Lawrence Korngut

Lawrence Korngut
The University of Calgary | HBI · Department of Clinical Neurosciences

MD MSc FRCPC CSCN(EMG)

About

110
Publications
20,375
Reads
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2,114
Citations
Introduction
Neurologist, Electrophysiologist, Clinical Trialist, Calgary Neuromuscular Clinic Director, Calgary Neuromuscular Program Chair, Canadian Neuromuscular Diseases Network National Principal Investigator, Canadian Neuromuscular Disease Registry Former Chair of Medical and Scientific Advisory Committee, Muscular Dystrophy Canada Director, Calgary ALS and Motor Neuron Disease Clinic
Additional affiliations
August 2009 - September 2015
The University of Calgary
Position
  • Research Assistant
August 2007 - June 2009
The University of Calgary
Position
  • Neuromuscular Fellow
Description
  • Completed a two year neuromuscular disease clinical and basic research fellowship. My research focused on heat shock protein 27 as a protective factor against progression of diabetic polyneuropathy in a mouse model.
July 2002 - June 2007
The University of Western Ontario
Position
  • Neurology Resident

Publications

Publications (110)
Article
Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder characterized by progressive degeneration of upper motor neurons and lower motor neurons, and frontotemporal regions resulting in impaired bulbar, limb, and cognitive function. Magnetic resonance imaging studies have reported cortical and subcortical brain involvement i...
Article
Introduction/aims: Consensus criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast consensus criteria are intended to simplify use and increase sensitivity. We aimed to evaluate the potential impact of those criteria on clinical trial eligibil...
Article
Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. Methods: Participants were at least 18 years old and had FSHD1/F...
Article
Objective: Amyotrophic lateral sclerosis (ALS) is a multi-system disorder characterized primarily by motor neuron degeneration, but may be accompanied by cognitive dysfunction. Statistically appropriate criteria for establishing cognitive impairment (CI) in ALS are lacking. We evaluate quantile regression (QR), that accounts for age and education,...
Article
Full-text available
Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three-dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1-weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging C...
Article
Background: Spinal muscular atrophy (SMA) is the leading genetic cause of infant death and the second most common autosomal recessive disorder; the majority of cases are due to homozygous deletion of SMN1 gene. Methods: This study uses the Canadian Paediatric Surveillance Program to determine the minimum annual incidence of 5q-SMA from birth to 18...
Article
Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people wit...
Article
Background: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enha...
Article
Full-text available
Objective Spinobulbar muscular atrophy (SBMA) is an X-linked adult-onset neuromuscular disorder that causes progressive weakness and androgen insensitivity in hemizygous males. This condition is reported to be extremely rare, but has higher prevalence in certain populations due to multiple founder effects. Anecdotal observations of a higher prevale...
Article
OBJECTIVE To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in N -acetylaspartate (NAA) ratios in the motor and prefrontal cortex within clinical subgroups of ALS. METHODS Seventy-six ALS patients and 59 healthy controls were enrolled in a prospective, longitudinal, multicenter study in t...
Article
Full-text available
Cognitive impairment is now recognized in a subset of patients with amyotrophic lateral sclerosis (ALS). The objective of the study was to identify group differences and neuroanatomical correlates of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in participants ALS. Fifty-three ALS patients and 43 healthy controls recruited as a part of...
Article
Full-text available
Background: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM)...
Preprint
Full-text available
Importance Amyotrophic lateral sclerosis (ALS) is a multi-system disorder characterized primarily by motor neuron degeneration, but may be accompanied by cognitive dysfunction. Statistically appropriate criteria for establishing cognitive impairment (CI) in ALS are lacking. Objective Define thresholds for CI in ALS using quantile regression (QR) t...
Article
Background Wild-type transthyretin amyloidosis (wtATTR) is an important cause of heart failure (HF); however, the prevalence and clinical significance of neurologic complications remains uncertain. Methods This analysis reports findings from a single-centre experience of routine neuropathy screening at the time of wtATTR diagnosis by nerve conduct...
Article
Full-text available
Background: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a re...
Article
Full-text available
Objective: To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatme...
Article
Full-text available
