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Catechol-O-methyltransferase Inhibition in Treatment of Parkinson’s Disease

Catechol-O-methyltransferase Inhibition in Treatment of Parkinson’s Disease

Teaser: 

Zhigao Huang, MD, PhD, Clinical Fellow,
Ajit Kumar, DM, Clinical Fellow,
Joseph Tsui, MD, FRCPC, Professor, Department of Medicine, University of British Columbia, Vancouver, BC.

Introduction
Long-term treatment with dopaminomimetic drugs is often complicated by the occurrence of motor complications in Parkinson's Disease (PD) patients. This is especially true with levodopa, which remains to date the mainstay of treatment of PD. These motor complications consist of fluctuations and dyskinesias. Fluctuations refer to predictable or unpredictable changes of motor response that occur in relation to levodopa administration. Dyskinesias refer to abnormal excessive movements. Motor fluctuations can affect up to 50% of PD patients after five years of levodopa treatment.1 The main categories of fluctuations are 'wearing-off' and 'on-off.' Clinically, 'wearing-off' is characterized by a shortened duration of motor response and a rapidly waning effect in response to each oral dose of levodopa. 'On-off' refers to random fluctuations in motor response seemingly unrelated to levodopa administration.2

In early PD, the motor response to levodopa administration lasts longer than would be inferred from the plasma half-life of levodopa. Presumably, this phenomenon is related to surviving nigrostriatal neurons being able to store dopamine (DA) synthesized from exogenous levodopa, thus serving a buffer-like function.

Hallucinations in Patients with Parkinsonism: Clinical Features and Management

Hallucinations in Patients with Parkinsonism: Clinical Features and Management

Teaser: 

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

Limb Apraxia: A Clinical Perspective

Teaser: 

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

Parkinson’s Disease: An Update on Therapeutic Strategies

Teaser: 

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.

The Biological and Cognitive Effects of Estrogen on the Aging Brain

The Biological and Cognitive Effects of Estrogen on the Aging Brain

Teaser: 

Elise J. Levinoff, BSc1,2, Howard Chertkow, MD, FRCPC1,2,3
1Bloomfield Centre for Studies in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University
2Department of Neurology and Neurosurgery, McGill University
3Division of Geriatric Medicine, Dept. of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, PQ.

Alzheimer disease (AD) is a neurodegenerative disease of elderly patients, pathologically characterized by the presence of senile plaques and neurofibrillary tangles in the brain. This pathology occurs in the cerebral cortex, specifically within the temporal lobes, resulting in impairment in cognitive domains such as short-term memory, attention, semantics, as well as aphasia and apraxia.1 Patients also show marked changes in behaviour and are impaired in activities of daily living (ADLs). The causes of AD are unknown, but age is a major risk factor. Women are at a higher risk of developing AD, although this may be due, in part, to increased longevity. Additionally, mechanisms of neuronal injury, such as the presence of cerebral infarcts and consequences of head trauma, increase the risk of developing AD. Expression of the APOE-e4 genotype has also been associated with an increase in the risk of developing AD.1

Presently, there is no cure for AD.

Cognitive and Behavioural Disturbances in Parkinson’s disease

Cognitive and Behavioural Disturbances in Parkinson’s disease

Teaser: 

Taresa Stefurak MSc, MD, FRCPC, Neuropsychiatry Fellow, Rotman Research Institute, Baycrest Centre for Geriatric Care, University Health Network, Department of Neurology, University of Toronto, Toronto, ON.

Introduction
Although Parkinson's disease (PD) is by definition a movement disorder, with a clinical diagnosis made by the presence of two out of three cardinal levodopa-responsive motor signs (tremor, rigidity, bradykinesia), both cognitive and neuropsychiatric symptoms are also important components. The clinical impact of these neurobehavioural symptoms is supported by a study in which the strongest predictor of quality of life perceived by PD patients was the presence of depression.1 Cognitive impairment as well as postural instability and disability also contributed to poor quality of life. Behavioural disturbances and dementia are the primary reasons for nursing home placement in PD patients.2

Characterizing the nature of these symptoms in PD provides an important model to understand the underlying mechanisms of disease progression and brain function. Although psychosocial aspects may play a role in some of the behavioural and mood disturbances in PD, evidence suggests that the underlying mechanism for these symptoms arises from the biological dysfunction of anatomical and neurochemical substrates that occur in PD.

Cardiac Tumours: Presentation and Treatment

Cardiac Tumours: Presentation and Treatment

Teaser: 

Nimesh D. Desai1, MD, Jagdish W . Butany, MBBS MS, FRCPC2
Departments of Cardiac Surgery
1 and Pathology2, Toronto General Hospital / University Health Network and University of Toronto, Toronto, ON.

