Congential myopathies, Muscular dystropies, Glycogen storage diseases of muscle, and Idiopathic and Inflammatory myopathies are presented in this volume of Neurologic Clinics. Topics include: Muscle channelopathies; Pompe disease; Congenital myopathies and muscular dystrophies; Duchenne and Becker muscular dystrophies; Distal myopathies; Limb-girdle muscular dystrophy; Fascioscapulomuneral muscular dystrophy; Myotonic dystrophy; Metabolic and mitochondrial myopathies; Sporadic inclusion body myositis; Toxic myopathies; Idiopathic Inflammatory myopathies; Approach to muscle disease.
Front Cover 1
Myopathies
2
Copyright
3
Contributors 4
Contents 8
Neurologic Clinics
12
Preface
14
A Pattern Recognition Approach to Patients with a Suspected Myopathy 16
Key points 16
Introduction 16
Clinical evaluation 17
Which Negative and/or Positive Symptoms Do Patients Demonstrate? 17
What is the Temporal Evolution? 20
Is There a Family History of a Myopathic Disorder? 22
Are There Precipitating Factors That Trigger Episodic Weakness or Stiffness? 22
Are There Associated Systemic Symptoms or Signs? 23
What is the Distribution of Weakness? 25
Pattern recognition approach to myopathic disorders 27
Pattern 1: Proximal Limb-Girdle Weakness 27
Pattern 2: Distal Weakness 27
Pattern 3: Proximal Arm/Distal Leg Weakness (Scapuloperoneal) 27
Pattern 4: Distal Arm/Proximal Leg Weakness 28
68-year old with slowly progressive muscle weakness 28
Comment 28
Pattern 5: Ptosis with or Without Ophthalmoparesis 29
70-year old with progressive dysphagia and weakness 29
Comment 30
Pattern 6: Prominent Neck Extensor Weakness 30
Pattern 7: Bulbar Weakness 30
Pattern 8: Episodic Pain, Weakness, and Myoglobinuria 31
Pattern 9: Episodic Weakness Delayed or Unrelated to Exercise 31
Pattern 10: Stiffness and Decreased Ability to Relax 31
Laboratory approach in the evaluation of a suspected myopathy 32
CK 32
Electrophysiologic Studies 36
The Muscle Biopsy 36
Molecular Genetic Studies 38
Other Tests 38
Summary 39
Web sites 40
References 40
Idiopathic Inflammatory Myopathies 42
Key points 42
Epidemiology 42
Clinical presentation 45
Dermatomyositis 45
Polymyositis 46
Necrotizing Myopathy 46
Conditions associated with dermatomyositis, polymyositis, and necrotizing myopathy 50
Polyarthritis 50
Interstitial Lung Disease 50
Malignancy 50
Autoimmune Necrotizing Myopathy 51
Cardiac Defects 51
Laboratory studies in dermatomyositis, polymyositis, and necrotizing myopathy 51
Cancer Screening 51
Pulmonary Function Testing 52
Biomarker Monitoring 52
Antibody Identification 53
Electrophysiology of dermatomyositis, polymyositis, and necrotizing myopathy 54
Muscle imaging 54
Muscle histopathology and pathogenesis of DM, PM, and NM 55
Dermatomyositis 55
Polymyositis 57
Necrotizing Myopathy 58
Therapy for dermatomyositis, polymyositis, and necrotizing myopathy 59
Corticosteroids 59
Methotrexate 60
Azathioprine 63
Intravenous Immunoglobulin 64
Treatment of Refractory Patients 64
IIM Associated with ILD 65
Promising Therapies 66
Physical Therapy 66
Prognosis 67
References 67
Inclusion Body Myositis 76
Key points 76
Epidemiology 76
Clinical Presentation 77
Associated Conditions 78
Laboratory and Electrophysiologic Testing 79
Muscle Imaging 79
Muscle Histopathology 80
Pathogenesis 81
Diagnostic and research criteria 83
ENMC 2000 84
MRC 2010 84
ENMC 2011 84
Therapy 85
Ongoing Research 86
Prognosis 86
Exercise 89
Summary 89
References 89