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is characterized primarily by motor neuron but also frontotemporal lobar degeneration. Although the cerebellum is involved in both motor and cognitive functions, little is known of its role in ALS. We targeted the dentate nucleus (DN) in the cerebellum and the associated white matter fibers tracts connecting the...
Article
Response to provincial governments’ decisions regarding monitoring for adults with Spinal Muscular Atrophy - Victoria L Hodgkinson, Kristine Chapman, Aaron Izenberg, Hanns Lochmüller, Colleen O’Connell, Erin K O’Ferrall, Maryam Oskoui, Gerald Pfeffer, Stephanie Plamondon, Xavier Rodrigue, Christen Shoesmith, Jodi Warman-Chardon, Bernard Brais, Lawr...
Preprint
Full-text available
Background Amyotrophic lateral sclerosis (ALS) is a disabling and rapidly progressive neurodegenerative disorder. Increasing age is an important risk factor for developing ALS, thus the societal impact of this devastating disease will become more profound as the population ages. A significant hurdle to finding effective treatment has been an inabil...
Article
Full-text available
Objective To evaluate progressive white matter (WM) degeneration in ALS. Methods Sixty-six patients with ALS and 43 healthy controls were enrolled in a prospective, longitudinal, multicentre study in the Canadian ALS Neuroimaging Consortium (CALSNIC). Participants underwent a harmonized neuroimaging protocol across 4 centres including diffusion te...
Article
Full-text available
Background: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials we...
Article
Full-text available
Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by a preferential involvement of both upper and lower motor neurons. Evidence from neuroimaging and post-mortem studies confirms additional involvement of brain regions extending beyond the motor cortex. The aim of this study was to assess the extent of cerebral disease in a...
Poster
Background: ACE-083 is a locally acting muscle therapeutic based on follistatin that binds myostatin and other muscle regulators. ACE-083 has been shown to increase muscle mass of injected muscles in animal models, healthy subjects, and patients with FSHD or Charcot-Marie-Tooth (CMT) disease. Objectives/Methods: The primary objectives were to dete...
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a preferential involvement of both upper and lower motor neurons. Evidence from neuroimaging and post-mortem studies confirms additional involvement of brain regions extending beyond the motor cortex. The aim of this study was to assess the extent of cerebral diseas...
Article
Objective: The use of speech measures is becoming a common practice in the assessment of bulbar disease progression in amyotrophic lateral sclerosis (ALS). This study aimed to establish psychometric properties (e.g. reliability, validity, sensitivity, specificity) of speech and pause timing measures during a standardized passage. Methods: A large n...
Article
Full-text available
The original version of this article [1] unfortunately included an error to an author’s name. Author Jordi Díaz-Manera was erroneously presented as Jorge Alberto Diaz Manera. The correct author name has been included in the author list of this Correction article.
Article
Gradient-based texture analysis methods have become popular in computer vision and image processing and has many applications including medical image analysis. This motivates us to develop a texture feature extraction method to discriminate Amyotrophic Lateral Sclerosis (ALS) patients from controls. But, the lack of data in ALS research is a major...
Article
Background: We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS). Methods: We prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Co...
Article
Full-text available
Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing p...
Article
Registries are an important platform to which persons with dementia and other cognitive impairments can contribute to research studies. Registries also provide an opportunity for patients to stay informed about current studies. Engaging patients in registry development can increase sustainability of a registry and patient retention in clinical regi...
Article
Full-text available
Background: Myotonic Dystrophy is the most common form of muscular dystrophy in adults, affecting an estimated 10 per 100,000 people. It is a multisystemic disorder affecting multiple generations with increasing severity. There are currently no licenced therapies to reverse, slow down or cure its symptoms. In 2009 TREAT-NMD (a global alliance with...
Article
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Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada...
Article
Full-text available
Response to the Canadian Agency for Drugs and Technologies in Health and Institut national d’excellence en santé et en services sociaux decision regarding nusinersen for Spinal Muscular Atrophy - Craig Campbell, Kathy Selby, Hugh McMillan, Jiri Vajsar, Lawrence Korngut, Bernard Brais, Alex MacKenzie, Maryam Oskoui
Poster
