E-Book, Englisch, Band Volume 32-3, 305 Seiten
Reihe: The Clinics: Radiology
E-Book, Englisch, Band Volume 32-3, 305 Seiten
Reihe: The Clinics: Radiology
ISBN: 978-0-323-32038-2
Verlag: Elsevier Health Care - Major Reference Works
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Myopathies
;2
3;Copyright
;3
4;Contributors;4
5;Contents;8
6;Neurologic Clinics
;12
7;Preface
;14
8;A Pattern Recognition Approach to Patients with a Suspected Myopathy;16
8.1;Key points;16
8.2;Introduction;16
8.3;Clinical evaluation;17
8.3.1;Which Negative and/or Positive Symptoms Do Patients Demonstrate?;17
8.3.2;What is the Temporal Evolution?;20
8.3.3;Is There a Family History of a Myopathic Disorder?;22
8.3.4;Are There Precipitating Factors That Trigger Episodic Weakness or Stiffness?;22
8.3.5;Are There Associated Systemic Symptoms or Signs?;23
8.3.6;What is the Distribution of Weakness?;25
8.4;Pattern recognition approach to myopathic disorders;27
8.4.1;Pattern 1: Proximal Limb-Girdle Weakness;27
8.4.2;Pattern 2: Distal Weakness;27
8.4.3;Pattern 3: Proximal Arm/Distal Leg Weakness (Scapuloperoneal);27
8.4.4;Pattern 4: Distal Arm/Proximal Leg Weakness;28
8.4.4.1;68-year old with slowly progressive muscle weakness;28
8.4.4.2;Comment;28
8.4.5;Pattern 5: Ptosis with or Without Ophthalmoparesis;29
8.4.5.1;70-year old with progressive dysphagia and weakness;29
8.4.5.2;Comment;30
8.4.6;Pattern 6: Prominent Neck Extensor Weakness;30
8.4.7;Pattern 7: Bulbar Weakness;30
8.4.8;Pattern 8: Episodic Pain, Weakness, and Myoglobinuria;31
8.4.9;Pattern 9: Episodic Weakness Delayed or Unrelated to Exercise;31
8.4.10;Pattern 10: Stiffness and Decreased Ability to Relax;31
8.5;Laboratory approach in the evaluation of a suspected myopathy;32
8.5.1;CK;32
8.5.2;Electrophysiologic Studies;36
8.5.3;The Muscle Biopsy;36
8.5.4;Molecular Genetic Studies;38
8.5.5;Other Tests;38
8.6;Summary;39
8.7;Web sites;40
8.8;References;40
9;Idiopathic Inflammatory Myopathies;42
9.1;Key points;42
9.2;Epidemiology;42
9.3;Clinical presentation;45
9.3.1;Dermatomyositis;45
9.3.2;Polymyositis;46
9.3.3;Necrotizing Myopathy;46
9.4;Conditions associated with dermatomyositis, polymyositis, and necrotizing myopathy;50
9.4.1;Polyarthritis;50
9.4.2;Interstitial Lung Disease;50
9.4.3;Malignancy;50
9.4.4;Autoimmune Necrotizing Myopathy;51
9.4.5;Cardiac Defects;51
9.5;Laboratory studies in dermatomyositis, polymyositis, and necrotizing myopathy;51
9.5.1;Cancer Screening;51
9.5.2;Pulmonary Function Testing;52
9.5.3;Biomarker Monitoring;52
9.5.4;Antibody Identification;53
9.6;Electrophysiology of dermatomyositis, polymyositis, and necrotizing myopathy;54
9.7;Muscle imaging;54
9.8;Muscle histopathology and pathogenesis of DM, PM, and NM;55
9.8.1;Dermatomyositis;55
9.8.2;Polymyositis;57
9.8.3;Necrotizing Myopathy;58
9.9;Therapy for dermatomyositis, polymyositis, and necrotizing myopathy;59
9.9.1;Corticosteroids;59
9.9.2;Methotrexate;60
9.9.3;Azathioprine;63
9.9.4;Intravenous Immunoglobulin;64
9.9.5;Treatment of Refractory Patients;64
9.9.6;IIM Associated with ILD;65
9.9.7;Promising Therapies;66
9.9.8;Physical Therapy;66
9.10;Prognosis;67
9.11;References;67
10;Inclusion Body Myositis;76
10.1;Key points;76
10.2;Epidemiology;76
10.2.1;Clinical Presentation;77
10.2.2;Associated Conditions;78
10.2.3;Laboratory and Electrophysiologic Testing;79
10.2.4;Muscle Imaging;79
10.2.5;Muscle Histopathology;80
10.2.6;Pathogenesis;81
10.3;Diagnostic and research criteria;83
