Hallucinations in Patients with Parkinsonism: Clinical Features and Management

David J Burn, MD, MA, FRCP, Consultant & Senior Lecturer in Neurology, Regional Neurosciences Centre, Newcastle General Hospital, Westgate Road Newcastle upon Tyne, UK.

Ian G McKeith, MD, FRCPsych, Professor of Old Age Psychiatry, Department of Old Age Psychiatry, Institute for Ageing and Health Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK.

Introduction
Parkinsonism is a common problem, particularly in the elderly. One percent of the population over the age of 65 has Parkinson's Disease (PD), rising to 2% over the age of 80. Parkinsonism is also a core feature of dementia with Lewy bodies (DLB), the second most common cause of neurodegenerative dementia, after Alzheimer disease (AD). To differentiate patients with PD who develop cognitive impairment from DLB, Consensus Criteria stipulate that parkinsonism must be present for 12 months or less for a patient with dementia to qualify for a diagnosis of DLB.¹ If the extrapyramidal features are present for longer than this before the dementia develops, the diagnosis is referred to as PD with dementia.

Although parkinsonism occurs in numerous other neurodegenerative diseases, including multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, as well as AD, hallucinations are less common.

Limb Apraxia: A Clinical Perspective

Deborah Hebert BSc(0T), MSc(Kin) PhD candidate, Ontario Institute for Studies in Education, Clinical Educator (OT), Toronto Rehabilitation Institute Clinical Associate, Department of Occupational Therapy, University of Toronto.

Eric Roy PhD, C Psy, Professor, Departments of Kinesiology and Psychology, University of Waterloo, Graduate Department of Rehabilitation Science University of Toronto, Toronto, ON.

When a person with neurological impairment engages in an unusual action such as pouring hot water into a cup with no tea bag and stirring it with a fork, or cutting bread with a knife oriented upside down and sideways, the impairment of limb apraxia should be suspected. Apraxia has been defined as, " a neurological disorder of learned purposive movement skill that is not explained by deficits of elemental motor or sensory systems".¹ While motor problems such as abnormal tone and posture, paresis, ataxia and dysmetria can coexist with limb apraxia,^2,3 this movement problem is one of conceptual understanding of action and/or production of movement.⁴ The deficit cannot be explained by intellectual deterioration, lack of cooperation, sensory disturbances, agnosia, disrupted body schema, visuospatial disturbances or aphasia.^3,5 There is evidence that aphasia and apraxia commonly co-occur, as they are predominantly found in right-handed clients with left hemisphere lesions; however, they are often clearly dissociated.

Parkinson’s Disease: An Update on Therapeutic Strategies

Daniel S Sa, MD and Robert Chen, MBBChir, MSc, FRCPC
Division of Neurology and Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON.

The treatment of Parkinson's Disease (PD) has undergone major changes over the past decade with the introduction of new drugs and the development of more advanced and reliable surgical procedures. However, the role of each of these different treatment alternatives is not yet clearly defined. Frequently raised questions include the most appropriate treatment in early PD and determining which patients with more advanced PD are suitable for surgery. In this review, we will attempt to address some of these issues.

Initial Treatment
The first decision to make is when to begin treatment. Since there is no therapeutic strategy proven to halt or slow disease progression, treatment initiation should be related to the level of disability. Therefore, drug therapy should be initiated when symptoms are interfering with social or occupational functions. This is usually due to impaired motor function but sometimes is related to embarrassment.

The next question is which treatment to offer. There is a long-standing debate regarding whether to start with levodopa or dopamine agonists. The levodopa proponents argue that it is still the most effective therapy for PD, and early treatment (before postural instability) has been proven to reduce mortality.

Canada: A Reputation for Excellence in Neurosciences

The neurosciences seem always to have been a strong point of Canadian medicine, from both a clinical and a research perspective. Montreal, with its Neurological Institute, has long been internationally renowned. In fact, the day I wrote this editorial, there was an article in the Globe & Mail announcing that a famous American neuroscientist was moving to the MNI because he felt there were greater opportunities there than in his current position in New York City! Clearly, Montreal remains at the forefront of neuroscience research, but it is no longer the only excellent Canadian venue. Several universities across the country have made neuroscience research a priority, and most have excellent multidisciplinary research enterprises. In my University (Toronto), there are numerous outstanding investigators. Don Stuss heads a group at the Baycrest Centre for Geriatric Care that has done groundbreaking work on frontal lobe function. Peter St George-Hyslop at the Centre for Research in Neurodegenerative Diseases (CRNDs), is an international authority on the genetics and molecular biology of Alzheimer disease. There is outstanding work being done on brain tumours, dementia, stroke, epilepsy and other neurological conditions.

