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Book Reviews   |    
Mental and Behavioral Dysfunction in Movement Disorders
Reviewed by Mark Groves, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2004;16:539-542. doi:10.1176/appi.neuropsych.16.4.539
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Edited by Marc-André Bédard, Yves Agid, Sylvain Chouinard, Stanley Fahn, Amos Korczyn and Paul Lespérance, Published 2003, Humana Press, Inc., Totowa, NJ, 561 pages, ISBN#1-58829-119-7, price: $185

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Historically, the basal ganglia were thought to primarily be important to motor function. Research studies over the past two decades in the areas of psychiatric disorders and movement disorders, however, have yielded converging findings implicating the critical roles of frontal-subcortical circuits and the basal ganglia in the cognitive, affective and motor symptoms of psychiatric and neurological disorders. While the cognitive and affective symptoms of some movement disorders such as Huntington's disease have long been recognized, such symptoms have often been underrecognized by neurologists in other movement disorders such as Parkinson's disease (PD). Likewise, some psychiatric researchers are increasingly recognizing the relevance of the full triad of neuropsychiatric symptoms (cognitive, emotional, and motor symptoms) to psychiatric disorders such as depression. As a result of converging research findings in psychiatry and the neurology of movement disorders, there has been an explosion of interest in the cognitive and affective symptoms of movement disorders. This book concretely represents this increased interest and serves as an excellent review and comprehensive update of the results of research in the cognitive and affective aspects of movement disorders.

This edited volume originated, in part, from a recent conference sponsored by the Movement Disorder Society in Montreal and includes contributions from over 90 experts in the field. Its forty chapters are organized into seven sections. This book will be of great interest to both clinicians and researchers in movement disorders and neuropsychiatry. All chapters review literature relevant to the subject, but some chapters are more clinically focused, others more research based. In its entirety, this book serves as a terrific comprehensive update and review, but many readers will prefer reading a selection of chapters relevant to their own clinical work or research. The organization of the book into well-defined subsections, its extensive chapter bibliographies, and the thorough indexing make selective reading possible and allow the book to serve as a well-needed reference in the neuropsychiatry of movement disorders.

The book's introductory section focuses on historical issues in the study of behavioral dysfunction in movement disorders. The introductory chapter provides a concise and fascinating review of early references (or lack thereof) to behavioral and cognitive aspects of Parkinson's disease and Huntington's disease. James Parkinson's original 1817 Essay on the Shaking Palsy concluded "senses and intellect are uninjured." The author, Christopher Goetz, traces this bias through subsequent decades, and describes Charcot's (and others') opposing viewpoints. The chapter's historical review of literature on Huntington's disease is equally engaging.

Section II comprises four overview chapters reviewing the evidence for the basal ganglia and cerebellum's importance to cognitive and affective functions. Frank Middleton offers a concise review of the anatomy of the basal ganglia and frontal-subcortical circuits, and then systemically reviews physiological studies, functional imaging studies, pathological research and molecular research supporting the basal ganglia's influences on cognition. Suzanne Haber emphasizes two mechanisms by which "cross-talk" between parallel frontal-subcortical circuits can occur. 1.) She proposes a "hierarchy" of frontal-subcortical circuits from prefrontal to premotor to motor, linked through "an ascending midbrain spiral" of pathways between the anatomically separate striatal terminals of these parallel frontal-subcortical circuits and their overlapping projections to midbrain dopaminergic cells. Multiple diagrams effectively illustrate this complex but important model. 2.) She then discusses corticothalamic projections (often overlooked in models of basal ganglia function) which can be divided into reciprocal and nonreciprocal components. Haber proposes that the nonreciprocal corticothalamic projections are derived from more rostral cortical areas such that the flow of information from cortex to thalamus is from limbic and cognitive areas into premotor and motor regions of thalamus. This results in "an integrated feedforward processing." Haber suggests that these two anatomical mechanisms for "cross-talk" between distinct frontal-subcortical circuits enable the basal ganglia and cortex to effectively coordinate motivational, cognitive and motor elements of behavioral responses. Jeremy Schmahmann reviews evidence for the role of the cerebellum in cognition and emotion, emphasizing that it is not simply involved in motor control. He describes the anatomical organization of connections between the cerebellum and cortex and discusses the characteristics of the "cerebellar cognitive affective syndrome that emerges from damage to the cerebellum."