10.3.1;ENMC 2000;84
10.3.2;MRC 2010;84
10.3.3;ENMC 2011;84
10.3.4;Therapy;85
10.3.5;Ongoing Research;86
10.3.6;Prognosis;86
10.3.7;Exercise;89
10.4;Summary;89
10.5;References;89
11;Toxic Myopathies;94
11.1;Key points;94
11.2;Introduction;94
11.3;Pathophysiology/Pathogenesis;95
11.4;Necrotizing myopathy;95
11.4.1;Introduction;95
11.4.2;Statins;95
11.4.2.1;Clinical presentation;95
11.4.2.2;Laboratory features and electrophysiology;97
11.4.2.3;Histopathology;97
11.4.2.4;Pathogenesis;97
11.4.2.5;Treatment;97
11.4.3;Cholesterol-Lowering Drugs (Excluding Statins);97
11.4.4;Immunophilins;97
11.4.4.1;Clinical features;98
11.4.4.2;Laboratory features and electrophysiology;98
11.4.4.3;Histopathology;98
11.4.4.4;Pathogenesis;98
11.4.4.5;Treatment;98
11.4.5;Labetolol;98
11.4.5.1;Clinical features;98
11.4.5.2;Laboratory features and electrophysiology;98
11.4.5.3;Histopathology;98
11.4.5.4;Pathogenesis;98
11.4.6;Propofol;98
11.4.6.1;Clinical features;98
11.4.6.2;Laboratory features;99
11.4.6.3;Histopathology;99
11.4.6.4;Pathogenesis;99
11.4.6.5;Treatment;99
11.4.7;Snake Venom;99
11.4.7.1;Clinical features;99
11.4.7.2;Histopathology and pathogeneisis;99
11.4.7.3;Treatment;99
11.5;Amphiphillic drug myopathy (drug-induced autophagic lysosomal myopathy);99
11.5.1;Chloroquine;99
11.5.1.1;Clinical features;99
11.5.1.2;Laboratory features and neurophysiology;100
11.5.1.3;Histopathology;100
11.5.1.4;Pathogenesis;100
11.5.1.5;Hydroxychloroquine;100
11.5.2;Amiodarone;100
11.5.2.1;Clinical features;100
11.5.2.2;Laboratory features;100
11.5.2.3;Histopathology;101
11.5.2.4;Pathogenesis;101
11.5.2.5;Treatment;101
11.6;Antimicrotubular drug myopathies;101
11.6.1;Colchicine;101
11.6.1.1;Clinical features;101
11.6.1.2;Laboratory features;101
11.6.1.3;Electrophysiologic findings;101
11.6.1.4;Histopathology;101
11.6.1.5;Pathogenesis;102
11.6.1.6;Treatment;102
11.6.2;Vincristine;102
11.6.2.1;Clinical features;102
11.6.2.2;Laboratory features;102
11.6.2.3;Histopathology;102
11.6.2.4;Pathogenesis;102
11.7;Drug-induced mitochondrial myopathies;102
11.7.1;Zidovudine (Azidothymidine);102
11.7.1.1;Clinical features;102
11.7.1.2;Laboratory features;103
11.7.1.3;Histopathology;103
11.7.1.4;Pathogenesis;103
11.7.1.5;Treatment;103
11.7.2;Other Antiviral Agents;104
11.8;Drug-induced inflammatory myopathies;104
11.8.1;Cholesterol-Lowering Agents;104
11.8.2;l-tryptophan/Eosinophilia Myalgia Syndrome;104
11.8.2.1;Clinical features;104
11.8.2.2;Laboratory features;104
11.8.2.3;Histopathology;104
11.8.2.4;Pathogenesis;104
11.8.2.5;Treatment;105
11.8.2.6;Toxic oil syndrome;105
11.8.3;d-Penicillamine;105
11.8.4;Cimetidine;105
11.8.5;Procainamide;105
11.8.6;Phenytoin;105
11.8.7;Lamotrigine;106
11.8.8;Interferon Alfa;106
11.8.9;Imatinib Mesylate (Gleevic);106
11.9;Myopathies due to impaired protein synthesis or increased catabolism;106
11.9.1;Steroid Myopathy;106
11.9.1.1;Clinical features;106
11.9.1.2;Laboratory and electrophysiologic features;106
11.9.1.3;Histopathology;107
11.9.1.4;Pathogenesis;107
11.9.1.5;Treatment;107
11.9.2;Finasteride;107
11.9.2.1;Clincal features;107
11.9.2.2;Laboratory features;107
11.9.2.3;Electrophysiologic findings;107
11.9.2.4;Histopathology;107
11.9.2.5;Pathogenesis;107
11.9.2.6;Treatment;108
11.9.3;Emetine;108
11.9.3.1;Clinical features;108
11.9.3.2;Laboratory features;108
11.9.3.3;Histopathology;108
11.9.3.4;Pathogenesis;108
11.9.3.5;Treatment;108