However, in Canada there seems to be particular strength and depth in the field of movement disorders. Although we have one article from the United Kingdom (Hallucinations in Patients with Parkinsonism, by Dr. Burn and Professor McKeith), it is a relatively easy task to find Canadian experts in all facets of the movement disorders. One Canadian, Dr. Ali Rajput from Saskatoon, has made an incredible contribution by his careful clinical-pathological correlations in Parkinson's disease (PD). He is considered one of the world's leading clinicians in the care of patients with PD. He and Dr. Alex Rajput (his son) have written an article on how to differentiate Parkinsonian Dementia from Alzheimer disease, as well as on its management. We have an article on diagnosing and managing depression in Parkinson's disease by Dr. Mandar Jog, the director of the Movement Disorders Program at the University of British Columbia. Zhigao Huang and Robert Tsui from the Pacific Parkinson's Research Centre at UBC discuss COMT inhibition in Parkinson's disease. Robert Chen and Daniel Sa, from the University of Toronto, give an update on advances in therapeutic strategies for Parkinson's disease, including pallidotomy and deep brain stimulation.

Of course, Parkinson's Disease is not the only movement disorder. D'Arcy Little, a frequent contributor to this journal, discusses the epidemiology, presenting features, diagnosis and treatment of Huntington's Disease. In other articles, Deborah Hebert from the Toronto Rehabilitation Institute and the University of Toronto discusses limb apraxia from a clinical perspective. Dr. Madhuri Reddy has written an article on the natural history of long-term care clients. Dr. Robert Teasell from the University of Western Ontario, and one of Canada's leaders in stroke rehabilitation, shares his knowledge of the area with us. As well, the Regional Geriatric Programs of Ontario have submitted an educational module on Driving & Dementia. Enjoy!

Next month, by popular demand, the issue will focus on skin disorders in the elderly. Be sure not to miss it!

Asleep at the Wheel

Exactly how big a risk is it to drive if you are taking a dopamine agonist for Parkinson's disease? A survey by the Canadian Movement Disorders Group recently set out to answer this question. Somnolence is a recognized adverse effect of dopamine agonists, and two new dopamine agonists, pramipexole and ropinirole, have been reported to cause sudden-onset sleep spells in PD patients while they were driving. The group conducted a prospective survey of 638 consecutive, highly functional PD patients without dementia, 420 of whom were currently drivers. They assessed the sleepiness of the patients using a modified version of the Epworth Sleepiness Scale and the Inappropriate Sleep Composite Score. They found that patients taking a variety of different dopamine agonists had no differences in Epworth sleepiness scores, in the composite score or in the risk of falling asleep while driving. They also found that excessive daytime sleepiness is common although sudden-onset sleep is infrequent. The Epworth score had adequate sensitivity for predicting prior episodes of falling asleep while driving and its specificity could be increased by use of the Inappropriate Sleep Composite Score.

The authors recommend that patients should be educated to recognize the warning symptoms and the associated risks of these episodes occurring while driving and about the importance of never driving when sleepy.

Source

1. Hobson DE, Lang AE, Wayne Martin WR et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson Disease. A survey by the Canadian Movement Disorders Group. JAMA 2002;287:455-63.

Management of Dysarthria in Amyotrophic Lateral Sclerosis

Kathryn M. Yorkston, Ph.D., BC-NCD, Department of Rehabilitation Medicine, University of Washington, Seattle, WA.
David Beukelman, Ph.D., Department of Special Education and Communication Disorders, University of Nebraska, Lincoln, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska, Omaha, NE.
Laura Ball, Ph.D., Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska, Omaha, NE.

Summary
This article describes intervention for dysarthria associated with amyotrophic lateral sclerosis (ALS). Five critical periods are presented including a stage with normal speech, detectable speech disturbance, behavioural intervention, use of augmentative communication, and loss of useful speech. Intervention strategies at each of these stages are outlined with the goal of maintaining functional communication regardless of the severity of dysarthria.

ALS is a rapidly progressive degenerative disease of unknown etiology involving the motor neurons of both the brain and spinal cord.¹ The symptoms characteristic of ALS are generally classified by site of involvement (that is, upper motor neuron versus lower motor neuron) and by whether spinal nerves (those innervating the arms and legs) or bulbar nerves (those innervating the muscles of speech and swallowing) are involved.

Parkinson’s Disease and Parkinsonism in the Elderly

Editors: Jolyon Meara and William C. Koller
Cambridge University Press, 2000
ISBN 0 521 62884 9

Reviewed by Barry Goldlist, MD, FRCPC, FACP

This text is a collaboration between chapter authors and editors from the United Kingdom and the United States.

Of late, there has been an explosion of knowledge and literature in the broad field of movement disorders, so to stand out from this field, the text would have to be well written and truly focus on the elderly. Many texts simply state "condition X" is common in the elderly, and then present a discussion that could have been lifted from any general textbook.