Toxic Myopathies 94
Key points 94
Introduction 94
Pathophysiology/Pathogenesis 95
Necrotizing myopathy 95
Introduction 95
Statins 95
Clinical presentation 95
Laboratory features and electrophysiology 97
Histopathology 97
Pathogenesis 97
Treatment 97
Cholesterol-Lowering Drugs (Excluding Statins) 97
Immunophilins 97
Clinical features 98
Laboratory features and electrophysiology 98
Histopathology 98
Pathogenesis 98
Treatment 98
Labetolol 98
Clinical features 98
Laboratory features and electrophysiology 98
Histopathology 98
Pathogenesis 98
Propofol 98
Clinical features 98
Laboratory features 99
Histopathology 99
Pathogenesis 99
Treatment 99
Snake Venom 99
Clinical features 99
Histopathology and pathogeneisis 99
Treatment 99
Amphiphillic drug myopathy (drug-induced autophagic lysosomal myopathy) 99
Chloroquine 99
Clinical features 99
Laboratory features and neurophysiology 100
Histopathology 100
Pathogenesis 100
Hydroxychloroquine 100
Amiodarone 100
Clinical features 100
Laboratory features 100
Histopathology 101
Pathogenesis 101
Treatment 101
Antimicrotubular drug myopathies 101
Colchicine 101
Clinical features 101
Laboratory features 101
Electrophysiologic findings 101
Histopathology 101
Pathogenesis 102
Treatment 102
Vincristine 102
Clinical features 102
Laboratory features 102
Histopathology 102
Pathogenesis 102
Drug-induced mitochondrial myopathies 102
Zidovudine (Azidothymidine) 102
Clinical features 102
Laboratory features 103
Histopathology 103
Pathogenesis 103
Treatment 103
Other Antiviral Agents 104
Drug-induced inflammatory myopathies 104
Cholesterol-Lowering Agents 104
l-tryptophan/Eosinophilia Myalgia Syndrome 104
Clinical features 104
Laboratory features 104
Histopathology 104
Pathogenesis 104
Treatment 105
Toxic oil syndrome 105
d-Penicillamine 105
Cimetidine 105
Procainamide 105
Phenytoin 105
Lamotrigine 106
Interferon Alfa 106
Imatinib Mesylate (Gleevic) 106
Myopathies due to impaired protein synthesis or increased catabolism 106
Steroid Myopathy 106
Clinical features 106
Laboratory and electrophysiologic features 106
Histopathology 107
Pathogenesis 107
Treatment 107
Finasteride 107
Clincal features 107
Laboratory features 107
Electrophysiologic findings 107
Histopathology 107
Pathogenesis 107
Treatment 108
Emetine 108
Clinical features 108
Laboratory features 108
Histopathology 108
Pathogenesis 108
Treatment 108
Toxic myopathies with unknown pathogenic mechanism 108
Acute Quadriplegic Myopathy/Critical Illness Myopathy 108
Clinical features 108
Laboratory features and electrophysiologic findings 109
Histopathology 109
Pathogenesis 109
Treatment 109
Omeprazole 109
Isoretinion 109
Myopathies associated with anesthetic agents and centrally acting medications 109
Malignant Hyperthermia 109
Clinical features 109
Laboratory features and electrophysiologic studies 110
Histopathology 110
Pathogenesis and molecular genetics 110
Treatment 110
Myopathies secondary to drugs of abuse 110
Alcoholic Myopathy 110
Other Drugs 111
Summary 111
References 111
Duchenne and Becker Muscular Dystrophies 118
Key points 118
Introduction 118
Clinical findings 119
Duchenne Muscular Dystrophy 119
Becker Muscular Dystrophy 119
Rating Scales 120
Diagnosis 120
Serum Chemistries 120
Muscle Biopsy 121
Histopathology 121
Assessment of Dystrophin Expression 121
Mutational Analysis 122
Imaging 123
Diagnostic dilemmas 123
Exceptions to the Reading Frame Rule 123
Genetic modifiers 123