11.10;Toxic myopathies with unknown pathogenic mechanism;108
11.10.1;Acute Quadriplegic Myopathy/Critical Illness Myopathy;108
11.10.1.1;Clinical features;108
11.10.1.2;Laboratory features and electrophysiologic findings;109
11.10.1.3;Histopathology;109
11.10.1.4;Pathogenesis;109
11.10.1.5;Treatment;109
11.10.2;Omeprazole;109
11.10.3;Isoretinion;109
11.11;Myopathies associated with anesthetic agents and centrally acting medications;109
11.11.1;Malignant Hyperthermia;109
11.11.1.1;Clinical features;109
11.11.1.2;Laboratory features and electrophysiologic studies;110
11.11.1.3;Histopathology;110
11.11.1.4;Pathogenesis and molecular genetics;110
11.11.1.5;Treatment;110
11.12;Myopathies secondary to drugs of abuse;110
11.12.1;Alcoholic Myopathy;110
11.12.2;Other Drugs;111
11.13;Summary;111
11.14;References;111
12;Duchenne and Becker Muscular Dystrophies;118
12.1;Key points;118
12.2;Introduction;118
12.3;Clinical findings;119
12.3.1;Duchenne Muscular Dystrophy;119
12.3.2;Becker Muscular Dystrophy;119
12.3.3;Rating Scales;120
12.4;Diagnosis;120
12.4.1;Serum Chemistries;120
12.4.2;Muscle Biopsy;121
12.4.3;Histopathology;121
12.4.4;Assessment of Dystrophin Expression;121
12.4.5;Mutational Analysis;122
12.5;Imaging;123
12.6;Diagnostic dilemmas;123
12.6.1;Exceptions to the Reading Frame Rule;123
12.7;Genetic modifiers;123
12.8;Management;124
12.8.1;Management Goals in DMD;124
12.9;Pharmacologic therapy;124
12.9.1;Corticosteroids;124
12.9.2;Cardiac Care;125
12.10;Nonpharmacologic therapies;125
12.10.1;Pulmonary Care;125
12.10.2;Scoliosis;126
12.11;Novel therapies;126
12.11.1;Nonsense Suppression;126
12.11.2;Exon Skipping;126
12.11.3;Gene Transfer;127
12.12;Summary;127
12.13;References;127
13;Congenital Myopathies and Muscular Dystrophies;136
13.1;Key points;136
13.2;Introduction;136
13.3;Case 1;137
13.4;Case 2;139
13.5;Case 3;142
13.6;Case 4;145
13.7;Case 5;146
13.8;Summary;149
13.9;References;149
14;Myotonic Dystrophy;152
14.1;Key points;152
14.2;Epidemiology;152
14.3;Genetics;153
14.4;Clinical presentation of Myotonic Dystrophy;154
14.5;Congenital DM1;154
14.6;Childhood DM1;155
14.7;Classical DM1;155
14.8;Minimal DM1;155
14.9;Neuromuscular features of DM2;155
14.10;Systemic features;156
14.10.1;Cardiac Disease;156
14.10.2;Ocular;156
14.10.3;CNS;156
14.10.4;Other Systemic Features;157
14.11;Laboratory and electrophysiologic testing;157
14.11.1;Genetic Testing;157
14.11.2;Electrophysiology;157
14.11.3;Muscle Pathology;158
14.12;Pathogenesis;158
14.12.1;RNA Toxicity;158
14.12.2;Sequestration of MBNL Proteins;158
14.12.3;Signaling Changes and Aberrant Translation of Expanded Repeats;159
14.12.4;Other Effects;159
14.12.5;Pathophysiology of Congenital DM1;159
14.12.6;Therapy and Management for DM1 and DM2;159
14.12.7;Experimental Treatments for DM1 and DM2;160
14.13;References;160
15;Facioscapulohumeral Muscular Dystrophy;168
15.1;Key points;168
15.2;Introduction;168
15.3;Clinical findings;169
15.4;Diagnosis;170
15.5;Pathophysiology;171
15.6;Therapeutic strategies;172
15.7;Summary and future directions;173
15.8;References;173
16;The Limb-Girdle Muscular Dystrophies;176
16.1;Key points;176
16.2;Introduction;176
16.3;LGMD2A—calpain;177
16.3.1;Clinical;177
16.3.2;Laboratory;180
16.3.3;Diagnosis;181
16.3.4;Treatment;181
16.4;LGMD2B—dysferlin;181
16.4.1;Clinical;181
16.4.2;Laboratory;182
16.4.3;Diagnosis;182
16.4.4;Treatment;182
16.5;LGMD2C–F—a-, ß-, .-, and d-sarcoglycans;183
16.5.1;Clinical;183
