Weiner MD / Tolosa MD / Tolosa Hyperkinetic Movement Disorders

1. Auflage 2012
ISBN: 978-0-444-53487-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 100, 768 Seiten

Reihe: Handbook of Clinical Neurology

The Handbook of Clinical Neurology Vol 100: Hyperkinetic Movement Disorders discusses hyperkinetic disorders related mainly to basal ganglia dysfunction and pathology. It contains 13 sections and 51 chapters written by authoritative and experienced investigators and clinicians in this extremely broad and diverse group of diseases and syndromes. The first section on choreoathetoid diseases and syndromes includes chapters on Huntington's disease and Huntington's disease look-alikes; spinocerebellar degenerations; neuroacanthocytosis; entatorubral-pallidoluysian atrophy; neuroferritinopathy; neurodegeneration with brain iron accumulation; mitochondrial disorders; acquired hepatocerebral degeneration; benign hereditary chorea; and 'senile chorea. The remaining chapters focus on the abnormal involuntary movements associated with each disease or syndrome. These include immune-related chorea, vascular chorea, metabolic disturbances that can induce chorea, chorea in other medical settings (e.g., postpump chorea in children, cancer-related paraneoplastic syndromes), myoclonus, essential tremor, and dystonia, including dystonia plus syndromes. There are also chapters on tardive dyskinesia, unusual clinical syndromes, and tics and stereotyped movements in children. The text is a valuable resource for neurology and psychiatry residents, practicing neurologists and psychiatrists, and specialists in movement disorders. - An authoritative, comprehensive guide to movement disorders - An invaluable reference for the diagnosis and treatment of hyperkinetic diseases and syndromes - High-level discussions that are ideal for specialists in movement disorders, practitioners and residents alike

Autoren/Hrsg.

Weiner MD, William J.

