Parkinson Disease: US Eastern Zone

Thurman DJ, Stevens JA, Rao JK, Anonymous00002. · National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA. · Neurology. · Pubmed #18250292 No free full text.

Abstract: OBJECTIVE: To develop a practice parameter for screening methods and assessments of risk for falls pertaining to patients likely to be seen in neurology practices. METHODS: Relevant literature was systematically reviewed and strength of evidence classified based on the American Academy of Neurology's criteria (Level A: established; Level B: probable; Level C: possible). RESULTS: An increased risk of falls is established among persons with diagnoses of stroke, dementia, and disorders of gait and balance (Level A) and probable among patients with Parkinson disease, peripheral neuropathy, lower extremity weakness or sensory loss, and substantial vision loss (Level B). A history of falling in the past year strongly predicts the likelihood of future falls (Level A). Screening measures have been developed to further assess risks of falls, including functional assessments that may be useful (Levels B and C). Several of these assess overlapping neurologic functions--i.e., gait, mobility, and balance--and there is insufficient evidence to assess whether they offer benefit beyond that provided by a standard neurologic examination. CONCLUSIONS: Patients with neurologic or general conditions associated with an increased risk of falling should be asked about recent falls and further examined for the presence of specific neurologic deficits that predict falls, which include gait and balance disorders; deficits of lower extremity strength, sensation, and coordination; and cognitive impairments. If substantial risks of falls are identified, appropriate interventions that are described in other evidence-based guidelines may be considered.

Burke RE, Dauer WT, Vonsattel JP. · Department of Neurology, Columbia University Medical Center, New York, NY, USA. · Ann Neurol. · Pubmed #19067353 No free full text.

Abstract: Braak and colleagues have proposed that, within the central nervous system, Parkinson's disease (PD) begins as a synucleinopathy in nondopaminergic structures of the lower brainstem or in the olfactory bulb. The brainstem synucleinopathy is postulated to progress rostrally to affect the substantia nigra and cause parkinsonism at a later stage of the disease. In the context of a diagnosis of PD, made from current clinical criteria, the pattern of lower brainstem involvement accompanying mesencephalic synucleinopathy is often observed. However, outside of that context, the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations. The concept that lower brainstem synucleinopathy represents "early PD" rests on the supposition that it has a substantial likelihood of progressing within the human lifetime to involve the mesencephalon, and thereby cause the substantia nigra pathology and clinical parkinsonism that have heretofore defined the disease. However, the predictive validity of this concept is doubtful, based on numerous observations made in populations of aged individuals who, despite the absence of neurological signs, have brain synucleinopathy ranging up to Braak stages 4 to 6 at postmortem. Furthermore, there is no relation between Braak stage and the clinical severity of PD. We conclude that the relation between patterns of abnormal synuclein immunostaining in the human brain and the disease entity now recognized as PD remains to be determined.

Parkinson AJ. · Arctic Investigations Program, National Center for Preparedness, Detection, and Control of Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK 99508, USA. · Emerg Infect Dis. · Pubmed #18258069 links to  free full text

Abstract: On 3 occasions over the past 125 years, scientists from around the world have worked together to organize scientific and exploration activities in polar regions (www.ipy.org). The first International Polar Year (IPY) in 1881-1884 marked the first major coordinated international scientific initiative to collect standardized meteorological and geophysical data in polar regions. Fifteen expeditions led by 12 nations amassed a large amount of data, but the scientific value was diminished by disjointed publication efforts and lack of long-term institutional commitment; lessons were learned and corrected in subsequent polar years. The second IPY began in 1932. Forty-four nations led expeditions in the Arctic and Antarctic, resulting in greater understanding of the aurora, magnetism, and meteorology. Air and marine navigation, radio operations, and weather forecasting were greatly improved as a result. The third IPY, in 1957-58, was renamed the International Geophysical Year and capitalized on technologic advances developed during World War II. Technologic and scientific momentum was redirected toward research, particularly to studies of the upper atmosphere, a legacy that continues to the present day. Notable achievements included launching the first satellite, measurement of atmospheric greenhouse gases, delineating the system of mid-ocean ridges, and confirming the theory of plate tectonics.

Olanow CW, Stern MB, Sethi K. · Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, Annenberg 14-94, New York, NY 10029, USA. · Neurology. · Pubmed #19470958 No free full text.

Abstract: Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches.

