Huntington¿s Chorea

It is a pleasure to send Dr. Hayden's monograph on its way to as yet unknown but hopefully widespread destinations with all the valedictions a Foreword may contain. Since I met the author in Cape Town in 1978 I have been struck, on numerous occasions, by the fortuitous combination of an inquisitive mind, a creative drive, a sharp awareness of the historical and social setting of phenomena, and a solid discipline which his personality displays behind a good-natured laugh. If a tree is known by its fruits, both Dr Hayden's PhD thesis and the present monograph afford quite an insight into the auctor intellectualis. The amalgamation of the terrible mise ry behind scientifIc facts and the elegantly artistic presentation of this book will leave none of its readers unperturbed. It reminds me of Nietzsche's 'Denn das Schöne ist nichts als des Schrecklichen Anfang, und wir bewundern es so weil es gelassen verschmäht uns zu zerstören' (Beauty is but Horror's beginning, and we admire it because it resignedly spurns to destroy us). The book is a denial, a testimony against Juvenal's spurious 'Sternmata quid faciunt ... ' (of what value are pedigrees). For it is the very genetical prolongation of misery over the centuries that brought Huntington's chorea to South Africa, Australia and the USA from the shores of sea-faring seventeenth-century England and Holland.

1 Historical Background.- 1.1. Chorea in the Middle Ages: The Dancing Mania.- 1.2. Thomas Sydenham and Chorea.- 1.3. From Sydenham to Huntingdon: The First Descriptions of Inherited Chorea.- 1.4. Huntington’s Chorea.- 2 Genealogy and Geographic Distribution.- 2.1. Genealogical Methods.- 2.2. Genealogical Investigations in Various Parts of the World.- 2.2.1. United States of America.- 2.2.2. South Africa.- 2.2.3. Canada.- 2.2.4. Australia.- 2.2.5. The Caribbean.- 2.2.6. The Indian Subcontinent.- 2.2.7. Venezuela.- 2.2.8. Moray Firth Area of Scotland.- 2.2.9. Japan.- 2.3. The Importance of Genealogical Investigations.- 2.4. The Original Source of the Gene for Huntington’s Chorea.- 3 Epidemiology.- 3.1. Diagnostic Critera.- 3.2. Prevalence.- 3.2.1. Problems in the Comparison of Prevalence Data.- 3.2.2. Areas of High Prevalence: Possible Contributing Factors.- 3.2.3. Areas of Low Prevalence: Possible Contributing Factors.- 3.3. The Epidemiology of Juvenile Huntington’s Chorea.- 3.4. Incidence.- 3.4.1. International Comparison.- 3.5. Mortality Data.- 3.5.1. International Comparison.- 4 Natural History.- 4.1. Age at Onset.- 4.1.1. International Comparison.- 4.1.2. The Relevance of Age at Onset to Genetic Counselling.- 4.2. Age at Death.- 4.2.1. International Comparison.- 4.3. Duration.- 4.4. Factors Modifying the Action of the Gene.- 4.4.1. Genetic Considerations.- 4.4.2. Environmental Factors.- 5 Clinical Features.- 5.1. The Presenting Symptoms and Signs.- 5.2. General Manifestations.- 5.3. Neurological Features.- 5.3.1. Chorea.- 5.3.2. Hypertonicity: Rigidity and Spasticity.- 5.3.3. Dysarthria.- 5.3.4. Dysphagia.- 5.3.5. Disturbance of Gait.- 5.3.6. Oculomotor Dysfunction.- 5.3.7. Epilepsy.- 5.3.8. Incontinence.- 5.3.9. Cerebellar Signs.- 5.3.10. Other Neurological Signs.- 5.4. Mental Disturbance.- 5.4.1. Dementia.- 5.4.2. Affective Disturbance.- 5.4.3. Change of Personality.- 5.4.4. Schizophreniform Psychosis.