16.5.2;Laboratory;184
16.5.3;Diagnosis;184
16.5.4;Treatment;185
16.6;LGMD2I—fukutin-related protein;185
16.6.1;Clinical;185
16.6.2;Laboratory;185
16.6.3;Diagnosis;186
16.6.4;Treatment;186
16.7;LGMD2L—anoctamin 5;186
16.7.1;Clinical;186
16.7.2;Laboratory;187
16.7.3;Diagnosis;188
16.7.4;Treatment;188
16.8;LGMD1B—lamin A/C;188
16.8.1;Clinical;189
16.8.2;Laboratory;189
16.8.3;Diagnosis;189
16.8.4;Treatment;189
16.9;Summary;190
16.10;References;191
17;Pompe Disease;198
17.1;Key points;198
17.2;Introduction;199
17.2.1;Genetic Etiology and Prevalence;200
17.3;Clinical presentation;203
17.4;Pathogenesis of Pompe disease;204
17.5;Newborn screening for Pompe disease;205
17.6;The University of Kansas Medical Center case series;205
17.7;Discussion, current management, and therapeutic options;212
17.8;Summary and future directions;216
17.9;Acknowledgments;216
17.10;References;216
18;Metabolic and Mitochondrial Myopathies;224
18.1;Key points;224
18.2;Introduction;224
18.3;Case report;225
18.4;Carbohydrate disorders causing exercise-induced symptoms;225
18.4.1;Muscle Phosphorylase Deficiency (McArdle Disease, Glycogen Storage Disease Type V);225
18.4.1.1;Pathophysiology;225
18.4.1.2;Clinical features;225
18.4.1.3;Diagnosis;226
18.4.1.4;Management;227
18.4.2;Phosphorylase b Kinase Deficiency (Glycogen Storage Disease Type IX);227
18.4.2.1;Pathophysiology;227
18.4.2.2;Clinical features;227
18.4.2.3;Diagnosis;228
18.4.2.4;Management;228
18.4.3;Muscle PFK Deficiency (Tauri Disease, Glycogen Storage Disease Type VII);228
18.4.3.1;Pathophysiology;228
18.4.3.2;Clinical features;228
18.4.3.3;Diagnosis;228
18.4.3.4;Management;228
18.4.4;Phosphoglucomutase Deficiency;229
18.4.4.1;Pathophysiology;229
18.4.4.2;Clinical features;229
18.4.4.3;Management;229
18.4.5;Distal Glycolytic Defects;229
18.4.5.1;Pathophysiology;229
18.4.5.2;Clinical features;229
18.4.5.3;Diagnosis;230
18.4.5.4;Management;230
18.4.6;Other Rare Defects;230
18.5;Carbohydrate disorders causing muscle weakness;231
18.5.1;Debrancher Deficiency (Cori Disease, Glycogen Storage Disease Type III);231
18.5.1.1;Pathophysiology;231
18.5.1.2;Clinical features;231
18.5.1.3;Diagnosis;231
18.5.1.4;Management;232
18.5.2;Glycogen Branching Enzyme Deficiency (Andersen Disease, GSD Type IV);232
18.5.2.1;Pathophysiology;232
18.5.2.2;Clinical features;232
18.5.2.3;Diagnosis;232
18.5.2.4;Management;232
18.6;Lipid metabolism disorders causing muscle weakness and lipid accumulation;232
18.6.1;Primary Carnitine Deficiency;232
18.6.1.1;Pathophysiology;232
18.6.1.2;Clinical features;233
18.6.1.3;Diagnosis;234
18.6.1.4;Management;234
18.6.2;Neutral Lipid Storage Disease;234
18.6.2.1;Pathophysiology;234
18.6.2.2;Clinical features;234
18.6.2.3;Diagnosis;234
18.6.2.4;Management;234
18.6.3;MADD;234
18.6.3.1;Pathophysiology;234
18.6.3.2;Clinical features;234
18.6.3.3;Diagnosis;235
18.6.3.4;Management;235
18.7;Lipid metabolism disorders causing recurrent myalgia, rhabdomyolysis, and myoglobinuria;235
18.7.1;CPT2 Deficiency;235
18.7.1.1;Pathophysiology;235
18.7.1.2;Clinical features;235
18.7.1.3;Diagnosis;235
18.7.1.4;Management;236
18.7.2;VLCAD Deficiency;236
18.7.2.1;Pathophysiology;236
18.7.2.2;Clinical features;236
18.7.2.3;Diagnosis;236
18.7.2.4;Management;236
18.7.3;TP/Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency;236
18.7.3.1;Pathophysiology;236
18.7.3.2;Clinical features;236
18.7.3.3;Diagnosis;236
18.7.3.4;Management;237
18.7.4;Lipin-1 Deficiency;237