Management 124
Management Goals in DMD 124
Pharmacologic therapy 124
Corticosteroids 124
Cardiac Care 125
Nonpharmacologic therapies 125
Pulmonary Care 125
Scoliosis 126
Novel therapies 126
Nonsense Suppression 126
Exon Skipping 126
Gene Transfer 127
Summary 127
References 127
Congenital Myopathies and Muscular Dystrophies 136
Key points 136
Introduction 136
Case 1 137
Case 2 139
Case 3 142
Case 4 145
Case 5 146
Summary 149
References 149
Myotonic Dystrophy 152
Key points 152
Epidemiology 152
Genetics 153
Clinical presentation of Myotonic Dystrophy 154
Congenital DM1 154
Childhood DM1 155
Classical DM1 155
Minimal DM1 155
Neuromuscular features of DM2 155
Systemic features 156
Cardiac Disease 156
Ocular 156
CNS 156
Other Systemic Features 157
Laboratory and electrophysiologic testing 157
Genetic Testing 157
Electrophysiology 157
Muscle Pathology 158
Pathogenesis 158
RNA Toxicity 158
Sequestration of MBNL Proteins 158
Signaling Changes and Aberrant Translation of Expanded Repeats 159
Other Effects 159
Pathophysiology of Congenital DM1 159
Therapy and Management for DM1 and DM2 159
Experimental Treatments for DM1 and DM2 160
References 160
Facioscapulohumeral Muscular Dystrophy 168
Key points 168
Introduction 168
Clinical findings 169
Diagnosis 170
Pathophysiology 171
Therapeutic strategies 172
Summary and future directions 173
References 173
The Limb-Girdle Muscular Dystrophies 176
Key points 176
Introduction 176
LGMD2A—calpain 177
Clinical 177
Laboratory 180
Diagnosis 181
Treatment 181
LGMD2B—dysferlin 181
Clinical 181
Laboratory 182
Diagnosis 182
Treatment 182
LGMD2C–F—a-, ß-, .-, and d-sarcoglycans 183
Clinical 183
Laboratory 184
Diagnosis 184
Treatment 185
LGMD2I—fukutin-related protein 185
Clinical 185
Laboratory 185
Diagnosis 186
Treatment 186
LGMD2L—anoctamin 5 186
Clinical 186
Laboratory 187
Diagnosis 188
Treatment 188
LGMD1B—lamin A/C 188
Clinical 189
Laboratory 189
Diagnosis 189
Treatment 189
Summary 190
References 191
Pompe Disease 198
Key points 198
Introduction 199
Genetic Etiology and Prevalence 200
Clinical presentation 203
Pathogenesis of Pompe disease 204
Newborn screening for Pompe disease 205
The University of Kansas Medical Center case series 205
Discussion, current management, and therapeutic options 212
Summary and future directions 216
Acknowledgments 216
References 216
Metabolic and Mitochondrial Myopathies 224
Key points 224
Introduction 224
Case report 225
Carbohydrate disorders causing exercise-induced symptoms 225
Muscle Phosphorylase Deficiency (McArdle Disease, Glycogen Storage Disease Type V) 225
Pathophysiology 225
Clinical features 225
Diagnosis 226
Management 227
Phosphorylase b Kinase Deficiency (Glycogen Storage Disease Type IX) 227
Pathophysiology 227
Clinical features 227
Diagnosis 228
Management 228
Muscle PFK Deficiency (Tauri Disease, Glycogen Storage Disease Type VII) 228
Pathophysiology 228
Clinical features 228
Diagnosis 228
Management 228
Phosphoglucomutase Deficiency 229
Pathophysiology 229
Clinical features 229
Management 229
Distal Glycolytic Defects 229
Pathophysiology 229
Clinical features 229
Diagnosis 230
Management 230
Other Rare Defects 230
Carbohydrate disorders causing muscle weakness 231
Debrancher Deficiency (Cori Disease, Glycogen Storage Disease Type III) 231
Pathophysiology 231
Clinical features 231
Diagnosis 231
Management 232
Glycogen Branching Enzyme Deficiency (Andersen Disease, GSD Type IV) 232
Pathophysiology 232
