- Email: [email protected]
Management of myasthenia gravis
e476
Abstracts / Journal of the Neurological Sciences 357 (2015) e457–e512
the genetic cause for all patients with muscle diseases. The use of next generation sequencing technologies (NGS), namely exome and genome sequencing, has turned out to be an enormously powerful tool to identify causative mutations in single families, cohorts of well characterized independent patients, or even single sporadic cases. In addition to the identification of disease genes, NGS will also contribute to an improved understanding of disease pathomechanismsm, disease modifiers and the development of biomarkers. These additional benefits of NGS will rely on strong bioinformatics expertise, data sharing policies and willingness for networking. Results from two such networking projects applying NGS, Neuromics and MYO-SEQ, will be presented. The projects are already showing that the identification of novel muscle genes can facilitate personalized medicine, improve standards of care and accelerate the development of target–driven therapies. doi:10.1016/j.jns.2015.09.213
1640 WFN15-1883 Neuromuscular Disorders MT 7.4 Management of myasthenia gravis I. Illa. Neurology, Hospital Sant Pau. Universitat Autònoma Barcelona, Barcelona, Spain Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness and fatigability. The key to management is to understand that MG is a heterogeneous disease with several pathogenic subgroups. Clinically, patients may present with an ocular or generalized form of the disorder. Weakness varies from mild, to severe, and can be life-threatening. MG affects patients of all ages but the incidence is highest in those over 70–80 years. Thymic involvement is also variable, ranging from normal to hyperplasia or thymoma. Immunologically, 80% of patients have antibodies to acetylcholine receptor (AChR) and 10-15% have antibodies to musclespecific kinase (MuSK). Antibodies to LDL receptor-related protein 4 (LRP4)], low-affinity anti-AChR antibodies or cortactin have also been described. Accordingly, treatment varies, from AChE inhibitors for symptomatic therapy to thymectomy and, mainly, immunotherapy. Most patients respond to steroids or other immunosuppressants, but some are refractory to standard therapy. Current immunotherapies undoubtedly provide benefit and have greatly improved the quality of life of MG patients but are associated with side-effects. Increasing knowledge about the immunopathogenesis of MG is providing a rationale for treatment with new agents. In this session I will provide an update on the management of MG according to a recently designed guideline. doi:10.1016/j.jns.2015.09.214
1641 WFN15-1830 Neuromuscular Disorders MT 7.4 Statins and myopathies D. Hilton-Jones. Neurology, John Radcliffe Hospital, Oxford, United Kingdom Statins are now one of the most widely prescribed group of drugs worldwide, and in some countries can be bought without prescription, or medical advice, "over the counter". They have come into widespread use because they are so effective in lowering serum cholesterol, which in turn is associated with a substantial reduction in cardiovascular and cerebrovascular morbidity and mortality. They
act by inhibiting 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR), a rate limiting enzyme in the synthesis of cholesterol. Thousands of papers have been published describing issues concerning skeletal muscle, but despite the many millions of patients studied, in often enormous clinical trials, mostly cardiologically-led, considerable confusion and uncertainty remains as to associated muscle syndromes precipitated by them, and the question of whether or not they are safe to be given to patients with an established myopathy. This presentation will review the available data and discuss clinical features. In brief summary, there are four main skeletal muscle "syndromes" associated with statin use: 1) Asymptomatic elevation of serum creatine kinase (CK) (probably common) 2) Myalgia, often associated with a raised CK (common) 3) Rhabdomyolysis (rare but potentially fatal) 4) An immune-mediated necrotising myopathy that persists despite statin withdrawal, and responds to immunosuppressant drug treatment (probably very rare). It may be associated with antibodies against HMGCR In the majority of patients with a pre-existing myopathy, statins are probably safe, but certain precautions are required. Statins are often wrongly blamed, by patients and physicians, for neuromuscular symptoms, potentially depriving patients of an effective therapy. doi:10.1016/j.jns.2015.09.215
1642 WFN15-1853 Movement Disorders MT 2.1 - Movement Disorders revisited Parkinsonism and Parkinson’s disease K. Kompoliti. Neurological Sciences, Rush University Medical Center, Chicago, USA Parkinsonism is a clinical syndrome characterized by bradykinesia and at least one of: rest tremor, muscular rigidity and postural reflex abnormalities. Bradykinesia is the defining feature of parkinsonism and is characterized by decrement (fatigability) and breaking down of the movement. Parkinson’s disease is the most common neurodegenerative cause of parkinsonism, accounting for approximately 80% of cases of parkinsonism. Other neurodegenerative conditions presenting with parkinsonism include Multiple System Atrophy, Progressive Supranuclear Palsy and Corticobasal Degeneration. These conditions tend not to respond as well to dopaminergic treatments and have a worse prognosis compared to typical Parkinson’s disease. Parkinsonism can also be symptomatic, resulting from drugs, toxins, infections, vascular disease and rarely structural lesions. Parkinsonism remains a clinical diagnosis and laboratory and imaging tools are mostly ancillary to making the diagnosis. doi:10.1016/j.jns.2015.09.216
1643 WFN15-1850 Movement Disorders MT 2.1 - Movement Disorders revisited Dystonia F. Cardoso. Internal Medicine, Neurology Service, Belo Horizonte, Brazil Dystonia Revisited Francisco Cardoso MD PhD FAAN Neurology Service, Internal Medicine Department, UFMG, Belo Horizonte, MG, Brazil