Sections III and IV focus on cognitive deficits observed in movement disorders. Julie Stout and Jane Paulsen offer a clear and concise overview of neuropsychological assessment of movement disorder patients. They describe common reasons for referrals, and make a number of specific recommendations about how to adapt neuropsychological tests to the particular needs and limitations of movement disorder patients. Other chapters focus on apathy, cognitive control, speech and language, and apraxia. Two chapters describe primate models of Huntington's disease and Parkinson's disease and the experimental induction and reversal of cognitive deficits in these animal models. Certainly, such animal models offer exciting opportunities to evaluate new potential treatments and learn more about these devastating diseases.

Marc-André Bédard and colleagues review the evidence for nondopaminergic influences on cognition in Parkinson's Disease. They emphasize that dopaminergic dysfunction cannot alone explain the cognitive dysfunction observed in PD patients (described by them as the "subcorticofrontal syndrome"—to be distinguished from dementia of the Alzheimer type or Lewy Body dementia) since many cognitive deficits are not reversed by dopaminergic medication. They discuss in particular the role of acetylcholine and review the evidence for the benefits to PD patients of treatment with cholinesterase inhibitors. While many have hesitated to use these agents in PD patients due to theoretical concerns that they might exacerbate the motor symptoms of PD, Bédard and colleagues note that recent studies of donepezil and rivastigmine have not been shown to worsen motor symptoms. Further research is needed to explore the utility of these agents in treating the "subcorticofrontal syndrome."

Jean Saint-Cyr offers an excellent review of the cognitive consequences of three neurosurgical interventions for Parkinson's disease: posteroventral pallidotomy, deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi), and DBS of the subthalamic nucleus (STN). He concludes that accurate positioning of either lesions or DBS is critical in minimizing risks of worsened cognitive function postoperatively and maximizing the benefits to motor function. Deep brain stimulation is certainly an exciting new treatment for Parkinson's disease, but can precipitate cognitive and emotional changes. As techniques are improved, and further research is conducted, it seems likely that DBS will experimentally be tried for a number of treatment-refractory psychiatric disorders.

Section V focuses on dementia in movement disorders. Andrew Kertesz offers an overview of the spectrum of dementia in movement disorders, emphasizing areas of considerable overlap between diagnostic groups such as the spectrum of Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. The two chapters that follow focus on the neuropathology and genetics of the two major classes of neurodegenerative disorders that lead to dementia: the synucleinopathies (deposition of Lewy bodies) and the tauopathies (deposition of tangles). Kurt Jellinger reviews the comparative neuropathology of various neurodegenerative disorders and highlights areas of controversy and overlap in pathological features of these conditions. John Hardy offers a synthesized model for the pathogenesis of these two classes of disorders.

Gilberto Levy and Karen Marder's chapter on the prevalence, incidence, and risk factors for dementia in Parkinson's disease is exceptionally well organized and clear. Levy and Marder review the literature on the prevalence of dementia in PD and highlight some of the limitations of previous studies (inaccurate diagnoses, variable criteria for dementia, and different patient populations) that account for the wide range of estimates of prevalence in the literature. Additionally, they systematically review the literature on risk factors for dementia in PD. A summary chart of risk factors outlines the demographic, clinical, neuropsychological, genetic, and environmental factors that have been reported to increase risk of dementia in PD. Of these factors, they stress that only age and severity of extrapyramidal signs have consistently been reported as risk factors for dementia in multiple studies.

The characteristic neuropsychiatric symptoms and treatment of patients within the dementia with Lewy bodies-Parkinson's disease dementia spectrum are reviewed by Clive Ballard and Alan Thomas. The following chapter by Elaine Perry and colleagues emphasize the role of cholinesterase inhibitors (ChEIs) in the treatment of the neuropsychiatric symptoms of DLB. Amos Korczyn and Nir Giladi conclude in their chapter that ChEIs may be useful for the treatment of dementia in PD as well.

