, aspiration and choking. Complications include ab ingestis pneumonia, dehydration, and weight loss in already fragile patients.
Recent general recommendations to manage dysphagia suggest a multidisciplinary approach with a tailored treatment plan involving dietary modification, rehabilitation, and, in selected cases, a surgical approach. Specific guidelines are only available for SMA and ALS; more defined, disease-specific protocols for evaluation and training of neuromuscular dysphagia are auspicated, to reduce delayed diagnoses and treatment.
Dr Ravenscroft is an NHMRC Emerging Leadership Fellow at UWA and leads the Rare Disease Genetics and Functional Genomics Group at the Harry Perkins Institute.
Genetic assessment
Increasingly, genetic testing is becoming a frontline tool in the diagnosis of patients that present with neuromuscular diseases. Massively parallel sequencing, new informatic tools and optical genomic mapping is ushering in a new era in molecular diagnostics for neuromuscular diseases and novel disease gene discovery. Unbiased screening has resulted in blurring of the boundaries between different entities and expanding phenotypes associated with variants in a given gene. In this presentation A/Prof Gina Ravenscroft will discuss when to consider genetic testing, different types of genetic testing available and the value of clinical details and routine work-up in guiding molecular diagnoses. Through illustrative examples, A/Prof Ravenscroft will explore the role of genetics in neuromuscular diseases and the various considerations needed along the way to reaching a timely and accurate genetic diagnosis. Drawing on her research experience, A/Prof Ravenscroft will also discuss synergies across diagnostic and research centres and the benefits of an integrated diagnostic-research team.
Research Interest: Through a combination of state-of-art methods and a large network of international collaborators, the recently set up Savarese group aims to dissect the molecular mechanisms underlying the often-observed discordance between the identified genotype and the expected phenotype in patients with neuromuscular diseases, a class of diseases affecting muscular function. https://www.folkhalsan.fi/en/knowledge/research/genetics/group-savarese/
Distal weakness
Distal myopathies are primary muscles diseases due to mutations in over 20 genes. The clinical presentation at the onset includes a weakness of the muscles of the forearm, hands, lower leg or feet. However, the age of onset, clinical presentation, disease progression, muscle involvement, and histological findings are extremely variable.
An increasing number of genes and variants associated with a distal myopathy have been recently identified. Moreover, different variants in the same gene may cause either dominant or recessive forms. Currently, we are without a comprehensive understanding of the genotype-phenotype correlations.
We will cover the genetic and clinical features of distal myopathies, highlighting the most recently identified forms. We will also review their pathomechanisms and the current steps towards a diagnosis, using the most advanced methodologies. Finally, we will discuss the main technical and interpretative challenges.
Benedikt Schoser is a trained neurologist, neurophysiologist, neurointensivist, palliative medicine doctor. He is a professor of Neurology, at the Friedrich-Baur-Institute, LMU Munich, Germany. He is a long-term member of the WMS organizes the WMS teaching course, and is a member of the WMS executive board. Benedikt's special interests are multisystemic neuromuscular disorders, translational research.
How to assess adults
I will summarize a clinical Gestalt approach for assessing adults living with neuromuscular disorders. The German word ‘Gestalt’ means pattern, structure, configuration, or shape. In the early 1900s, the so-called Berlin School of Gestalt psychology developed a more profound concept of human perception based on the five Gestalt principles: Proximity, Similarity, Continuity, Closure, and Connectedness.
Today, designers use these principles to organize content for visually pleasing and ease of understanding, for example, for web content Gestalt approach is a theory on transforming clinical perceptions into coherent, integrative holistic constructs, a significant difference from phenotyping. Gestalt implies that a clinician has the learned skill to brand clinical indirect decisions without complete information by generating solutions from generalizations. We describe this pattern recognition as a heuristic approach to decision-making. Knowledge and experience sustain top-down decision-making accuracy as experienced clinicians have better pattern recognition skills. The Classic Gestalt approach is quick and straightforward but requires much practice. My talk will help to start this type of approach.
Main fields of research are faciocapulohumeral dystrophy (FSHD) and congenital myopathies.
Limb girdle weakness
In patients presenting with limb girdle weakness, there is a wide range of inherited and acquired diagnosis that should be considered.
