IS151 Use and misuse of antiparkinson medications

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Invited Speaker Abstracts

Wednesday, November 9, 2005

muscle fibers that contain amyloid deposits. Electron microscopy reveals an accumulation of cytoplasmic and intranuclear 15- to 21-nm tubofilments. The inflanmmto ry response consists of macrophages and CD8 + cytotoxic/suppressor T lymphocytes and is often the most prominent initial lfistologic finding. Despite the inflammatory response in IBM, the disease is typically refractory to immunosuppressive therapy. This lack of response to immunosuppressive treatment distinguishes IBM from dermatomyositis, and polymyositis. When IBM patients are placed on prednisone therapy, strength continues to deteriorate despite a decrease in serum creatine kinase levels and the suppression of infianmmtion on repeat muscle biopsy. In addition, although inflammation decreases, the number of fibers with vacuoles and amyloid deposits increases over time. The addition of other immunosuppressive drugs does not improve the poor therapeutic response. These observations suggest that IBM is a degenerative rather than an autoinmmne inflanmmtory myopathy and that the inflanmmtion may be a secondary response. IS150 Clinical Assessment and Recognition of Sub-Types of Parkinson Disease

Fahn, S. Columbia University, New York, N); U.S.A Clinical severity of ParkJnson disease (PD) can be assessed by different rating scales. The most comprehensive is the Unified Parkinson's Disease Rating Scale (UPDRS). It is widely used in current clinical trials, and it is also highly useful in routine clinical practice to follow disease progression and response to therapy. The UPDRS assesses behavioral, activities o f daily living and motor features of tremor, bradykinesia, rigidity, posture, postural reflexes and freezing of gait. A fourth part of the UPDRS also provides an assessnlent of dyskinesias and motor fluctuations. A newer version of the UPDRS is in preparation. The Hoehn & Yahr Staging system provides a cruder estimate of severity, ranging from Stage I (unilateral) to Stage V (wheel-chair bound). The Schwab-England Activities of Daily Living (ADL) Scale provides a number from 10% to 100% o f n o m l a l ADL; it's advantage is that the number can be provided by the patient/fanfily and, with it's single number result, places the patient on a performance spectrum that can be easily recognized as severity of the disease. All three scales can provide scores when the patient is "on" and when "off." In addition to the above three global scales, there are scales that measure specific features of PD. For example, there are scales that assess levodopa-induced dyskinesias, and scales to quantify depression, fatigue and other aspects o f PD. There are several ways to sub-type PD, each having its own value. Examples include: age (young-onset, older onset.); tremor (present, not present, tremor-predominant, postural instability gait disorder predominant); familial vs. sporadic. Age is a factor in the development of motor complications. The non-tremulous fotln expands the differential diagnosis to include the Parkinson-Phis syndromes. The presence of tremor may impact a slower rate o f progression. IS151 Use and Misuse of Anfiparldnson Medications John Nutt Evidence-based medication provides information about efficacy of antiparkinson medications and offers guidelines for their use in a few specific situations. As a consequence clinicians make most treatment decisions based on their experience and scientific prejudice. Using my experience and interpretation of the literature, I suggest several alternatives to conventional approaches to treatment. 1. Let the major determinants of quality of life, depression, mobility and cognition, guide treatment strategy, not the threat of motor fluctuations and dyskinesia. 2. Do not delay symptomatic therapy when motor and social activities are affected. 3. Use medications as just one component of the treatnlent plan. Give the patient responsibility for some aspects of treatment. 4. Avoid pursuing constant dopanlinergic

stimulation to high doses of dopaminergic drugs (greater than 1500 levodopa equivalents per day). Accept some motor fluctuations. 5. Periodically check patient's need for various drugs to reduce polypharmacy and its complications. IS152 Parldnson's Disease: Who Should Have Surgery? Lang, AE. Toronto Western Hospital, University of Toronto, Toronto,

Ontario, Canada DBS o f the STN is now the surgical treatment of choice for PD. STN DBS has not been proven to be more effective than DBS of the GPi, however, there are advantages in terms of lower drug dosages and stimulation current requirements. The utility of thalamic DBS is limited because befit is largely restricted to tremor. DBS is now preferred to lesioning due to its adaptability, reversibility and particularly safety for bilateral application. STN DBS can reproduce the clinical benefit of levodopa with the major advantages of profound improvements in motor fluctuations and dyskinesias. Symptoms persisting in the best "on" response to levodopa (e.g. dysarthria, freezing, postural instability) are also largely unaffected by DBS. Thus, disabling motor complications but with a preserved good response to levodopa is the main indication for surgery. Significant cognitive dysfunction is a contraindication for surgery since further cognitive decline may occur in such patients. A variety of psyclfiatric complications can occur due to the surgery, stinlulation, drug changes, or problems with psychosocial adjustment. Preoperative active psychiatric problems (e.g. major depression) should be treated and careful psychiatric follow-up is important in the postoperative period. Surgery should not be offered before an adequate trial of antiparkinson medication. Nor should it be delayed until the patient's work, social and family lives have been compromised by a state of invalidism. Careful patient selection and treatment by an experienced team can provide outcomes with STN DBS that have longlasting profound beneficial effects on patient disability and quality of life. IS153 MOvelnent Disorders: What Goes Wrong in the Basal Ganglia? HaUelt, M. Human Motor Control Section, NINDS, NIH, Bethesda,

MD, USA The basal ganglia may play many roles, but the most obvious has to do with the control of movement. Moreover, it also seems obvious that disorders of the basal ganglia lead to either too nmch or to too little movement. Tiffs suggests that a role for the basal ganglia in normal movement is to help select the muscles that will be involved in a movement. A model o f basal ganglia function, perhaps oversimplified, consists of the direct and indirect pathways. Since the direct pathway is excitatory, it might be responsible for aiding movement selection. The indirect pathway is inhibitory and might be responsible for aiding inhibition of undesired movements. The whole process can be conceived of as a mechalfiSnl of "surround inhibition," and currently there is evidence that there is such a process in normal movement. In Parkinson's Disease, the major problem is bradykinesia, and the basal ganglia dysfunction is lack of movement facilitation. In dystonia, the major problem is overflow movement, and the basal ganglia dysfunction is failure of surround inlfibition. In dyskinesias such as Huntington's Disease and levodopa induced dyskinesias, movements are selected and released by the basal ganglia in the absence of a voluntary drive. IS154 A Cliuidan's Guide to Tremor Joe Jankovic. Professor of Neurology, Director, Parkinson's Disease

Center and Movement Disorders Clinic, Department of Neurology', Baylor College of Medicine, Houston, Texas