Preface

Movement disorders are a group of neurological disorders often without an identifiable etiology or manifestations of genetic or neurodegenerative disorders. Classical examples include idiopathic Parkinson’s disease, essential tremor, various forms of dystonia, chorea, myoclonus, tics, and other hypokinetic and hyperkinetic movement disorders. These and other movement disorders may also occur as presenting or prominent features of general neurological disorders such as stroke, encephalitis, multiple sclerosis, or CNS tumors. Moreover, they may also occur in the setting of a wide spectrum of systemic diseases, including metabolic and endocrine disorders, intoxications, hematological diseases, cancer, or infection. These latter situations where movement disorders are the hallmark of general neurologic or systemic conditions is when clinicians may face challenges of diagnosis and treatment. Affected patients may present to the internists and other physicians, including neurologists not skilled in movement disorders, who may be unfamiliar with the phenomenology or differential diagnosis.

We have invited an eminent group of international experts to contribute to this textbook, which we hope will serve as a reference guide to both neurologists and non-neurologists, residents, and consultant specialists who encounter patients with movement disorders in the setting of systemic or general neurological conditions. Following an introductory section summarizing the principles of the clinical approach to correctly classify movement disorder syndromes, their underlying pathophysiology, and their management, the different chapters provide comprehensive information on the clinical features, prevalence, pathophysiology, and diagnostic and management approach to specific classes of systemic or general neurologic conditions, where affected patients may present with movement disorders. We have also included a section addressing the important field of systemic complications occurring in the setting of primary movement disorder syndromes, including problems of swallowing, gastrointestinal dysfunction, orthostatic hypotension, and other types of autonomic failure, as well as movement disorder emergencies.

Introduction

Almost every infectious agent has the theoretical capacity to invade brain tissue as long as it manages to penetrate the blood-brain barrier. This might occur during viremia or bacteremia by active transmigration through the blood-brain barrier or via direct access to the CSF space in conditions of CSF leakage following, for example, neurosurgical procedures or open traumatic brain injury. While meningitis usually does not affect brain tissue – unless there is concomitant meningovasculitis which may give rise to ischemic strokes – the neurological syndromes of encephalitis are to a large part determined by potential anatomical predilection for sites of brain involvement of the different causative pathogens.

This chapter deals with encephalitides of various origin in which movement disorders have been described either as typical hallmarks or as potential or even rare manifestations of CNS inflammation. It will not deal with paraneoplastic encephalitides or involvement of the brain in autoimmune diseases (see Chapters 5 and 6). Neither will it deal with movement disorders in systemic infection, in particular, not with movement disorders in HIV infection (see Chapters 7 and 8).

Introduction

Over the past few decades neurology has become a field not only of refined and ever-more precise diagnostics, but has also seen a tremendous growth of its therapeutic armentarium. Movement disorders are a paradigmatic example of this development, with Parkinson’s disease being the first neurodegenerative disease – and still the only one – for which pharmacological substitution of an underlying neurotransmitter defect is able to largely abolish symptoms in the majority of patients for extended periods of time. Effective drug therapies are also available for a variety of other movement disorders, including tremor, chorea, dystonia, tics, or myoclonus. Management of movement disorders, however, goes far beyond medical therapy and includes non-pharmacological measures such as exercise and physical therapies, retraining programmes, biofeedback strategies, as well as occupational and speech therapies. More recently, local chemodenervation of selected muscles using targeted botulinum toxin injections has provided a highly successful new treatment modality for a variety of hyperkinetic focal disorders. Furthermore, functional stereotactic neurosurgery can provide dramatic benefit even in instances of severely disabling drug refractory movement disorder conditions including Parkinson’s disease, essential tremor disorders, and dystonia.

Most, if not all, evidence for efficacy of these different approaches has come from clinical trials in selected, homogeneous populations of subjects with degenerative or idiopathic varieties of the different movement disorder syndromes. There is much less formal evidence to guide treatment decisions in those patients in whom movement disorders appear in the context of systemic diseases or as part of the symptomatic spectrum of general neurological conditions. Managing patients with these types of disorders is, of course, first guided by treatment and – if possible – cure of the underlying condition. In many instances this will not be possible or movement disorders may persist as a sequel of the primary condition. Secondly, symptomatic therapies of the movement disorders must be built on correct phenomenology and classification of the type of movement disorder present or identification of the most relevant disturbance in the setting of mixed movement disorders. Selected treatments will then frequently be those that have been shown to be effective in idiopathic varieties of the same disorder. Thirdly, the management approach will often have to be multimodal, combining non-pharmacological, pharmacological and, less often, neurosurgical approaches, and multidisciplinary, involving not only the primary care physician and a neurologist, but also allied health professionals, including specially trained nurses, psychologists, and physical, occupational, and speech therapists.

Introduction

Stroke is the second leading cause of death in industrialized nations and the most important cause of permanent neurological disability in the elderly. According to recent WHO estimates, stroke ranks second after dementia in the overall burden of disease from brain disorders and accounts for about 4.1 percent of all cause burden of disease (Murray et al. 2012). Prevalence of stroke rises with advancing age and beyond the age of 70 annual stroke incidence rises to above 2,000 per 100,000 (Diaz-Guzman et al. 2012; Kissela et al. 2012; Khellaf et al. 2010; Warlow et al. 2003). Approximately 85 percent of all strokes are ischemic in nature, while 15 percent result from intracerebral hemorrhage. Arteriosclerosis is the single most important cause of ischemic stroke, either via large or small vessel disease or combinations followed by embolic stroke from cardiac sources. Stroke symptoms depend on the anatomic location of brain infarcts or hemorrhages and the functional connectivity of lesion sites. Involvement of the basal ganglia and their afferent and efferent connections is very common in strokes affecting the middle cerebral artery territory, and yet movement disorders seem to be relatively rarely reported in the context of stroke. This may be partially due to observer bias with focus on acute stroke symptoms and acute management, while in many cases movement disorders only develop after acute stroke symptoms have resolved. Also, the distinction between vascular “look-alikes” of common degenerative movement disorders and their bona fide counterparts can be challenging, as probably best exemplified by the controversies and uncertainties related to vascular parkinsonism.

Mechanisms underlying stroke-related movement disorders

Dysfunctional sensorimotor integration is the common final pathophysiological pathway for all movement disorders and the neural networks involved include motor loops interconnecting the cerebellum, brainstem nuclei, basal ganglia, thalamus, and motor and pre-motor cortical areas (Abbruzzese and Berardelli 2003).