- 5.4.5. Other Psychiatric Symptoms.- 5.5. Staging.- 5.6. Variants.- 5.6.1. The Westphal Variant.- 5.6.2. Juvenile Huntington’s Chorea.- 5.6.3. Other Variants.- 5.7. The Clinical Features of Juvenile Huntington’s Chorea.- 5.8. Diagnostic Techniques.- 5.8.1. Electroencephalographic Studies (EEG).- 5.8.2. Pneumoencephalographic Studies (PEG).- 5.8.3. Computerised Axial Tomography (CAT).- 5.8.4. Cerebral Angiography.- 5.9. Problems of Diagnosis.- 5.9.1. Misdiagnosis.- 5.9.2. The Differential Diagnosis of Inherited Chorea.- 6 Neuropathology.- 6.1. Gross Pathology.- 6.2. Findings on Light Microscopy.- 6.2.1. Leptomeninges.- 6.2.2. Cerebral Cortex.- 6.2.3. The Caudate Nucleus and Putamen.- 6.2.4. Pathological Changes in Other Parts of the NervousSystem.- 6.3. Ultrastructural Features.- 6.3.1. Cerebral Cortex.- 6.3.2. The Striatum.- 6.4. The Importance of Post-mortem Examination.- 6.5. The Brain and Tissue Bank.- 7 Genetics.- 7.1. Mutations.- 7.2. Heterozygote Frequency.- 7.3. The Homozygous Form.- 7.4. Heterogeneity.- 7.5. Unusual Aspects of the Genetics of Juvenile Huntington’s Chorea Ill.- 7.5.1. Predominance of Paternal Descent Ill.- 7.5.2. Familial Aggregation.- 7.6. Genetic Registers.- 7.7. Genetic Counselling.- 7.8. Reproductive Fitness.- 8 Living with Huntington’s Chorea: The Social Perspective.- 8.1. Psychosocial Consequences for the Affected Person.- 8.1.1. Psychological Defence Mechanisms.- 8.1.2. Suicide.- 8.1.3. Coping: Guidelines for Management.- 8.2. The Experience of Being At Risk.- 8.2.1. Some Guidelines for Counselling Those At Risk.- 8.2.2. Marriage and Parenthood: The Options.- 8.3. The Burden on the Unaffected Spouse.- 8.4. Huntington’s Chorea: A Family Disease.- 8.5. Antisocial Behaviour: Huntington’s Chorea and the Law.- 8.6. The Economic Burden.- 9 Management.- 9.1. A Rational Approach to Pharmacotherapy.- 9.1.1. Chorea.- 9.1.2. Rigidity.- 9.1.3. Epilepsy.- 9.1.4. Dementia.- 9.1.5. Affective Disturbance.- 9.1.6. Psychosis.- 9.2. Surgery.- 9.3. Other Therapeutic Modalities.- 9.3.1. Physical Therapy.- 9.3.2. Speech Therapy.- 9.3.3. Occupational Therapy.- 9.3.4. Nutrition.- 9.3.5. Nursing Care.- 9.3.6. Social Work.- 9.3.7. Psychotherapy.- 9.3.8. Lay Groups.- 9.4. Future Prospects.- 10 Current Trends in Research.- 10.1. A Unifying Conceptual Approach.- 10.2. Investigations of the Abnormal Gene.- 10.3. The Search for the Altered Gene Product.- 10.4. The Investigation of Disturbed Cell Function/Structure.- 10.4.1. Membrane Abnormalities.- 10.4.2. Fibroblast Activity.- 10.4.3. Immunological Abnormalities.- 10.5. Viruses.- 10.6. Neurochemistry.- 10.6.1. Dopamine.- 10.6.2. Gamma-aminobutyric acid (GABA).- 10.6.3. Acetylcholine.- 10.6.4. Serotonin.- 10.6.5. Peptides.- 10.6.6. Neurotransmitter Receptor Abnormalities.- 10.7. Neuroendocrine Disturbances.- 10.8. Predictive Tests.- 10.8.1. Ethical Dilemmas.- 10.8.2. Attempts at Presymptomatice Diagnosis.- 10.9. Conclusion.- Appendixes.- 1. The Use of Conditional Probabilities in Genetic Counselling for Huntington’s Chorea.- 2. Method for Determination of the Mutation Rate in Huntington’s Chorea...- 3. Method for Determination of the Heterozygote Frequency in Huntington’s Chorea.- 4. Name of Addresses of Lay Organisations and Other Centres for Information on Huntington’s Chorea.- 5. Brain Donation Programme.