Background: Hereditary spastic paraplegia (HSP) is a group of genetic diseases that cause progressive degeneration of the corticospinal tract. Historically, this disease was divided into two types:the classic subtype, with leg weakness and hypertonic bladder, and the complicated subtype, with features such as cerebellar ataxia or optic atrophy.Muta...
Article
Background: Serological testing is routinely performed in the work up for a diagnosis of Amyotrophic Lateral Sclerosis (ALS) to exclude pathologies with similar clinical phenotypes. Objective: To determine the proportion of serological workup that changes the primary diagnosis and/or clinical management for patients presenting with signs of ALS....
Article
Full-text available
Background: Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry...
Article
Introduction Patient registries serve an important role in rare disease research, particularly for the recruitment and planning of clinical trials. The Canadian Neuromuscular Disease Registry was established with the primary objective of improving the future for neuromuscular (NM) patients through the enablement and support of research into potenti...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinica...
Article
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Background: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. Objective: To determine the effects of...
Article
Full-text available
Objective Involvement of the neuromuscular junction (NMJ) in amyotrophic lateral sclerosis (ALS) has been reported and is increasingly recognized as an important pathophysiological aspect. The relationship between decrement and clinical measures for possible application as a biomarker has not been comprehensively explored. Methods We performed rou...
Article
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, characterized by fatigable weakness of the extraocular, bulbar, and limb musculature; prevalence is estimated at 14 to 32 per 100,000 in North America. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, resulting from clonal expansion of B-...
Article
Objective: To survey amyotrophic lateral sclerosis (ALS) health care providers to determine attitudes regarding physician-assisted death (PAD) after the Supreme Court of Canada (SCC) invalidated the Criminal Code provisions that prohibit PAD in February 2015. Methods: We conducted a Canada-wide survey of physicians and allied health professional...
Article
Full-text available
Pompe disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory weakness with or without cardiomyopathy. The objective of our review was to systematically evaluate the quality of evidence from the literature to formulate evidence-based guidelines for the diagno...
Article
Background: The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance. Methods: We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other mu...
Chapter
Clinical neurology trainees undergo a lengthy and complex process requiring integration of many fundamental skills that coalesce into sound diagnosis and decision making. This chapter discusses the development of an evidence-based neurology (EBN) curriculum in health education. Teaching and acquisition of critical appraisal skills is the primary ob...
Article
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Analysing the type and frequency of patient specific mutations that give rise to Duchenne Muscular Dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning and improved clinical care. Locus specific databases (LSDBs) allow for the collection, organization, storage and analysis of genetic variants of disease....
Article
Double-blinded randomized controlled trials (RCTs) have contributed much important evidence to guide treatment decisions in neurology. RCTs are relatively straightforward to conduct, provided that they investigate common diseases, have clearly defined outcome measures, and are of short duration. In neurology, however, many diseases are uncommon, ha...
Article
Full-text available
Patient registries represent an important platform across geographical areas that can provide critical epidemiological data and information on the effectiveness of therapies or devices within a given disease group. Neurological patient registries represent an exciting opportunity to directly impact patient care and clinical trial readiness. Neurolo...
Article
Split-night polysomnography is performed at our centre in all patients with ALS who require assessment for nocturnal hypoventilation and their response to non-invasive ventilation. The purpose of this study was to determine how successful this practice has been, reflected by whether a complete assessment was achieved by a single split-night polysom...
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Background Persons with certain neurological conditions have higher mortality rates than the population without neurological conditions, but the risk factors for increased mortality within diagnostic groups are less well understood. The interRAI CHESS scale has been shown to be a strong predictor of mortality in the overall population of persons re...