This book is certainly well written. The first chapter gives a glossary of terms that is helpful, particularly for a non-neurologist. The second chapter, on the diagnosis of parkinsonism in the elderly by Professor Rodnitzky, is extremely well written. The chapter is organized in a way that follows normal clinical reasoning, and although concise, contains more than enough information for a generalist physician. Reading this chapter made me feel I was in the company of a master clinician. The third chapter is also very good. Although the neuropathological basis of PD is not age-specific, the chapter discusses specific geriatric issues such as comorbidity, clinical heterogeneity, age-related pattern of disease presentation and the nature of a comprehensive geriatric assessment as it relates to patients with PD. Specific problems related to the elderly are also stressed. There are individual chapters on essential tremor, gait apraxia and epidemiology, and there has been a concerted effort to focus on the elderly. The relatively minimal amount of repetition in the chapters is further evidence of high quality editing.

The numerous chapters on the role of rehabilitation professionals in the care of elderly PD patients really distinguishes this book from a more general text, and might make this text suitable for general neurologists who want specific details about handling older PD patients. It is certainly of value for generalists and geriatricians who manage elderly patients with PD. It is also probably of interest and value to rehabilitation professionals who work with PD patients.

Another Gene Identified for Amyotrophic Lateral Sclerosis

A team of researchers studying highly inbred families in Kuwait, Tunisia and Saudi Arabia has identified a new gene for an inherited form of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Although only 5-10% of cases of ALS are hereditary, the findings may explain the mechanisms that underlie the disease.

ALS2 is an autosomal recessive form of juvenile ALS and has been mapped to chromosome 2q33. The researchers reported two independent deletion mutations linked to ALS2 in the coding region of a new gene, ALS2. The deletion mutations lead to frameshifts that generate premature stop codons. The gene is expressed in various tissues and cells, including neurons throughout the brain and spinal cord, and encodes a protein that is suggested to be a putative GTPase regulator. Deletion mutations that are predicted to cause a loss of protein function provide strong evidence that ALS2 is the causative gene underlying this form of the disease.

It is hoped that if the gene controls a protein that is necessary for cell survival, this could help in the development of drugs to protect these neurons in ALS, and possibly in other forms of neurodegenerative diseases.

Source

1. Hadano S, Hand CK, Osuga H, et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nature Genetics 2001;29:166-173.

Stem Cell Transplants Fail to Cure Parkinson’s disease

A controversial study on the treatment of Parkinson's disease (PD) has come to a disappointing end. Previous open clinical trials had suggested that transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease was beneficial. However, a recent study published in the New England Journal of Medicine has found that in a controlled trial, no significant improvement was noted in patients with transplanted neurons. Freed et al. transplanted precursors of dopaminergic cells in fragments of mesencephalon isolated from human fetuses into the brains of patients with PD. Twenty patients received the operation, in which four holes were drilled in their skulls, and twenty others underwent sham surgery, in which the drill did not go all the way through the skull. Encouragingly, some of the implanted cells were found to have survived and differentiated on histologic examination or positron-emission tomography (PET). However, there was no correlation between these findings and motor improvements in the patients. No significant improvement was noted in elderly patients who had undergone the transplantation. However, younger patients, who make up about 40% of Parkinson's patients, showed a slight improvement of symptoms, but this only lasted for one year after the surgery.

The study had generated considerable controversy, as many people felt that it was unethical to perform sham operations in patients because of the pain and the risk of complications associated with the surgery.

Source

1. Freed et al. New England Journal of Medicine. 2001; 344:710-719.

Steering Through Murky Ethical Waters

Is it Ethical to Use Foetal Tissue for the Treatment of PD?

David Kaplan, MSc(HA)
Joint Centre for Bioethics
Faculty of Medicine,
University of Toronto

Surgical transplantation of foetal brain cells has been reported to substantially improve the symptoms associated with Parkinson's Disease. Parkinson's disease, which is characterized by tremors, muscular rigidity, and akinesia, is believed to result from the deterioration of the brain's dopamine producing cells in the substantia nigra (the neural centre for the initiation and control of movement). This disease afflicts 70,000 Canadians, and unfortunately, approximately ten percent of these patients are refractory to conventional medical therapy. Clearly, new methods to control the disease would be of substantial benefit to these patients. In 1995, the Canadian government introduced legislation that would have made it difficult, if not illegal, to conduct research into foetal tissue transplant. Although this Bill died on the parliamentary order desk, there remains the prospect of reintroducing such legislation. The purpose of this article is to examine the murky ethical waters that surround the topic of research and therapy involving foetal tissue. However, I will not attempt to validate the merits of this therapy in this brief analysis.

Procurement
Obviously, a source of foetal tissue is required, in order to perform foetal tissue transplantation surgery. There are three potential sources for this tissue.