Introduction
Cardiac tumours are uncommon,when compared to other tumours. A few of these are more frequently seen in the young (first and second decade of life),while most are more common in older individuals ( fourth decade of life and later). When they occur they are more likely to be metastatic than primary cardiac neoplasms, the latter more likely benign than malignant, and the former more common in older individuals.Their manifestations are varied and invariably pose a diagnostic challenge. The first pre-mortem diagnosis of an intracardiac myxoma was not made until 1952, using angiography.1 Today, the accurate clinical diagnosis of cardiac tumours is made with non-invasive techniques such as echocardiography.

Incidence
Autopsy studies have shown an incidence of between 0.0017 and 0.3 percent for primary cardiac tumours.2,3 In adults the mean age at diagnosis of tumours is: sarcoma 40 years; myxoma 50 years; mesothelioma, 57 years; papillary fibroelastoma, 59 years; and lipomatous hypertrophy, 64 years.4 The incidence of secondary or metastatic cardiac tumours is significantly greater than that of primary tumours and is approximately 1.23%.

Clinical Approaches to Male Breast Cancer

Clinical Approaches to Male Breast Cancer

Teaser: 

Stefan Glück1,2 MD, PhD and Christine Friedenreich3 PhD
1Professor, Dept. Oncology, Medicine and Pharmacology & Therapeutics Faculty of Medicine, University of Calgary, Calgary, AB.
2Senior Leader, Clinical Research Program Medical Oncologist, Tom Baker Cancer Centre, Calgary, AB.
3Research Scientist, Division of Epidemiology, Prevention and Screening, Alberta Cancer Board, Calgary, AB.

Introduction
In 1996, the most recent year for which complete statistics for Canadian cancer incidence are available, a total of 118 new cases of breast cancer were diagnosed in men.1 This incidence rate is approximately 0.7% of the 16,551 cases diagnosed in women.1 This proportion of male to female breast cancers is typical of western populations, although exceptionally high proportions of male to female breast cancers have been found in countries such as Egypt and Zambia, with studies reporting 6% and 15%, respectively.2,3

In many aspects, the disease has a similar clinical course in both genders. However, because male breast cancer is so rare, it has been very difficult to accumulate knowledge through research, especially through large prospective trials. Many aspects of the diagnosis and treatment of male breast cancer remain controversial and even in the future, clinical research will be difficult.

Screening for Colorectal Cancer in Older Adults

Screening for Colorectal Cancer in Older Adults

Teaser: 

Peter G. Rossos MD, FRCP(C)
Elaine Yeung MD

Division of Gastroenterology, University Health Network
University of Toronto, Toronto, ON.

Introduction
Colorectal cancer (CRC) is the third most common cause of cancer and second leading cause of cancer death in Canada. It is estimated that there were 17,200 new cases and 6,400 deaths from colorectal cancer in Canada in 2001. When both women and men are considered together, colorectal cancer is the second most frequent cause of death from cancer among Canadians.1 Most CRC occurs in average risk individuals for whom there are no accepted guidelines for screening.2 Higher risk categories include those who have a family history of CRC, a personal history of CRC, colonic adenomas or inflammatory bowel disease, and the familial syndromes including familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC).3 This discussion will focus on average risk older adults, who comprise almost all CRC cases in patients 65 years of age or older.

Epidemiologic Considerations
Although age-standardized incidence and mortality rates have been declining for CRC since 1985, the number of new cases has continued to rise steadily and significantly among both men and women as a result of the growth and aging of the population. Recent data from the National Cancer Institute of Canada is displayed in Figures 1 and 2.

Ovarian Cancer in Older Women: Management and Treatment Options

Ovarian Cancer in Older Women: Management and Treatment Options

Teaser: 

Natalie S. Gould MD, Fellow and Clinical Instructor
D. Scott McMeekin MD, Assistant Professor Section of Gynecologic Oncology,
Department of Obstetrics and Gynecology
University of Oklahoma Medical Center, Oklahoma City, OK, USA.

Ovarian cancer is a disease of older women, with 48% over the age of 65 at diagnosis.1 It is also the most deadly of gynecologic malignancies, accounting for more deaths than cervical and endometrial carcinoma combined in the US. An estimated 23,400 new cases of ovarian cancer will be diagnosed in 2001 with 13,900 deaths in the US.2 As our population ages, the number of women affected by ovarian cancer will increase. Cancer limited to an ovary is typically silent and discovered incidentally on exam or at surgical exploration for other reasons. Patients with disease that has spread beyond the ovaries may present with vague gastrointestinal symptoms, bloating, diarrhea, pain and changes in bowel or bladder habits. On physical exam, patients will have a pelvic mass and often ascites. Due to the absence of symptoms until the malignancy has spread beyond the ovaries, and the lack of good screening tests, approximately 70% of patients present with advanced disease and overall survival is poor.3 (Table 1).

Initial management involves cytoreductive surgery aimed at removal of the greatest volume of tumour (Table 2).