Marsden FRCS / Fahn MD Movement Disorders

Neurology
1. Auflage 2013
ISBN: 978-1-4831-6314-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 394 Seiten

Neurology, Volume 2: Movement Disorders is a part of an international series of critical reviews of topics in neurology. This volume focuses on Parkinsonism and dyskinesia, a condition characterized by abnormal involuntary movements. Organized into 18 chapters, this book first elucidates the problems, causes, pathology, brain neurotransmitter changes and receptors, depression, dementia, fluctuations of disability, and treatment of Parkinson's disease. Subsequent chapters then explore the problems, controversies, and surgical approaches involved in certain dyskinesias. The role of dopamine receptors in movement disorders is also explored. This book will be valuable to neurologists-in-training, as well as to those in research field or in practice in this field of interest. The book's clinical content will help in the management of patients with movement disorders.

Autoren/Hrsg.

Marsden FRCS, DSc

Fahn MD, Stanley

Leseproben

1

Problems in Parkinson’s disease

C.D. Marsden and Stanley Fahn

Publisher Summary

This chapter discusses problems in Parkinson’s disease. The management of Parkinson’s disease today is a complex and demanding affair. Although peripherally acting dopa decarboxylase inhibitors have markedly reduced the incidence of anorexia, nausea, and vomiting provoked by levodopa, this still remains a major problem in a minority of patients. The sudden cessation of levodopa in a patient who has taken the drug for many years may cause a confusing akinetic coma-vigil state, which can easily be reversed by reintroducing levodopa, if necessary, by a nasogastric tube. Commonly, those developing mental changes already have early or obvious dementia. Most patients with Parkinson’s disease or postencephalitic Parkinsonism show some response to levodopa.

INTRODUCTION

The management of Parkinson’s disease today is a complex and demanding affair. The individual patient often poses a changing sequence of different problems, each demanding separate attention. There has been a considerable increase in knowledge about all aspects of Parkinson’s disease in the last decade. The editors have chosen certain topics for presentation in separate chapters because of their interest and importance to understanding of the disease, and because there is now a substantial body of information to discuss on each of these topics.

Although the cause of Parkinson’s disease still is not known, useful, if negative, information has been obtained in the fields of epidemiology, virology and genetics, as is discussed in Chapter 2 by Roger Duvoisin. Any understanding of the etiology of Parkinson’s disease must depend upon a thorough knowledge of the pathology of the condition. In Chapters 3, 4 and 5 respectively, Lysia Forno reviews the histopathology; Oleh Hornykiewicz, the changes in neurotransmitter chemistry; and Urpo Rinne, the alterations of receptors in the brain.

The clinical features of Parkinson’s disease generally are well-known, but the extent to which intellectual and affective disorders are inherent to the condition is controversial. Richard Mayeux in Chapter 6 reviews the evidence available on these topics, which are increasingly being discussed in the literature.

The routine drug treatment of Parkinson’s disease does not require repetition. However, all practitioners are faced with the difficult problem of emergence of fluctuations of response during chronic therapy. In Chapters 7 and 8 the editors discuss and categorize, along with David Parkes and Niall Quinn (Chapter 7), the clinical features and pathophysiology of such fluctuations.

Many new drugs, other than anticholinergics, amantadine, and levodopa preparations, are being tested in Parkinson’s disease. New directly-acting dopamine agonists are proving their value when levodopa fails. Bromocriptine is now in routine use in Europe, and newer ergoline derivatives are under extensive clinical trial. The practitioner must find it difficult to assess the relative worth of these different directly-acting agonists; Abe Lieberman and Menek Goldstein survey this field in Chapter 9. Deprenyl is another new drug, on which sufficient experience has been gained in Europe to assess its role, as is discussed in Chapter 10 by Merton Sandler and Gerald Stern.

The many variants of the ‘akinetic-rigid syndrome’ often cause diagnostic confusion. Roger Bannister and David Oppenheimer discuss the interrelationship of idiopathic orthostatic hypotension, the Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar degeneration, and their concept of ‘multiple system atrophy’, which links these entities, in Chapter 11.

Many other practical problems that face the practitioner in the management of a patient with Parkinson’s disease are not discussed, because it is difficult to provide a definitive statement on these matters. To cover these gaps, and to give some guidance on present views, the editors state their own approach to coping with some of these problems.