18.7.4.1;Pathophysiology;237
18.7.4.2;Clinical features;237
18.7.4.3;Diagnosis;237
18.7.4.4;Management;237
18.7.5;Mitochondrial Myopathies;237
18.7.6;mtDNA Mutations;237
18.7.6.1;Pathophysiology;237
18.7.6.2;Clinical;237
18.7.6.3;Diagnosis;239
18.7.7;Mitochondrial Myopathy due to Nuclear Mutations Causing Multiple mtDNA Deletions or mtDNA Depletion;239
18.7.7.1;Pathogenesis;239
18.7.7.2;Diagnosis;239
18.7.8;Mitochondrial Myopathy due to Nuclear DNA Mutations Affecting Individual Subunits, Prosthetic Groups, or Respiratory Comple ...;239
18.7.8.1;Pathophysiology/Clinical;239
18.7.9;Mitochondrial Myopathy due to Defects in Mitochondrial tRNA Translation;240
18.7.9.1;Pathophysiology/Clinical;240
18.7.9.2;Diagnosis;240
18.7.9.3;Management;241
18.8;References;241
19;Muscle Channelopathies;248
19.1;Key points;248
19.2;Introduction;248
19.3;NDM;248
19.3.1;Clinical Features;249
19.3.1.1;MC;249
19.3.1.2;PMC;249
19.3.1.3;Sodium channel myotonias;249
19.3.2;Diagnosis;250
19.3.3;Pathophysiology;250
19.3.4;Therapeutic Options in NDM;251
19.4;Congenital myasthenic syndromes;252
19.4.1;Slow-channel CMS;253
19.4.2;Fast-channel CMS;253
19.5;Periodic paralyses;253
19.5.1;Clinical Features;253
19.5.1.1;Hyperkalemic periodic paralysis;253
19.5.1.2;Hypokalemic periodic paralysis;254
19.5.1.3;ATS;254
19.5.2;Diagnosis;254
19.5.3;Pathophysiology;256
19.5.4;Therapeutic Options;256
19.6;Summary;258
19.7;References;258
20;Distal Myopathies;264
20.1;Key points;264
20.2;Approach;264
20.3;Classic distal myopathies;266
20.3.1;Welander Distal Myopathy: Late Adult Onset, Type 1;266
20.3.2;Tibial Muscular Dystrophy: Late Onset Distal Myopathy Type 2;268
20.3.3;Udd Late Onset Distal Myopathy Type 2a;269
20.3.4;Markesbery-Griggs Late Onset Distal Myopathy Type 2b;270
20.3.5;Nonaka Distal Myopathy: Early Adult Onset, Type 1, Distal Myopathy with Rimmed Vacuoles;270
20.3.6;Miyoshi Distal Myopathy: Early Adult Onset, Type 2;272
20.3.7;Laing Distal Myopathy: Early Onset, Type 3;274
20.4;Myofibrillar Myopathy;275
20.4.1;Clinical Manifestations;275
20.4.2;Clinical Manifestations with Mutations;276
20.4.3;Pathologic Alterations;276
20.4.4;Weakness Onset Variability;277
20.5;Distal myopathies not yet classified;277
20.5.1;AD Inheritance Late Onset Distal Myopathy;277
20.5.2;AD Weakness of Extremities;278
20.5.3;AD Adult Onset Vacuolar Distal Myopathy;278
20.5.4;AD Adult Onset Slow Progression;279
20.5.5;AD Late Onset;279
20.6;Other myopathies with distal weakness;279
20.6.1;Childhood Onset Distal Myopathy;280
20.6.2;Other Muscular Dystrophies;281
20.6.3;Inflammatory Myopathies;281
20.6.4;Metabolic and Congenital Myopathies;282
20.6.5;Myasthenia Gravis;282
20.7;References;282
20.8;Index
;290
A Pattern Recognition Approach to Patients with a Suspected Myopathy
Richard J. Barohn, MDa*rbarohn@kumc.edu, Mazen M. Dimachkie, MDb and Carlayne E. Jackson, MDc, aDepartment of Neurology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 2012, Kansas City, KS 66160, USA; bNeuromuscular Section, Neurophysiology Division, Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 2012, Kansas City, KS 66160, USA; cDivision of Neurology, UT Medicine San Antonio, University of Texas Health Science Center, 8300 Floyd Curl Drive, Mail Code 7883, San Antonio, TX 78229-3900, USA *Corresponding author. Myopathies are a heterogeneous group of disorders that can be challenging to diagnose. This review provides a diagnostic