Section VI focuses on the neuropsychiatric aspects of movement disorders. Neuropsychiatric clinicians will find the 13 chapters in this section particularly useful and high-yield. Edward Lauterbach reviews the anatomical and clinical evidence for the role of the globus pallidus in mood disorders. Taresa Stefurak and Helen Mayberg's elegant, comprehensive and well-organized chapter on cortico-limbic-striatal dysfunction in depression is a highlight of this book. Stefurak and Mayberg justify their use of PD as a model system for studying the role of striatal pathways in affective syndromes. They compare the cognitive and psychomotor symptoms of melancholic depression with parallel symptoms in PD, and emphasize that no single neurotransmitter defect can fully explain the spectrum of symptoms in either primary depression or PD depression. Functional imaging studies (resting state studies and treatment studies) of primary affective disorder patients and PD patients with depression are compared, and a working model of the neurocircuitry of depression is proposed based on research to date.

Irene Litvan and Jaime Kulisevsky illustrate the parallels between hypokinetic and hyperkinetic motor symptoms and the hypoactive (apathy) and hyperactive (agitation) neuropsychiatric symptoms that frequently accompany the motor symptoms. the literature supports their hypotheses: 1) agitation in hyperkinetic disorders such as Huntington's disease is due to an excitatory subcortical output through the medial and orbitofrontal cortical circuits; and, 2) apathy in hypokinetic disorders such as Progressive supranuclear palsy is due to hypostimulation of the medial frontal circuit.

Vladimir Kostic and colleagues offer an excellent review of the diagnosis and treatment of depression in Parkinson's disease. They comprehensively cover prevalence, diagnosis, and treatment of depression in PD, concluding from their review of the literature that "there are no established first-choice antidepressant drugs for patients with PD." The next chapter covers the diagnosis and treatment of psychotic symptoms in PD. Dag Aarsland and Jan Petter Larsen include useful tables on differential diagnosis, and outline general principles of treatment. Additionally, a treatment algorithm of psychotic symptoms is provided, and another useful table reviews case studies of atypical antipsychotics in PD. The table focuses on whether or not psychotic symptoms improved in the study patients, and whether or not the parkinsonism worsened on the antipsychotic agents.

Rapid eye movement sleep behavior disorder (RBD) is reviewed and its relationship to PD, DLB and Multiple System Atrophy (MSA) is emphasized. Clinical features of this fascinating parasomnia are reviewed, and treatment is discussed. Bradley Boeve and colleagues conclude in this chapter that RBD may be an early clinical manifestation of MSA, PD and DLB as it often precedes the onset of cognitive and motor symptoms in these neurodegenerative disorders and is strongly associated with these disorders.

Daniel Sa and Anthony Lang review the diagnostic and treatment challenges of psychogenic movement disorders. They discuss a number of features suggestive of psychogenic dystonia but emphasize a number of caveats for these generalizations. Two chapters focus on the neuropsychiatric symptoms of Huntington's disease. Mark Guttman and colleagues discuss the treatment of psychotic and mood disorders in Huntington’s disease (HD) offering useful consensus statements on treatment of these symptoms since rigorous clinical trials are not generally available to guide treatment decisions. Adam Rosenblatt and colleagues discuss the treatment of aggression, irritability, apathy and other frontal lobe symptoms seen in HD patients. Together, these two excellent chapters provide an up-to-date review of the psychiatric management of this fascinating, but devastating disease. Remaining chapters in this section cover Tourette syndrome, obsessive compulsive disorder (OCD) and "spontaneous dyskinesias" (dyskinesias observed in patients with schizophrenia who have never been exposed to dopamine receptor blocking agents.)

The final section of this volume focuses on quality of life (QOL) in Parkinson's disease. Anette Schrag and Caroline Selai review the medical and psychosocial determinants of QOL in PD. Numerous studies and their findings are summarized in a helpful table. A consistent finding of many of these studies was that depression was often the most important factor associated with poor health-related QOL. Given the treatability of depression in PD and these research findings, this research emphasizes the importance of increased recognition and treatment of depression in PD patients! Other factors associated with QOL in PD are reviewed. Schrag and Selai conclude that "it is not disease severity and presence of symptoms that primarily determines patients' QOL, but the disability associated with these symptoms and the emotional response to them." Remaining chapters in this important section cover issues of sexuality in PD, daytime sleepiness and sleep attacks, and life expectancy.

Overall, I strongly recommend this book to researchers and clinicians working with movement disorder patients as well as others interested in neuropsychiatry.

Dr. Mark Groves is Attending Psychiatrist in Movement Disorders at the Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY

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