Tolosa MD, Eduardo

Tolosa, Eduardo

Inhaltsverzeichnis

1;Front Cover;1
2;Hyperkinetic Movement Disorders;4
3;Copyright;5
4;Handbook of Clinical Neurology 3rd Series;6
5;Foreword;8
6;Preface;10
7;Dedication;12
8;List of Contributors;14
9;Contents;18
10;Section 1: Choreoathetoid Diseases and Syndromes;22
10.1;Chapter 1: Huntington’s disease – clinical signs, symptoms, presymptomatic diagnosis, and diagnosis;24
10.1.1;History;24
10.1.2;Clinical Manifestations Of huntington's Disease;25
10.1.3;Juvenile-onset Hd;27
10.1.4;The Course of Hd;28
10.1.5;Neurophysiology and Neuroimaging;29
10.1.6;Diagnosis of Hd;30
10.1.7;Presymptomatic (predictive) Testing;31
10.1.8;Summary;31
10.1.9;References;31
10.2;Chapter 2: Huntington’s disease;36
10.2.1;Introduction;36
10.2.2;Epidemiology;36
10.2.3;Genetics and Disease Mechanism;36
10.2.4;Brain Imaging Findings;37
10.2.5;Neurological Symptoms;37
10.2.6;Cognitive Symptoms;37
10.2.7;Psychiatric Symptoms;39
10.2.8;Treatment;41
10.2.9;References;42
10.3;Chapter 3: Molecular biology of Huntington’s disease;46
10.3.1;Introduction;46
10.3.2;Huntington's Disease Genetics;46
10.3.3;Hd Gene Mapping and Identification;46
10.3.4;The huntingtin (Htt) Gene;47
10.3.5;Htt Gene Conservation;47
10.3.6;Htt Gene Promoter and Its Regulation;48
10.3.7;Bidirectional Expression Across a Triplet Cag Repeat;49
10.3.8;Cag Repeat Variability - the Disease-causing Mutation;49
10.3.9;Instability of Cag Repeat and Anticipation;52
10.3.10;Age of Onset Variability;53
10.3.11;Hd Mutation as a Gain Or Loss Of function?;53
10.3.12;Htt MRna Expression and Localization;54
10.3.13;Animal Models of Hd;54
10.3.14;Huntingtin Protein;58
10.3.15;Protein Expression and Localization;59
10.3.16;Nuclear Localization of Huntingtin;60
10.3.17;Posttranslational Modifications Alter Htt Function;60
10.3.18;Proteolytic Processing of Htt;61
10.3.19;Protein Functions;64
10.3.20;Interaction Partners;64
10.3.21;Potential Pathogenic Mechanisms;65
10.3.22;Conclusion;86
10.3.23;References;86
10.4;Chapter 4: Huntington’s disease – neuropathology;104
10.4.1;Introduction;104
10.4.2;Organization of the Basal Ganglia System;104
10.4.3;Neuropathology;107
10.4.4;Clinicopathological Correlation: Juvenile Versus Adult-onset Hd;114
10.4.5;The Occurrence of Features Attributed to Usual Aging in Huntington Disease Brains;115
10.4.6;Phenocopies of Huntington Disease;115
10.4.7;Acknowledgments;116
10.4.8;References;116
10.5;Chapter 5: Huntington’s disease look-alikes;122
10.5.1;Huntington's Disease;122
10.5.2;Huntington's Disease-like Syndromes;123
10.5.3;Other Genetic Causes of Chorea;127
10.5.4;Nongenetic Causes of Chorea;129
10.5.5;Approach to a Patient With Chorea;129
10.5.6;References;130
10.6;Chapter 6: Spinocerebellar degenerations;134
10.6.1;Introduction;134
10.6.2;Dominantly Inherited Ataxias;135
10.6.3;The Typical Dominant Ataxias;136
10.6.4;Recessive Ataxias: Most Common types;152
10.6.5;X-linked Ataxias: Most Common types;154
10.6.6;Sporadic Ataxias;155
10.6.7;References;156
10.7;Chapter 7: Neuroacanthocytosis;162
10.7.1;Introduction;162
10.7.2;Chorea-Acanthocytosis;162
10.7.3;Mcleod Syndrome;164
10.7.4;Huntington's Disease-like 2 (Chapter 5);166
10.7.5;Pantothenate Kinase-associated Neurodegeneration (Chapter 5);167
10.7.6;Other Movement Disorders With Acanthocytosis;168
10.7.7;Therapy;168
10.7.8;Summary;169
10.7.9;References;169
10.8;Chapter 8: Dentatorubral pallidoluysian atrophy;174
10.8.1;Introduction;174
10.8.2;Epidemiology;174
10.8.3;Clinical Features;174
10.8.4;Imaging;176
10.8.5;Genetics;176
10.8.6;Pathology;177
10.8.7;Haw River Syndrome;178
10.8.8;Differential Diagnosis;178
10.8.9;Treatment;179
10.8.10;Conclusion;179
10.8.11;References;179
10.9;Chapter 9: Neurodegeneration with brain iron accumulation;182
10.9.1;Introduction and Overview;182