approach based predominantly on the clinical history and neurologic examination. Laboratory testing that can be used to confirm the suspected diagnosis based on this pattern recognition approach is also discussed. Careful consideration of the distribution of muscle weakness and attention to common patterns of involvement in the context of other aspects of the neurologic examination and laboratory evaluation should assist the clinician in making a timely and accurate diagnosis and can sometimes minimize the expense of further testing. Keywords Myopathy Limb-girdle Distal myopathy Inflammatory myopathy Metabolic myopathy Myotonia Key points
• The initial key to the diagnosis of myopathies is recognition of a clinical pattern. • There are 6 key questions the clinician should consider in arriving at the pattern that fits the patient. • After arriving at the pattern that fits best, then the clinician can better determine the most appropriate diagnostic tests and management. Introduction
Myopathies are disorders affecting the channel, structure, or metabolism of skeletal muscle. Myopathies can be distinguished from other disorders of the motor unit, including the neuromuscular junction, peripheral nerve, or motor neuron, by characteristic clinical and laboratory features. Therefore, the first goal in approaching patients with a suspected muscle disease is to determine the correct site of the lesion. Once the lesion is localized to the muscle, the next step is to identify whether the myopathy is caused by a defect in the muscle channel, muscle structure, or a dysfunction in muscle metabolism. The second goal is to determine the cause of the myopathy. In general, myopathies can be classified into acquired or hereditary disorders (Box 1). Finally, the third goal in the authors’ approach is to determine if there is a specific treatment and, if not, to optimally manage the patients’ symptoms in order to maximize their functional abilities and enhance their quality of life. Box 1 Classification of myopathies Acquired Drug-induced myopathies Endocrine myopathies Inflammatory/immune myopathies Myopathies associated with other systemic illness Toxic myopathies Hereditary Channelopathies Congenital myopathies Metabolic myopathies Mitochondrial myopathies Muscular dystrophies Myotonias Clinical evaluation
The most important component of evaluating patients with a suspected myopathy is obtaining a comprehensive medical history. The history should allow the clinician to make a reasonable preliminary diagnosis that places patients into one of the categories in Box 1. The findings on the physical examination, in particular the distribution of muscle weakness, should provide additional information in determining the correct diagnosis. The results of laboratory studies (blood tests, electrodiagnostic studies, muscle biopsy, molecular genetic studies) then play a confirmatory diagnostic role.1–4 The first step in this clinical approach is to ask 6 key questions regarding the patients’ symptoms. 1. Which Negative and/or Positive Symptoms Do Patients Demonstrate? 2. What is the Temporal Evolution? 3. Is There a Family History of a Myopathic Disorder? 4. Are There Precipitating Factors That Trigger Episodic Weakness or Stiffness? 5. Are There Associated Systemic Symptoms or Signs? 6. What is the Distribution of Weakness? Which Negative and/or Positive Symptoms Do Patients Demonstrate?