WHEN SHOULD LEVODOPA TREATMENT BE STARTED?

On theoretical grounds, one could take opposite views on whether to start levodopa treatment at the time of diagnosis. On the one hand, it could be argued that early treatment, by replenishing the missing neurotransmitter, may reverse changes in the postsynaptic dopamine receptors which are responsible for some of the problems in the management of the disease. On the other hand, it has been argued that levodopa itself is toxic. This may come about in one of two ways: saturating the brain with levodopa might lead to the formation of unnatural neurotoxic metabolites such as 6-hydroxydopamine, or could lead to excess formation of naturally-occurring, but neurotoxic intermediaries in the dopaquinone-melanin pathway. There is no convincing human or experimental evidence for any of these suggestions, so we have to turn to the clinical evidence to decide one way or the other.

Unfortunately, this too is controversial. On the one hand, Lesser 3 claim by retrospective analysis of their population of patients that chronic treatment with levodopa is detrimental. They base this conclusion on finding that the level of disability after chronic therapy is related more to the duration of treatment than to the duration of the disease. On the other hand, Markham and Diamond4 claim exactly the opposite.

Until this dilemma is solved by further studies, the editors advise their patients to delay levodopa therapy until disability warrants it. The judgment as to when that point is reached depends upon the individual patient, his tolerance of the disease, and his individual circumstances and requirements. Until that point is reached, many patients gain benefit from an anticholinergic and/or amantadine.

Another issue may assume importance in the future, namely whether dopamine replacement therapy should be started with levodopa or with a directly-acting dopamine agonist. Whether the latter approach will provide longer and smoother benefit can only be resolved by comparative clinical trials which currently are being undertaken.

MANAGEMENT OF DRUG PROBLEMS

Gastrointestinal upset

Although peripherally-acting dopa decarboxylase inhibitors have markedly reduced the incidence of anorexia, nausea and vomiting provoked by levodopa, this still remains a major problem in a minority of patients. The new formulation of Sinemet (levodopa/carbidopa = 5/1 instead of 10/1) has helped to some extent, but neither this, nor the use of Madopar (levodopa/benserazide) has abolished the problem. Of course, such peripheral decarboxylase inhibitors have no effect on these symptoms when provoked by directly-acting dopamine agonists, such as bromocriptine or pergolide. A new approach to this problem has been the use, in Europe, of peripherally-acting dopamine antagonists, the best of which is domperidone.

Myocardial infarction

A common problem is what to do when a patient with Parkinson’s disease has a heart attack. Protection from the peripheral effects of levodopa and dopamine agonists is required after recent myocardial infarction, which predisposes to drug-induced cardiac dysrhythmias. The editors feel that it is safe to continue levodopa, provided that sufficient carbidopa (at least 100mg/day) is given at the same time. Likewise, domperidone can protect the heart against unwanted effects of dopamine agonists. In countries in which domperidone is not available, it may be more prudent to switch such patients to levodopa/carbidopa. Certainly, the editors believe it is more important to continue some form of dopamine replacement therapy in this situation than to stop it, which causes dramatic and distressing relapse of the parkinsonism.

Accidental sudden withdrawal of levodopa

In the editors’ experience, the sudden cessation of levodopa in a patient who has taken the drug for many years may cause a confusing akinetic ‘coma-vigil’ state, which can easily be reversed by reintroducing levodopa, if necessary, by nasogastric tube. Alternatively, where it is available, an intravenous injection of the water-soluble, fast-acting dopamine agonist, lisuride can be used.

Drug holidays

One of the ploys suggested in recent years to cope with some of the complications of chronic levodopa treatment has been the deliberate withdrawal of levodopa, a so-called ‘drug holiday’. The editors will not go into the rationale behind this approach, or into its theoretical implications for the controversy about the cause of loss of efficacy of levodopa therapy. However, they will comment on its practical value. The impression has grown that this is a useful approach for coping with violent fluctuations that may emerge during chronic levodopa treatment. In fact, the published descriptions of this technique referred mainly to its use in patients with loss of response and/or toxic side-effects of chronic levodopa therapy1,4. Stopping levodopa in such patients leads to disappearance of mental and dyskinetic complications, with return of the symptoms and signs of Parkinson’s disease. When levodopa is...