10.9.2;Neuroferritinopathy;182
10.9.3;Aceruloplasminemia (hereditary Ceruloplasmin Deficiency);185
10.9.4;Pantothenate Kinase-associated Neurodegeneration;186
10.9.5;Infantile Neuroaxonal Dystrophy;188
10.9.6;Idiopathic Nbia;189
10.9.7;A Clinical Approach to Suspected Nbia;190
10.9.8;Acknowledgments;192
10.9.9;References;192
10.10;Chapter 10: Movement disorders and mitochondrial disease;194
10.10.1;Introduction;194
10.10.2;Leigh Syndrome and Leigh-like Syndrome;195
10.10.3;Leber's Hereditary Optic Neuropathy;198
10.10.4;Mohr-Tranebjaerg Syndrome;200
10.10.5;Myoclonus Epilepsy With Ragged-red Fibers;201
10.10.6;Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like Episodes;203
10.10.7;Dna Polymerase Gamma And twinkle;204
10.10.8;Conclusions;206
10.10.9;References;206
10.11;Chapter 11: Acquired hepatocerebral degeneration;214
10.11.1;Introduction and Historical note;214
10.11.2;Clinical Manifestations;214
10.11.3;Etiology;214
10.11.4;Pathophysiology and Pathological Findings;215
10.11.5;Imaging;215
10.11.6;Management;216
10.11.7;Conclusion;217
10.11.8;References;217
10.12;Chapter 12: Benign hereditary chorea;220
10.12.1;Introduction;220
10.12.2;Historical Perspective;220
10.12.3;Epidemiology;220
10.12.4;Classic Bhc;220
10.12.5;Bhc - Entity Or Syndrome? the Queen Square Assessment;222
10.12.6;Genetics;222
10.12.7;Brain-thyroid-lung Syndrome;223
10.12.8;Clinical Spectrum of Neurological Symptoms in Gene-positive Cases;228
10.12.9;Conclusions;232
10.12.10;References;232
10.13;Chapter 13: Senile chorea;234
10.13.1;Incidence;234
10.13.2;Etiology;234
10.13.3;Basal Ganglia Mineralization;237
10.13.4;Investigation of Late-onset Chorea;237
10.13.5;Treatment;237
10.13.6;Conclusion;237
10.13.7;References;237
11;Section 2: Immune-related Chorea;240
11.1;Chapter 14: Sydenham’s chorea;242
11.1.1;Introduction;242
11.1.2;Epidemiology;242
11.1.3;Clinical Features;242
11.1.4;Etiology and Pathogenesis;244
11.1.5;Diagnosis;245
11.1.6;Prognosis and Complications;246
11.1.7;Management;247
11.1.8;Prevention;248
11.1.9;References;248
11.2;Chapter 15: Chorea gravidarum;252
11.2.1;Introduction;252
11.2.2;Epidemiology;252
11.2.3;Clinical Characteristics;252
11.2.4;Etiology;253
11.2.5;Pathophysiology;253
11.2.6;Evaluation;254
11.2.7;Treatment;254
11.2.8;Conclusion;254
11.2.9;References;255
11.3;Chapter 16: Antiphospholipid syndrome and other lupus-related movement disorders;258
11.3.1;Antiphospholipid Syndrome;258
11.3.2;Clinical Features;258
11.3.3;Diagnosis of Aps;259
11.3.4;Risk Factors;259
11.3.5;Treatment;260
11.3.6;Chorea and Aps;260
11.3.7;Aps in Association With Sle;264
11.3.8;Conclusion;264
11.3.9;References;265
12;Section 3: Vascular-related Chorea;268
12.1;Chapter 17: Hemiballismus;270
12.1.1;Introduction;270
12.1.2;Pathophysiology;270
12.1.3;Etiology;272
12.1.4;Clinical Features;275
12.1.5;Prognosis;276
12.1.6;Therapy;276
12.1.7;References;278
12.2;Chapter 18: Vascular chorea in adults and children;282
12.2.1;Introduction;282
12.2.2;Clinical Description;282
12.2.3;Epidemiology;282
12.2.4;Neuroanatomy;282
12.2.5;Etiology;283
12.2.6;Pathophysiology of Vascular Chorea;283
12.2.7;Differential Diagnosis;284
12.2.8;Brain Imaging;285
12.2.9;Prognosis;285
12.2.10;Treatment of Vascular Chorea;285
12.2.11;Conclusion;288
12.2.12;References;288
12.3;Chapter 19: Polycythemia and chorea;292
12.3.1;Introduction;292
12.3.2;Epidemiology, Diagnosis, Genetics, and Environmental Risk Factors of Polycythemia Vera;292
12.3.3;Clinical Manifestations;293
12.3.4;Neurologic Sequelae/polycythemia-induced Movement Disorders;293
12.3.5;Pathophysiology/anatomy of Pv-induced Chorea;294
12.3.6;Imaging and Movement Disorders with Pv;295
12.3.7;Treatment of Pv-induced Movement Disorders;295
12.3.8;Summary;295
12.3.9;References;296
13;Section 4: Metabolic Disturbances;298