Symptoms of muscle disease (Box 2) can be divided into negative complaints, such as exercise intolerance, fatigue, muscle atrophy and weakness, and positive complaints, such as contractures, cramps, myalgias, muscle stiffness, and myoglobinuria. Box 2 Symptoms associated with myopathies Negative Exercise intolerance Fatigue Muscle atrophy Weakness Positive Cramps Contractures Muscle hypertrophy Myalgias Myoglobinuria Stiffness Weakness is by far the most common negative symptom reported by patients with muscle disease. When the upper extremities are involved, patients notice trouble brushing their teeth, combing their hair, or lifting objects overhead. If the weakness involves the lower extremities, patients will complain of difficulty arising from a low chair or toilet, getting up from a squatted position, or climbing stairs. These symptoms in the arms and legs indicate proximal muscle weakness, which is probably the most common distribution of weakness in a myopathic disorder (see later discussion). Less commonly, patients with myopathies can complain of distal weakness manifested as difficulty turning a key in the ignition, opening jars, or gait instability caused by foot drop. Some myopathies may also result in cranial muscle weakness resulting in complaints of slurred speech, difficulty swallowing, or double vision. Fatigue is a much less useful negative symptom because it may be a result of patients’ overall health, cardiopulmonary status, level of conditioning, sleeping habits, or emotional state. Many patients who complain of generalized weakness or fatigue do not have a myopathy, particularly if the neurologic examination is normal. However, it is important to define the intensity and duration of exercise that provokes the fatigue because metabolic and mitochondrial myopathies can cause abnormal fatigability after exercise. Positive symptoms associated with myopathies may include cramps, contractures, myalgias, muscle stiffness, or myoglobinuria. Myalgia, like fatigue, is another nonspecific symptom of some myopathies (Box 3). Myalgias may be episodic such as in metabolic myopathies or nearly constant such as in inflammatory muscle diseases. However, muscle pain is usually not common in most muscle diseases; pain is more likely to be caused by orthopedic or rheumatologic disorders. It is extremely uncommon for a myopathy to be responsible for vague aches and muscle discomfort in the presence of a normal neuromuscular examination and laboratory studies. Box 3 Muscle diseases associated with myalgias Toxic/drug-induced myopathies (statins and others) Eosinophilia-myalgia syndrome Hypothyroid myopathy Inflammatory myopathies (dermatomyositis, polymyositis) Myotonic disorders Mitochondrial myopathies Tubular aggregate myopathy Muscular dystrophies, examples X-linked myalgia and cramps/Becker dystrophy variant Infectious myositis (especially viral) Myoadenylate deaminase deficiency (controversial) Muscle cramps are a specific type of muscle pain. They are typically benign, occurring frequently in normal individuals, and are seldom a feature of a primary myopathy. Cramps commonly occur because of dehydration, hyponatremia, azotemia, myxedema, and disorders of the nerve or motor neuron (especially amyotrophic lateral sclerosis) or most often are benign and not related to an underlying disease process. Cramps may last from seconds to minutes and are usually localized to a...
