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Introduction
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January 2008 - present
Publications
Publications (160)
Background
Quantitative muscle MRI is one of the most promising biomarkers to detect subclinical disease progression in patients with neuromuscular disorders, including Duchenne muscular dystrophy (DMD). However, its clinical application has been limited partly due to the time-intensive process of manual segmentation.
Objective
We present a simple...
Background
With the approval of disease-modifying treatments for 5q-spinal muscular atrophy (SMA), there is an increasing need for biomarkers for disease course and therapeutic response monitoring. Radially sampled Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA) MR-imaging enables spinal cord (SC) gray matter (GM) delineation and qu...
There has been a wave of new therapeutics in Duchenne muscular dystrophy (DMD) that target the genetic, (missing) protein and flow-on pathogenic mechanisms emerging recently. These medicines will be vital to extend lifespan complementary to corticosteroids, which have been used as a standard of care tool for more than 30 years. While corticosteroid...
Duchenne muscular dystrophy is life-limiting. Cardiomyopathy, which mostly ensues in the second decade of life, is the main cause of death. Treatment options are still limited. The TAMDMD (NCT03354039) trial assessed motor function, muscle strength and structure, laboratory biomarkers, and safety in 79 ambulant boys with genetically confirmed Duche...
Risdiplam is a once-daily oral, survival of motor neuron 2 (SMN2) splicing modifier approved for the treatment of spinal muscular atrophy (SMA). JEWELFISH (NCT03032172) investigated the safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamic (PD) relationship of risdiplam in non-treatment-naïve patients with SMA. JEWELFISH enrolled adul...
New medicines are urgently required to treat the fatal neuromuscular disease, Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 (Nrf2) activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD...
Background: Emerging findings propose that the pathophysiology of migraine may be associated with dysfunctional metabolic mechanisms. Recent findings suggest that migraine attacks are a response to the cerebral energy deficit, and ingestion of ketone bodies stabilizes the generation of a migraine attack. Based on these findings, ketone body supplem...
Emerging evidence suggest migraine is a response to cerebral energy deficiency or oxidative stress in the brain. Beta-hydroxybutyrate (BHB) is likely able to circumvent some of the meta-bolic abnormalities reported in migraine. Exogenous BHB was given to test this assumption and, in this post-hoc analysis, multiple metabolic biomarkers were identif...
New medicines are urgently required to treat the fatal neuromuscular disease, Duchenne muscular dystrophy (DMD). DMD involves progressive muscle damage and weakness, which are preceded by oxidative stress, inflammation, and mitochondrial dysfunction. Dimethyl fumarate (DMF) is a potent small molecule nuclear erythroid 2-related factor 2 (Nrf2) acti...
Metformin (N,N-dimethylguanylguanidine) is one of the most prescribed drugs with pleiotropic, exerted in part by not fully elucidated mechanisms of action. We developed and validated a gas chromatography–mass spectrometry (GC–MS) method for the quantitative analysis of metformin (metformin-d0) in 10-µL aliquots of human serum and urine using N,N-[d...
Objective:
To determine if patients with Post-Polio Syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline.
Methods:
Twenty patients diagnosed with PPS (March of Dimes Criteria) and twenty age- and sex-matched healthy controls (HC) underw...
The Motor Function Measure is a standardized scoring system to evaluate motor function and monitor disease progression in neuromuscular diseases such as Duchenne muscular dystrophy. There are no available reference percentile curves for this measure. The aim of this analysis was to generate Motor Function Measure percentile curves for ambulant and...
Background
Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogen...
Treatment with L-Citrulline in patients with post-polio syndrome: A single center, randomized, double blind, placebo-controlled trial
This single-centered, randomized, double-blind, placebo-controlled study reports the results of L-Citrulline treatment for 24 weeks in patients with post-polio syndrome (PPS). Twenty-nine patients were randomized and...
Background
Pharmacological corticosteroid therapy is the standard of care in Duchenne Muscular Dystrophy (DMD) that aims to control symptoms and slow disease progression through potent anti-inflammatory action. However, a major concern is the significant adverse effects associated with long term-use.
Main
This review discusses the pros and cons of...
Increasing evidence points towards the role of mitochondrial functioning, energy metabolism, and oxidative stress in migraine. However not all previous research has been conclusive and some mitochondrial function/oxidative stress markers have not yet been examined. To this end, alpha-lipoic acid (ALA), total thiols, total plasma antioxidant capacit...