13.1;Chapter 20: Hyperthyroid chorea;300
13.1.1;Introduction;300
13.1.2;Epidemiology;300
13.1.3;Clinical Features;301
13.1.4;Chorea: Onset, Severity and Distribution;301
13.1.5;Pathophysiology;303
13.1.6;Conclusion;305
13.1.7;References;306
13.2;Chapter 21: Hyperglycemic nonketotic states and other metabolic imbalances;308
13.2.1;Chorea Associated With Nonketotic Hyperglycemia;308
13.2.2;Hypoglycemia;310
13.2.3;Calcium Disorders;311
13.2.4;Hypernatremia;311
13.2.5;References;311
14;Section 5: Chorea in Other Medical Settings;314
14.1;Chapter 22: Postoperative encephalopathy with choreoathetosis;316
14.1.1;Introduction;316
14.1.2;Surgical Repair of Congenital Heart Disease;316
14.1.3;Postoperative Development Of choreoathetosis;317
14.1.4;Diagnostic Evaluation of Postpump Choreoathetosis;318
14.1.5;Treatment of Postpump Choreoathetosis;320
14.1.6;Risk Factors for Development Of postpump Choreoathetosis;320
14.1.7;Theories of Pathogenesis;322
14.1.8;Neurologic Outcomes of Children With Postpump Choreoathetosis;323
14.1.9;Alternative Surgical Techniques and Neuroprotective Strategies;323
14.1.10;Conclusion;325
14.1.11;References;325
14.2;Chapter 23: Movement disorders in patients with multiple sclerosis;328
14.2.1;Introduction;328
14.2.2;Movement Disorders in Multiple sclerosis;328
14.2.3;Conclusion;332
14.2.4;References;333
14.3;Chapter 24: Paraneoplastic syndromes causing movement disorders;336
14.3.1;Introduction;336
14.3.2;General Concepts;336
14.3.3;Sensory Neuronopathy and Pseudoathetoid Movements;337
14.3.4;Encephalomyelitis and Chorea;337
14.3.5;Brainstem Encephalitis And hypokinesis;338
14.3.6;Encephalitis With Stereotyped Complex Movements and Nmda Receptor Antibodies;338
14.3.7;Paraneoplastic Cerebellar Degeneration and Tremor;339
14.3.8;Opsoclonus-myoclonus;339
14.3.9;Stiff-person Syndrome;339
14.3.10;Neuromyotonia Or Isaacs' Syndrome;340
14.3.11;Management of Paraneoplastic Syndromes;340
14.3.12;References;341
14.4;Chapter 25: Hyperkinetic movement disorders associated with HIV and other viral infections;344
14.4.1;Introduction;344
14.4.2;Hiv and Aids;344
14.4.3;Hyperkinetic Movement Disorders in Hiv-infected Patients;345
14.4.4;Chorea and Hemichorea-hemiballism;346
14.4.5;Dystonia;347
14.4.6;Tremor;347
14.4.7;Myoclonus;348
14.4.8;Neuroimaging;348
14.4.9;Pathogenetic Mechanisms;348
14.4.10;Other Viral Infections Associated With Hyperkinetic Movement Disorders;349
14.4.11;EncephalItis Lethargica;349
14.4.12;Flavivirus Infections;350
14.4.13;West Nile Virus;350
14.4.14;Japanese Encephalitis Virus;351
14.4.15;Herpes Simplex Encephalitis;351
14.4.16;Prion Diseases;352
14.4.17;Kuru;352
14.4.18;Creutzfeldt-jakob Disease;352
14.4.19;Acknowledgment;353
14.4.20;References;353
14.5;Chapter 26: Chorea caused by toxins;356
14.5.1;Introduction;356
14.5.2;Drugs of Abuse;356
14.5.3;Conclusion;364
14.5.4;Acknowledgment;364
14.5.5;References;364
14.6;Chapter 27: Drug-induced hyperkinetic movement disorders by nonneuroleptic agents;368
14.6.1;Introduction;368
14.6.2;Chorea;368
14.6.3;Dystonia;376
14.6.4;Tics;378
14.6.5;Tremor;378
14.6.6;Myoclonus;380
14.6.7;Conclusion;380
14.6.8;References;380
15;Section 6: Other Syndromes;386
15.1;Chapter 28: Paroxysmal choreodystonic disorders;388
15.1.1;Introduction;388
15.1.2;Paroxysmal Kinesigenic Dyskinesia;388
15.1.3;Paroxysmal Nonkinesigenic Dyskinesia;391
15.1.4;Paroxysmal Exertion-induced Dyskinesia;392
15.1.5;References;393
15.2;Chapter 29: Painful legs and moving toes;396
15.2.1;Introduction;396
15.2.2;Clinical and Electrophysiologic Features;396
15.2.3;Localization and Associated Conditions;398
15.2.4;Differential Diagnosis;400
15.2.5;Treatment;401
15.2.6;References;402
16;Section 7: Athetosis;406
16.1;Chapter 30: Birth-related syndromes of athetosis and kernicterus;408
16.1.1;Introduction;408
16.1.2;Clinical Features of Athetosis;409