Limb-girdle muscular dystrophy is the first group consisting of inherited disorders with progressive weakness of muscles around the hips and shoulder, leading to a loss of muscle strength and bulk over a number of years. Onset may occur in childhood, adolescence, young adulthood, or even later. Helpful clinical features that help to differentiate the > 20 subtypes include: predominant upper girdle weakness, disproportionate respiratory muscle involvement, distal weakness, hip adductor weakness, calf hypertrophy, contractures and cardiac involvement. Other genetic myopathies presenting with limb girdle weakness are (late-onset) Pompe disease, facioscapulohumeral muscular dystrophy and Becker muscular dystrophy. While there are no treatments which directly reverse the muscle weakness associated with these inherited condition, supportive treatment can decrease the complications.
The second large group of causes of limb girdle weakness are acquired myopathies, including inflammatory myopathies, toxic myopathies and myopathies caused by endocrine disturbances. In elderly patients, there is often a combination of acquired causes leading to gradually progressive limb girdle weakness.
Finally, a number of non-myopathic causes should be considered, including auto-immune neuromuscular junction disorders (Lambert-Eaton myasthenic syndrome) and plexopathies (neuralgic amyotrophy), motor neuron diseases and peripheral nerve diseases (such as CIDP_ The disease course and pattern of additional symptoms (sensory disturbance, hyperreflexia) are important clues to the localization and etiology. The treatment possibilities of these two latter groups depend on the specific etiology.
Stanislav Voháňka has long been involved in the field of neuromuscular diseases and he is the head of the Neuromuscular Centre at the Department of Neurology of the University Hospital in Brno. In this area he is focused on myasthenia gravis, inflammatory myopathies, hereditary muscle diseases, and electromyography. He is the chairman- elected of the Czech Neuromuscular Society and administrator of the national neuromuscular registries.
Neuromuscular fatigue
Skeletal muscle fatigue or fatigability is a key symptom of neuromuscular transmission disorders. Correct diagnosis is based on knowledge of the characteristic clinical manifestation. Signs and symptoms fluctuate depending on physical activity, disappearing after rest. Worsening in the afternoon and evening is typical. The most affected muscles are ocular (asymmetric ptosis, diplopia), bulbar (swallowing and speech disorders), proximal and axial muscles (inability to elevate upper limbs, head drop). It could be disclosed with specific tests for endurance and repetition of movements. The aim of this session is to provide an overview of the main symptoms and targeted examination of these disorders.
Karim Wahbi is Professor of Cardiology at the University of Paris, France and head of the reference centre for neuromuscular cardiomyopathies in Cochin Hospital, Paris. He completed his cardiology internship and residency at the University of Paris Descartes. He specialises in the clinical management of patients with cardiomyopathies with a specific expertise in neuromuscular diseases. Key areas of clinical and fundamental research for Pr. Wahbi are prevention of heart failure and sudden death and the study of molecular mechanisms underlying neuromuscular cardiomyopathies.
Heart involvement
Heart involvement is very common in patients with neuromuscular conditions, genetic and inflammatory, and has a major impact on patient quality of life and vital prognosis. This course will summarize the main clinical features, impact on prognosis and therapeutic approaches for neuromuscular cardiomyopathies, including DM1, dystrophinopathies, laminopathies, and other conditions at high cardiac risk.
Neurologist, neurophysiologist and doctor for palliative care at the Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University Munich, Germany. Experience in intensive care and rehabilitative neurological medicine. Research mainly in myotonic dystrophies, glycogen storage diseases and myasthenia gravis. Medical qualification 2004 and Dissertation 2005 at the Technical University of Munich, Diploma in Health Economics 2005 in the Switzerland, Emergency Medicine 2009 in Munich; Neurologist 2012 and palliative care 2019 in Munich, Germany.
Ventilatory weakness
Dysfunction of the respiratory system typically causes hypercapnic and hypoxic respiratory failure with variability in degree, progression, and clinical symptoms. In contrast to lung diseases with altered perfusion and/or diffusion, most neurological conditions affecting ventilation are caused by an impaired breathing pattern and/or insufficient respiratory muscle pump function, which results in acute, chronic, or acute-on-chronic hypercapnia at first and hypoxemia at later stages. Thus, for an early and correct diagnosis and sufficient treatment, knowledge of the origin of hypoventilation is essential. Depending on the disease, respiratory dysfunction can occur on one or more levels: central neurons including the upper motor neuron and specialised respiratory pacemaker neurons, lower motor neurons, peripheral motor nerves, the neuromuscular junction, thoracic compliance including skeletal deformities, and the muscle itself. The Pre-WMS teaching course on respiratory weakness will highlight typical neuromuscular disorders with respiratory impairment, recommended diagnostics, and treatment.