Imbalances in redox homeostasis can result in oxidative stress, which is implicated in various pathological conditions including the fatal neuromuscular disease Duchenne Muscular Dystrophy (DMD). DMD is a complicated disease, with many druggable targets at the cellular and molecular level including calcium-mediated muscle degeneration; mitochondria...
Abstract Background The symptoms of post-polio syndrome (PPS) and its resulting disabilities can affect quality of life and the ability to perform daily activities. No study has comprehensively analysed how various patient-reported outcome measures (PROMs) are associated with objectively assessed physical function in patients with PPS. Aim To inves...
Introduction Increasing evidence points towards the role of mitochondrial functioning, energy metabolism, and oxidative stress in migraine. However not all previous research has been conclusive and some mitochondrial function / oxidative stress markers have not yet been examined.
Methods To this end, alpha-lipoic acid (ALA), total thiols, total pla...
Background:
Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently being tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glu...
Importance
Nitric oxide precursors, such as the amino acid l-arginine and the biguanide antidiabetic drug metformin, have been associated with metabolism and muscle function in patients with Duchenne muscular dystrophy (DMD). The treatment of DMD remains an unmet medical need.
Objective
To evaluate the benefits and harms of a combination of l-citr...
BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocortic...
Cerebral energy deficiency and/or increased oxidative stress decrease the threshold for CSD and activate TRP channels and ASICs, thereby stimulating CGRP and PACAP release. These peptides are pivotal in eliciting the migraine headache and associated symptoms, but we hypothesize that they also induce an antioxidant response and various metabolic cha...
Objective:
This cross-sectional study aimed to assess psychosocial adjustment of children with Duchenne Muscular Dystrophy (DMD) and to explore its possible association to parental stress.
Methods:
34 children with DMD, 9-14.1 years of age, and their parents were included in the study. Caregivers completed the Child Behaviour Checklist (CBCL), t...
Introduction:
The definition of reliable outcome measures is of increasing interest in patients with Duchenne muscular dystrophy (DMD).
Methods:
In this retrospective study we analyzed the longitudinal reliability of clinical and radiological endpoints in 29 ambulant patients with DMD. Clinical outcome measures included motor function measure an...
This cross-sectional study assessed health-related quality of life (HRQOL) in ambulant and nonambulant patients with Duchenne muscular dystrophy, and explored the association between health-related quality of life and clinically assessed motor function. The Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale and PedsQL Neuromuscular mod...
BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocortic...
An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown...
An increasing amount of evidence points towards migraine being a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown...
While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial "Treatment with L-citrulline and m...
The L-arginine/nitric oxide synthase (NOS) pathway is considered to be altered in muscular dystrophy such as Becker muscular dystrophy (BMD). We investigated two pharmacological options aimed to increase nitric oxide (NO) synthesis in 20 male BMD patients (age range 21-44 years): (1) supplementation with L-citrulline (3 × 5 g/d), the precursor of L...
Spinal muscular atrophy (SMA) is a rare genetic and progressively debilitating neuromuscular disease. It is the leading genetic cause of death among infants. In SMA, low levels of survival of motor neuron (SMN) protein lead to motor neuron death and muscle atrophy as the SMN protein is critical to motor neuron survival. SMA is caused by mutations i...
Background
Change in muscle volume and muscle fat fraction are potential non-invasive biomarkers of disease progression in a number of diseases, including sporadic inclusion body myositis¹ and osteoarthritis². Their measurement from magnetic resonance images (MRI) usually involves time consuming manual segmentations of the images by trained readers...
Objective
To validate the precision and accuracy of the semi-automated cord image analyser (Cordial) for lumbar spinal cord (SC) volumetry in 3D T1w MRI data of healthy controls (HC).
Materials and methods
40 3D T1w images of 10 HC (w/m: 6/4; age range: 18–41 years) were acquired at one 3T-scanner in two MRI sessions (time interval 14.9±6.1 days)....
Progressive and irreversible muscle atrophy characterizes Spinal Muscular Atrophy (SMA) and other similar muscle disorder diseases. Objective assessment of muscle functions is an essential and important, although challenging, prerequisite for successful clinical trials. Current clinical rating scales restrain the movement abnormalities to certain p...
The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative mu...