16.1.3;Etiology of Athetosis;410
16.1.4;Bilirubin Encephalopathy;411
16.1.5;Athetoid Cerebral Palsy;414
16.1.6;Conclusion;414
16.1.7;References;415
17;Section 8: Myoclonus;418
17.1;Chapter 31: Myoclonus;420
17.1.1;Introduction;420
17.1.2;Clinical Classification and Etiologies;421
17.1.3;Physiological Characteristics;429
17.1.4;Animal Model;432
17.1.5;Evaluation;432
17.1.6;Therapy;434
17.1.7;References;436
17.2;Chapter 32: Startle syndromes;442
17.2.1;The Normal Human Startle reflex;442
17.2.2;Startle Syndromes;443
17.2.3;Hyperekplexia;444
17.2.4;Startle Epilepsy;447
17.2.5;Neuropsychiatric Startle Syndromes;448
17.2.6;Conclusion;448
17.2.7;References;449
18;Section 9: Essential Tremor;452
18.1;Chapter 33: Essential tremor;454
18.1.1;Introduction: a Changing Landscape;454
18.1.2;Tremor in Human History And origins of the Term essential Tremor;454
18.1.3;Epidemiology and Genetics;455
18.1.4;Pathophysiology;456
18.1.5;Clinical Presentation and Natural History;458
18.1.6;Diagnosis;461
18.1.7;Conclusion;464
18.1.8;Acknowledgment;464
18.1.9;References;464
18.2;Chapter 34: Management of essential tremor, including medical and surgical approaches;470
18.2.1;Severity Assessment of Essential tremor;470
18.2.2;Approach to Treatment;471
18.2.3;Psychological and Social Support;475
18.2.4;Alternative Measures and Lifestyle Changes;475
18.2.5;Conclusions;475
18.2.6;References;475
18.3;Chapter 35: Orthostatic tremor – a review;478
18.3.1;Introduction;478
18.3.2;Clinical Spectrum of Orthostatic Tremor - Syndromic Associations;478
18.3.3;Progression;479
18.3.4;Differential Diagnosis;480
18.3.5;Pathophysiology;480
18.3.6;Treatment;481
18.3.7;Summary;481
18.3.8;References;482
19;Section 10: Dystonia;484
19.1;Chapter 36: Early-onset primary dystonia;486
19.1.1;History;486
19.1.2;Clinical Features;487
19.1.3;Early-onset Primary Dystonia;489
19.1.4;Dyt-1 (Tor1A) Early-onset Dystonia;489
19.1.5;Early-onset Primary Dystonia, Non-Dyt1;491
19.1.6;Early-onset Primary Dystonia - Autosomal-recessive;491
19.1.7;Pathophysiology of Dystonia;492
19.1.8;Diagnosis;493
19.1.9;Treatment;495
19.1.10;Conclusion;496
19.1.11;References;496
19.2;Chapter 37: Adult-onset dystonia;502
19.2.1;Introduction;502
19.2.2;Epidemiology of Focal Dystonia;502
19.2.3;Cranial Dystonia (blepharospasm-oromandibular Dystonia Syndrome);503
19.2.4;Cervical Dystonia;510
19.2.5;Writer's Cramp Dystonia;511
19.2.6;Neuroanatomy and Neurophysiology;513
19.2.7;Pathology of Primary Focal Dystonias;517
19.2.8;Treatment;518
19.2.9;Future and Summary;524
19.2.10;Acknowledgment;524
19.2.11;References;524
19.3;Chapter 38: Nonprimary dystonias;534
19.3.1;Classification of Dystonias;534
19.3.2;Prevalence;534
19.3.3;Secondary Dystonias;534
19.3.4;Dystonia-plus Syndromes (chapters 39-41);541
19.3.5;Heredodegenerative Dystonia;542
19.3.6;Diagnosis of Nonprimary Dystonias;547
19.3.7;Treatment of Nonprimary Dystonias;547
19.3.8;References;551
19.4;Chapter 39: Dopa-responsive dystonia;560
19.4.1;Introduction;560
19.4.2;Autosomal-dominant Gtp Cyclohydrolase 1 Deficiency (segawa Disease): Dominant Dyt5;560
19.4.3;Recessive Deficiency of the Enzymes of Pteridine Metabolism;568
19.4.4;Recessive Tyrosine Hydroxylase Deficiency;570
19.4.5;DyT14;572
19.4.6;Juvenile Parkinsonism, Parkinsonism-dystonia Complex;572
19.4.7;Summary;573
19.4.8;References;573
19.5;Chapter 40: Rapid-onset dystonia-parkinsonism;580
19.5.1;Clinical Presentation;580
19.5.2;Molecular Genetics;580
19.5.3;Other Diagnostic Testing;581
19.5.4;Differential Diagnosis;581
19.5.5;Natural History;582
19.5.6;Management;582
19.5.7;References;582
19.6;Chapter 41: Myoclonus-dystonia syndrome;584
19.6.1;Introduction;584
19.6.2;Inherited Myoclonus-dystonia;584
19.6.3;Primary Dystonias With Myoclonus ("myoclonic Dystonia");590