Abstracts / Journal of the Neurological Sciences 357 (2015) e457–e512
the genetic cause for all patients with muscle diseases. The use of next generation sequencing technologies (NGS), namely exome and genome sequencing, has turned out to be an enormously powerful tool to identify causative mutations in single families, cohorts of well characterized independent patients, or even single sporadic cases. In addition to the identification of disease genes, NGS will also contribute to an improved understanding of disease pathomechanismsm, disease modifiers and the development of biomarkers. These additional benefits of NGS will rely on strong bioinformatics expertise, data sharing policies and willingness for networking. Results from two such networking projects applying NGS, Neuromics and MYO-SEQ, will be presented. The projects are already showing that the identification of novel muscle genes can facilitate personalized medicine, improve standards of care and accelerate the development of target–driven therapies. doi:10.1016/j.jns.2015.09.213
1640 WFN15-1883 Neuromuscular Disorders MT 7.4 Management of myasthenia gravis I. Illa. Neurology, Hospital Sant Pau. Universitat Autònoma Barcelona, Barcelona, Spain Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness and fatigability. The key to management is to understand that MG is a heterogeneous disease with several pathogenic subgroups. Clinically, patients may present with an ocular or generalized form of the disorder. Weakness varies from mild, to severe, and can be life-threatening. MG affects patients of all ages but the incidence is highest in those over 70–80 years. Thymic involvement is also variable, ranging from normal to hyperplasia or thymoma. Immunologically, 80% of patients have antibodies to acetylcholine receptor (AChR) and 10-15% have antibodies to musclespecific kinase (MuSK). Antibodies to LDL receptor-related protein 4 (LRP4)], low-affinity anti-AChR antibodies or cortactin have also been described. Accordingly, treatment varies, from AChE inhibitors for symptomatic therapy to thymectomy and, mainly, immunotherapy. Most patients respond to steroids or other immunosuppressants, but some are refractory to standard therapy. Current immunotherapies undoubtedly provide benefit and have greatly improved the quality of life of MG patients but are associated with side-effects. Increasing knowledge about the immunopathogenesis of MG is providing a rationale for treatment with new agents. In this session I will provide an update on the management of MG according to a recently designed guideline. doi:10.1016/j.jns.2015.09.214
1641 WFN15-1830 Neuromuscular Disorders MT 7.4 Statins and myopathies D. Hilton-Jones. Neurology, John Radcliffe Hospital, Oxford, United Kingdom Statins are now one of the most widely prescribed group of drugs worldwide, and in some countries can be bought without prescription, or medical advice, "over the counter". They have come into widespread use because they are so effective in lowering serum cholesterol, which in turn is associated with a substantial reduction in cardiovascular and cerebrovascular morbidity and mortality. They
act by inhibiting 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR), a rate limiting enzyme in the synthesis of cholesterol. Thousands of papers have been published describing issues concerning skeletal muscle, but despite the many millions of patients studied, in often enormous clinical trials, mostly cardiologically-led, considerable confusion and uncertainty remains as to associated muscle syndromes precipitated by them, and the question of whether or not they are safe to be given to patients with an established myopathy. This presentation will review the available data and discuss clinical features. In brief summary, there are four main skeletal muscle "syndromes" associated with statin use: 1) Asymptomatic elevation of serum creatine kinase (CK) (probably common) 2) Myalgia, often associated with a raised CK (common) 3) Rhabdomyolysis (rare but potentially fatal) 4) An immune-mediated necrotising myopathy that persists despite statin withdrawal, and responds to immunosuppressant drug treatment (probably very rare). It may be associated with antibodies against HMGCR In the majority of patients with a pre-existing myopathy, statins are probably safe, but certain precautions are required. Statins are often wrongly blamed, by patients and physicians, for neuromuscular symptoms, potentially depriving patients of an effective therapy. doi:10.1016/j.jns.2015.09.215
1642 WFN15-1853 Movement Disorders MT 2.1 - Movement Disorders revisited Parkinsonism and Parkinson’s disease K. Kompoliti. Neurological Sciences, Rush University Medical Center, Chicago, USA Parkinsonism is a clinical syndrome characterized by bradykinesia and at least one of: rest tremor, muscular rigidity and postural reflex abnormalities. Bradykinesia is the defining feature of parkinsonism and is characterized by decrement (fatigability) and breaking down of the movement. Parkinson’s disease is the most common neurodegenerative cause of parkinsonism, accounting for approximately 80% of cases of parkinsonism. Other neurodegenerative conditions presenting with parkinsonism include Multiple System Atrophy, Progressive Supranuclear Palsy and Corticobasal Degeneration. These conditions tend not to respond as well to dopaminergic treatments and have a worse prognosis compared to typical Parkinson’s disease. Parkinsonism can also be symptomatic, resulting from drugs, toxins, infections, vascular disease and rarely structural lesions. Parkinsonism remains a clinical diagnosis and laboratory and imaging tools are mostly ancillary to making the diagnosis. doi:10.1016/j.jns.2015.09.216
1643 WFN15-1850 Movement Disorders MT 2.1 - Movement Disorders revisited Dystonia F. Cardoso. Internal Medicine, Neurology Service, Belo Horizonte, Brazil Dystonia Revisited Francisco Cardoso MD PhD FAAN Neurology Service, Internal Medicine Department, UFMG, Belo Horizonte, MG, Brazil