Clinical features 232
Diagnosis 232
Management 232
Lipid metabolism disorders causing muscle weakness and lipid accumulation 232
Primary Carnitine Deficiency 232
Pathophysiology 232
Clinical features 233
Diagnosis 234
Management 234
Neutral Lipid Storage Disease 234
Pathophysiology 234
Clinical features 234
Diagnosis 234
Management 234
MADD 234
Pathophysiology 234
Clinical features 234
Diagnosis 235
Management 235
Lipid metabolism disorders causing recurrent myalgia, rhabdomyolysis, and myoglobinuria 235
CPT2 Deficiency 235
Pathophysiology 235
Clinical features 235
Diagnosis 235
Management 236
VLCAD Deficiency 236
Pathophysiology 236
Clinical features 236
Diagnosis 236
Management 236
TP/Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency 236
Pathophysiology 236
Clinical features 236
Diagnosis 236
Management 237
Lipin-1 Deficiency 237
Pathophysiology 237
Clinical features 237
Diagnosis 237
Management 237
Mitochondrial Myopathies 237
mtDNA Mutations 237
Pathophysiology 237
Clinical 237
Diagnosis 239
Mitochondrial Myopathy due to Nuclear Mutations Causing Multiple mtDNA Deletions or mtDNA Depletion 239
Pathogenesis 239
Diagnosis 239
Mitochondrial Myopathy due to Nuclear DNA Mutations Affecting Individual Subunits, Prosthetic Groups, or Respiratory Comple ... 239
Pathophysiology/Clinical 239
Mitochondrial Myopathy due to Defects in Mitochondrial tRNA Translation 240
Pathophysiology/Clinical 240
Diagnosis 240
Management 241
References 241
Muscle Channelopathies 248
Key points 248
Introduction 248
NDM 248
Clinical Features 249
MC 249
PMC 249
Sodium channel myotonias 249
Diagnosis 250
Pathophysiology 250
Therapeutic Options in NDM 251
Congenital myasthenic syndromes 252
Slow-channel CMS 253
Fast-channel CMS 253
Periodic paralyses 253
Clinical Features 253
Hyperkalemic periodic paralysis 253
Hypokalemic periodic paralysis 254
ATS 254
Diagnosis 254
Pathophysiology 256
Therapeutic Options 256
Summary 258
References 258
Distal Myopathies 264
Key points 264
Approach 264
Classic distal myopathies 266
Welander Distal Myopathy: Late Adult Onset, Type 1 266
Tibial Muscular Dystrophy: Late Onset Distal Myopathy Type 2 268
Udd Late Onset Distal Myopathy Type 2a 269
Markesbery-Griggs Late Onset Distal Myopathy Type 2b 270
Nonaka Distal Myopathy: Early Adult Onset, Type 1, Distal Myopathy with Rimmed Vacuoles 270
Miyoshi Distal Myopathy: Early Adult Onset, Type 2 272
Laing Distal Myopathy: Early Onset, Type 3 274
Myofibrillar Myopathy 275
Clinical Manifestations 275
Clinical Manifestations with Mutations 276
Pathologic Alterations 276
Weakness Onset Variability 277
Distal myopathies not yet classified 277
AD Inheritance Late Onset Distal Myopathy 277
AD Weakness of Extremities 278
AD Adult Onset Vacuolar Distal Myopathy 278
AD Adult Onset Slow Progression 279
AD Late Onset 279
Other myopathies with distal weakness 279
Childhood Onset Distal Myopathy 280
Other Muscular Dystrophies 281
Inflammatory Myopathies 281
Metabolic and Congenital Myopathies 282
Myasthenia Gravis 282
References 282
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?
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...
| Erscheint lt. Verlag | 28.8.2014 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Orthopädie | |
| ISBN-10 | 0-323-32038-4 / 0323320384 |
| ISBN-13 | 978-0-323-32038-2 / 9780323320382 |
| Haben Sie eine Frage zum Produkt? |
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