19.6.4;Autosomal-dominant Gtpch Deficiency (dyt5 Dystonia);591
19.6.5;Vitamin E Deficiency;591
19.6.6;Differential Diagnosis;591
19.6.7;References;592
20;Section 11: Tardive Dyskinesia;598
20.1;Chapter 42: Typical and atypical neuroleptics;600
20.1.1;Introduction;600
20.1.2;From the History of Psychotropic Drugs to Tardive Dyskinesia;600
20.1.3;Definition and Clinical Overview;602
20.1.4;Epidemiology and Risk Factors;606
20.1.5;Pathophysiology;609
20.1.6;Treatment and Management;612
20.1.7;References;614
20.2;Chapter 43: Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs;622
20.2.1;Introduction;622
20.2.2;Epidemiology of Tardive Dyskinesia Risk With Older Neuroleptics;623
20.2.3;Risk Factors for Tardive Dyskinesia;625
20.2.4;Epidemiology of Tardive Dyskinesia in the Era of Modern antipsychotics;626
20.2.5;Is Risk of Tardive Dyskinesia Declining?;631
20.2.6;Effects of Expanding Applications of Modern Antipsychotics;632
20.2.7;Conclusions;632
20.2.8;Acknowledgments;633
20.2.9;References;633
20.3;Chapter 44: Unusual focal dyskinesias;638
20.3.1;Introduction;638
20.3.2;Ear Dyskinesias;638
20.3.3;Lip, Chin, and Jaw Dyskinesias;639
20.3.4;Focal Tongue Dyskinesias;640
20.3.5;Belly Dancer's Dyskinesia;641
20.3.6;Back Dyskinesias;642
20.3.7;Scapula Dyskinesias;642
20.3.8;Limb Dyskinesias;644
20.3.9;Painful Legs and Moving Toes;644
20.3.10;Movements of Amputation Stumps;644
20.3.11;Summary;645
20.3.12;References;645
21;Section 12: Tics;650
21.1;Chapter 45: Stereotypic movement disorders;652
21.1.1;Introduction;652
21.1.2;Definition;652
21.1.3;Clinical Characteristics;653
21.1.4;Differentiating Stereotypies;653
21.1.5;Classification;654
21.1.6;Pathophysiology;656
21.1.7;Therapy;658
21.1.8;Conclusion;658
21.1.9;References;658
21.2;Chapter 46: Tourette syndrome and other tic disorders;662
21.2.1;Historical Features;662
21.2.2;Phenomenology of Tics;662
21.2.3;Tic Characteristics;663
21.2.4;Tic Diagnoses;663
21.2.5;Course of Tics;665
21.2.6;Associated Behaviors;665
21.2.7;Treatment of Tics;667
21.2.8;Etiology;669
21.2.9;Neurobiology;670
21.2.10;References;672
22;Section 13: Other Syndromes;680
22.1;Chapter 47: Restless legs syndrome;682
22.1.1;Description and Epidemiology;682
22.1.2;Health-related Significance Of restless Legs Syndrome;683
22.1.3;Genetics of Restless Legs Syndrome;684
22.1.4;The Significance of Periodic Limb Movements of Sleep;685
22.1.5;Pathophysiology of Rls/Plms;685
22.1.6;Localization of Rls Pathology Within the Nervous System;686
22.1.7;Treatment;687
22.1.8;Treatment Complications;689
22.1.9;Treatment in Special Clinical Situations;690
22.1.10;References;690
22.2;Chapter 48: Hemifacial spasm;696
22.2.1;Epidemiology;696
22.2.2;Clinical Features;696
22.2.3;Etiology;697
22.2.4;Pathophysiology;698
22.2.5;Investigations;698
22.2.6;Differential Diagnosis;699
22.2.7;Treatment;699
22.2.8;References;700
22.3;Chapter 49: Wilson’s disease;702
22.3.1;Historical Aspects;702
22.3.2;Genetics;702
22.3.3;Epidemiology;703
22.3.4;Pathophysiology;704
22.3.5;Clinical Features;704
22.3.6;Diagnostic Evaluation of Wd;711
22.3.7;Diagnostic Testing Guidelines;715
22.3.8;Treatment;715
22.3.9;Treatment Guidelines;719
22.3.10;References;720
22.4;Chapter 50: Task-specific tremor;732
22.4.1;Definition;732
22.4.2;Primary Writing Tremor;732
22.4.3;Other Task-specific Tremors;737
22.4.4;Conclusion;737
22.4.5;References;738
22.5;Chapter 51: Hyperkinetic psychogenic movement disorders;740
22.5.1;Introduction;740
22.5.2;Terminology;740
22.5.3;Epidemiology;740
22.5.4;Diagnosis;741
22.5.5;Psychogenic Tremor;742
22.5.6;Psychogenic Dystonia;744
22.5.7;Psychogenic Myoclonus;745
22.5.8;Other Psychogenic Hyperkinetic Movement Disorders;746
22.5.9;Psychiatric Diagnoses in Pmd;746
22.5.10;Pathophysiology;746
22.5.11;Treatment;747
22.5.12;Prognosis;748
22.5.13;References;748
23;Index;752