Die Bildgebung, insbesondere die Magnetresonanztomographie (MRT), hat in den letzten Jahren zunehmend an Bedeutung für die Diagnostik angeborener und erworbener Muskelerkrankungen gewonnen. Die Bildgebung ist dabei nicht nur in der Lage, Muskeldegeneration (z. B. fettige Degeneration) zu erfassen und zu quantifizieren, sondern auch sehr frühe Stadi...
Objective
Recent advances in understanding Spinal Muscular Atrophy (SMA) etiopathogenesis prompted development of potent intervention strategies and raised need for sensitive outcome measures capable of assessing disease progression and response to treatment. Several biomarkers have been proposed; nevertheless, no general consensus has been reached...
Background
Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the ac...
Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb mov...
Related data files including raw data files, extracted feature file and demographics.
(ZIP)
Complete analysis report generated by R.
The whole analysis report including additional figures, tables and statistical tools as supplemental material to the main content of this publication is provided in this file.
(PDF)
Source code from prototype game to data analysis.
(ZIP)
An animated replay video of one outlier data file.
(MP4)
Background
High-resolution ultrasonography is a new and promising technique to evaluate peripheral and spinal nerves. Its validity as a diagnostic tool in neurological diseases has been demonstrated in adults. Up to now no reference values have been published in children and adolescents although this technique would be ideal in this population as i...
Background: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. Methods: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. Results: Thirteen patients from 6 non-related families were includ...
Background:
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects 1 in 3500-6000 male births. Despite broad research aiming to improve muscle function as well as heart and brain function, sufficient therapeutic efficacy has not yet been achieved and current therapeutic management is still supportive. In a recent pilot tri...
Purpose of review:
In this update, we describe recent findings on imaging techniques used for the analysis and quantification of affected muscles, advances in pattern recognition, and quantitative muscle imaging in clinical studies.
Recent findings:
Whole-body muscle MRI and meta-analytical approaches, so-called (hierarchical) heat maps of affec...
Becker muscular dystrophy (BMD) has an incidence of 1 in 16 000 male births. This cross-sectional study investigated the relation between validated functional scores and quantitative MRI (qMRI) of thigh muscles in 20 ambulatory BMD patients, aged 18.3-60 years (mean 31.2; SD 11.1). Clinical assessments included the motor function measure (MFM) and...
Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel the...
Study protocol in German.
(PDF)
Study protocol in English.
(PDF)
Background
Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters.
Methods
We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers.
Results
Thirteen patients from 6 non-related families were include...
Focal enlargement of the peripheral and spinal nerves, visualized using high-resolution-ultrasound (HRUS) has been reported in early Guillain-Barré syndrome, but not in the Miller-Fisher-variant. We report the use of HRUS in 2 patients who presented with acute ataxic neuropathy, areflexia, and ophthalmoparesis.
Ultrasound and/or nerve conduction st...
Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date only conventional MRI using visual rating scales is available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: in 3 patients with BMD (mean age 36.8 years)...
We describe a 5-year-old girl with marked hypotonia, poor feeding and reduced facial expression since birth. Congenital myopathy was suspected; muscle biopsy showed unspecific type 1 fibre predominance. The possibility of a ryanodine receptor 1 gene (RYR1)-associated myopathy was considered, but not further investigated. At the age of 2 years, she...
Bei den neuromuskularen Erkrankungen werden – haufig durch einen genetischen Defekt – die Skelettmuskulatur oder die motorischen Nerven geschadigt mit zunehmender Schwache, Verlust der Selbststandigkeit und haufig reduzierter Lebenserwartung. Wahrend fruher nur eine palliative Behandlung moglich war, sind aktuell mehrere Therapien in praklinischen...
In the recent past substantial progress in the genetic assessment and the availability of advanced immuno-histochemical staining techniques formed the beginning of a new era in characterization and classification of inherited muscle disorders. This was even more so since the introduction of imaging—and especially MRI—into routine diagnostic workup...
Muscular dystrophies are a group of inherited diseases mainly affecting skeletal muscles, which result in progressive disability and often end in loss of ambulation and early demise of the patients. While no specific treatments are available to date, multiple promising therapies are under development. Muscle imaging can detect specific patterns of...