Leseproben

, Vol. 100, No. Suppl C, 2011

ISSN: 0072-9752

doi: 10.1016/B978-0-444-52014-2.00001-X

Chapter 1Huntington’s disease – clinical signs, symptoms, presymptomatic diagnosis, and diagnosis

Kathleen M. Shannon*

Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

*Correspondence to: Kathleen M. Shannon, M.D., Professor, Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison Street, Suite 755, Chicago, IL 60612, USA. Tel: [phone], Fax: [phone],

E-mail address: [e-mail]

History

The hereditary chorea, as I shall call it, is confined to certain and fortunately a few families, and has been transmitted to them, an heirloom from generations away back in the dim past.

(George Huntington, 1872)

George Huntington was not the first to describe the disease that now bears his name. In 1842, CO Waters described an affliction known colloquially in southeastern New York as “the magrums (or migrims),” consisting of “spasmodie action of all or nearly all the voluntary muscles of the system – of involuntary and more or less irregular motions of the extremities, face and trunk” (Waters, 1842). Later, Lund (1860) (DeJong, 1973) described the “twitches,” a hereditary and progressive movement disorder, sometimes with dementia. Lyon (1863) similarly recounted that this affliction was recognized as hereditary, “and the people among whom it occurs believe this to constitute its only legitimate method of propogation, and acting accordingly, have repeatedly been known to interdict marriage alliances between their children and those believed to be tainted with the megrim diathesis under the severe penalty of social ostracism” (Lyon, 1863). In 1872, George Huntington presented his now famous paper describing families at the eastern end of Long Island. His cogent description included its hereditary nature, tendency to insanity and suicide, and onset in adulthood, and led Osler to comment: “In the history of medicine there are few instances in which a disease has been more accurately, more graphically or more briefly described” (Osler, 1908). Osler’s paper (1894) describes two Huntington’s families, including Family X, a couple who lived into the ninth decade without developing the disease, but two of whose 11 children and subsequent descendants developed the disease (Fig. 1.1). This may represent the first report of disease related to parental premutation expansion.

Fig. 1.1 Pedigree of family presented in Osler’s monograph (Osler, 1894).

Huntington did not recognize the juvenile phenotype of Huntington’s disease (HD). A typical case had been reported by Lyon in 1863, and onset under the age of 10 was first reported by Harbison in 1880. Following Westphal’s presentation of a case with onset at 18, the rigid-akinetic juvenile phenotype became known as the Westphal variant (Westphal, 1883). Caudate atrophy and neuronal degeneration in HD were described by Anton in 1896.