Slow channel congenital myasthenic syndrome is caused by a genetically determined kinetic anomaly of the acetylcholine receptor at the neuromuscular junction leading to its prolonged open state. Patients typically present with fatigability and static weakness of neck, hand and finger extensors. The open-channel blockers fluoxetine and quinidine hav...
The aim of this chapter is to provide algorithms based on muscle imaging findings that might be of help for scheduling appropriate genetic testing in patients presenting with clinical and histopathological features consistent with a congenital myopathy, limb-girdle myopathy, or myofibrillar myopathy. As whole-body muscle imaging data are not yet av...
Motor neuron diseases (MNDs) represent a group of neurological diseases characterized by progressive deterioration of the motor neurons in the brain, brain stem, and spinal cord, leading to muscle weakness and wasting. Genetic MND may be caused by mutations in genes that are widely expressed. Although our understanding of the pathophysiology has in...
The effects of aging on muscle tissue—in terms of total and regional muscle mass, muscle fiber size and number—and its clinical consequences with respect to muscle power, strength, and endurance have been investigated extensively during the past few decades. The aging process of striated muscle tissue is based on a complex (patho)physiological mech...
Congenital myopathies (CMs) are a clinically and genetically heterogeneous group of early-onset myopathies that are classified according to the predominant histopathological findings in skeletal muscle. CMs usually exhibit distinctive morphological abnormalities such as rods, an increased number of central nuclei or central or multiple cores. In mo...
Autosomal dominant and recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic diseases with a wide spectrum of clinical involvement and severity. In contrast to the more common X-linked dystrophinopathies, onset is often later during late childhood or at adult age. LGMD patients usually show progressive weakness pred...
Mutations in the serine palmitoyltransferase subunit 1 (SPTLC1) gene are the most common cause of hereditary sensory neuropathy type 1 (HSN1). Here we report the clinical and molecular consequences of a particular mutation (p.S331Y) in SPTLC1affecting a patient with severe, diffuse muscle wasting and hypotonia, prominent distal sensory disturbances...
Neuromuscular imaging has increasingly become an important tool in the detection and diagnosis of inherited and acquired neuromuscular disease. This book is a groundbreaking radiological and neurological overview of current methods and applications of imaging—including aspects of neuroimaging and musculoskeletal imaging—in patients with inherited,...
The preceding chapters in this book focused on the basic principles of imaging modalities (Part I) and muscle anatomy and physiology (Part II). Part III deals with the clinical applications of neuromuscular imaging. Neuromuscular disorders comprise a large, heterogeneous group of diseases of the peripheral nervous system. They include hereditary an...
The second part of this book focuses on the fundamental anatomy of skeletal muscle tissue. It is important to understand the normal microscopic and macroscopic structure of skeletal muscle and the underlying physiological and pathological processes before focusing on distinct neuromuscular disorders.
The purpose of this ethics approved trial was to correlate quantitative MRI with functional abilities in both ambulant and non-ambulant Duchenne muscular dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited. Physical assessment was performed using the motor function measurement (MFM) scale. Axial 3T MRI scans of the thighs...
We examined the influence of a single exercise session on quantitative muscle fat fraction MRI measurements. Ten healthy volunteers were scanned on a 3T body scanner before and after a session of bilateral squats until muscular fatigue. Axial in- and opposed phase images were acquired at a fixed distance from the knee joint and fat fractions were c...
Antecedent surgery has been described to trigger Guillain-Barré syndrome (GBS), but its evidence is poor and based on case reports only.
We performed a retrospective analysis of 63 patients with GBS admitted to the University Hospital Basel and University Children's Hospital Basel from January 2005 to December 2010. We calculated and compared the i...
Array genomic hybridization (AGH) has recently been implemented as a diagnostic tool for the detection of submicroscopic copy number variants (CNVs) in patients with developmental disorders. However, there is no consensus regarding the choice of the platform, the minimal resolution needed and systematic interpretation of CNVs. We report our experie...
Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant muscular dystrophy with late onset and slow progression. The aim of this study was to compare different methods of quantitative MRI in the follow-up of OPMD to semiquantitative evaluation of MRI images and to functional parameters. We examined 8 patients with genetically confirm...
Congenital myopathies are a genetically heterogeneous group of early-onset myopathies classified according to the predominant histopathological findings in skeletal muscle. During the past years, considerable overlap between different pathological and genetic forms of congenital myopathies has been discovered. In contrast, the pattern of involved m...