In 1952, Dr. Americo Negrette arrived in the rural suburbs of Maracaibo, Venezuela for his second official medical job. Just days after his arrival, he encountered a boy staggering and falling in the streets. Though he thought the boy was drunk, he learned the boy was “a sanvitero,” a sufferer of St. Vitus’ dance. Despite their history of criminal and behavioral irregularities, Negrette was fascinated by the sanviteros, and he visited their neighborhood often. His visits led him to conclude that sanvitero was actually HD. Over time, Negrette catalogued many of the physical and behavioral characteristics of HD, and in 1955 he wrote (Negrette, 1962). Negrette’s discovery languished for nearly two decades, until Ramon Avila-Giron, a former student, presented films of Venezuelan choreics at the 1972 Centennial Symposium on HD in Ohio. Although skeptical at first, the HD research community embraced these findings, launching a research effort that included annual visits to the Venezuela kindreds (Okun and Thommi, 2004). Extensive clinical and genetic analysis of these kindreds led to great discoveries about the disease and its genetics, including the discovery in 1983 of a polymorphic DNA marker linked to the HD gene (Gusella et al., 1983). For the first time, predictive testing was available, although the need for a significant kindred available for testing, and diagnostic uncertainty due to recombination reduced the usefulness of the test (Almqvist et al., 1997). In 1993, the gene was isolated and found to be an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat expansion at the distal end of the fourth chromosome (4p16). Fully penetrant HD is associated with CAG repeat lengths >  39; incomplete penetrance is seen with CAG repeat lengths between 36 and 39; and those with CAG repeat lengths between 29 and 35 are considered potentially unstable premutations (Table 1.1). Early onset is associated with very large repeat expansions. It then became possible to diagnose accurately symptomatic patients and identify those destined to fall ill with the disease (The Huntington’s Disease Collaborative Research Group, 1993). In addition, the discovery of the gene led to the rapid development of multiple animal models of the disease, increased knowledge of its pathogenesis, and ultimately to rational clinical trials of disease modification in HD.

Table 1.1 CAG repeat lengths in gene

Repeat length

<  27

Normal

27–35

Nonpenetrant with paternal meiotic instability

36–39

Reduced penetrance with paternal meiotic instability

>  39

Huntington’s disease

Clinical manifestations of huntington’s disease

HD causes clinical manifestations in three domains of function: (1) motor; (2) cognitive; and (3) behavioral and psychiatric (Walker, 2007). Within these domains, early signs of HD are notoriously protean (Table 1.2), and related in part to age at onset, with a particularly prominent juvenile phenotype (Aubeeluck and Brewer, 2008). Behavioral and psychiatric changes will be discussed in Chapter 2, while this chapter focuses on motor and cognitive changes.

Table 1.2 Motor and cognitive signs in Huntington’s disease

Early	Middle	Late

Slow/delayed saccades Clumsiness/fidgetiness Chorea Dysarthria Hyperreflexia Inattentiveness Disorganization Executive dysfunction

Chorea Dystonia Dysarthria Dysphagia Dropping things Motor impersistence Bradykinesia Rigidity Poor manual dexterity Imbalance Gait disorder Intellectual decline Memory loss Poor communication Sleep disorder Inflexibility Weight loss

Chorea Bradykinesia Rigidity Frequent falls Severe gait disorder Severe dysphagia Severe dysarthria Global dementia Incontinence Weight loss

By convention, the clinical diagnosis of HD is made when there are clear signs of a motor illness consistent with the diagnosis. This does not negate the importance of early behavioral and cognitive changes, but speaks to the lower specificity of these signs as markers of disease onset.

Motor changes

With typical adult onset, HD affects every aspect of motor function, yet the clinical picture can be highly variable. Chorea is the sign that typically leads to a clinical diagnosis. Early chorea may be subtle, and the patient may appear anxious or fidgety. Indeed, even experts may not agree on the presence of early or mild chorea (de Boo et al., 1998). Common choreic movements in HD include raising or lowering the eyebrows, winking, lip pursing or mouthing movements, head movements, shoulder lifting, abdominal muscle contraction, rocking of the pelvis, piano-playing movements of the fingers, and abduction or adduction of the thighs, or ankle or toe movements (Jankovic and Lang, 2008). Choreic movements in HD often flow or are incorporated into voluntary movements. Voluntary movements themselves may appear exaggerated or flamboyant. Chorea typically increases in severity during the early phases of HD, and may often stabilize in middle stages of the illness. Dystonia is present in nearly all HD patients, with moderate severity in more than half and severe movements in nearly 20%, though for the typical patient it appears later in the illness than does chorea. The most common dystonic movements are internal rotation of the shoulder, fist clenching, excessive knee flexion during ambulation, and foot inversion. Dystonia can often be partially suppressed, but becomes progressively more severe over time...