Price A, Filoteo JV, Maddox WT. · Department of Psychology, Elizabethtown College, Elizabethtown, PA 17022, United States. · Neuropsychologia. · Pubmed #19428385 links to  free full text

Abstract: Measures of explicit rule-based category learning are commonly used in neuropsychological evaluation of individuals with Parkinson's disease (PD) and the pattern of PD performance on these measures tends to be highly varied. We review the neuropsychological literature to clarify the manner in which PD affects the component processes of rule-based category learning and work to identify and resolve discrepancies within this literature. In particular, we address the manner in which PD and its common treatments affect the processes of rule generation, maintenance, shifting and selection. We then integrate the neuropsychological research with relevant neuroimaging and computational modeling evidence to clarify the neurobiological impact of PD on each process. Current evidence indicates that neurochemical changes associated with PD primarily disrupt rule shifting, and may disturb feedback-mediated learning processes that guide rule selection. Although surgical and pharmacological therapies remediate this deficit, it appears that the same treatments may contribute to impaired rule generation, maintenance and selection processes. These data emphasize the importance of distinguishing between the impact of PD and its common treatments when considering the neuropsychological profile of the disease.

Lewitt PA. · Department of Neurology, Henry Ford Hospital, Detroit, MI, USA. · Neurology. · Pubmed #19365057 No free full text.

This publication has no abstract.

Williams JA, Imamura M, Fregni F. · Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. · J Rehabil Med. · Pubmed #19363560 No free full text.

Abstract: Brain stimulation for the treatment of neuropsychiatric diseases has been used for more than 50 years. Although its development has been slow, current advances in the techniques of brain stimulation have improved its clinical efficacy. The use of non-invasive brain stimulation has significant advantages, such as not involving surgical procedures and having relatively mild adverse effects. In this paper we briefly review the use of 2 non-invasive brain stimulation techniques, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as therapeutic approaches in physical and rehabilitation medicine. We also compare the effects of non-invasive central nervous system stimulation with techniques of non-invasive peri notpheral electrical stimulation, in order to provide new insights for future developments. Although the outcomes of these initial trials include some conflicting results, the evidence supports that rTMS and tDCS might have a therapeutic value in different neurological conditions. Studies published within the last year have examined new approaches of stimulation, such as longer intensities of stimulation, new electrode sizes for tDCS, novel coils for stimulation of deeper areas, and new frequencies of stimulation for rTMS. These new approaches need to be tested in larger clinical trials in order to determine whether they offer significant clinical effects.

Frost EA, Osborn I. · Department of Anesthesiology, the Mount Sinai Medical Center, 1 Gustave L. Levy Place, New York, NY, USA. · Int Anesthesiol Clin. · Pubmed #19359876 No free full text.

This publication has no abstract.

Bloomfield DM. · 1Cardiovascular Clinical Research, Merck Research Laboratories, Boston, Massachusetts, USA. · Clin Pharmacol Ther. · Pubmed #19295536 No free full text.

Abstract: Electrocardiograms (ECGs) in patients with Parkinson's disease are affected by artifacts related to muscle tremor. Malik et al. report methods used in QTc study in patients with Parkinson's disease that markedly reduce the noise and variance of QTc in a sample of ECGs that are undeniably difficult to interpret. This study adds significant experience and novel methods that have the potential to further enhance the evaluation of the effect of a drug on QTc.

Lanoix M. · Department of Philosophy and Religion, I.G. Greer Hall, Appalachian State University, PO Box 32104, Boone, North Carolina 28608-2104, USA. · Chronic Illn. · Pubmed #19276225 No free full text.

Abstract: The increasing numbers of individuals needing palliative services and changing the nature of these services bring about new challenges for the delivery and accessibility of timely and appropriate palliative care services. Socioeconomic factors are known to affect access but disease type is a factor which can negatively impact the availability of adequate palliative services. The purpose of this article is to examine the barriers to palliation for chronic illnesses that span long periods of time. My analysis centers on palliation for Parkinson's disease because it illustrates the difficulties of managing the chronic-palliative interface, and it also demonstrates how care is situated in an evolving network of professional and non-professional actors. I argue that insuring the availability of adequate palliative services entails negotiating the chronic-palliative interface, which, in turn, requires continued multi-disciplinary professional involvement as well as the integration and recognition of the care provided by family caregivers.

Troster AI. · Department of Neurology, University of North Carolina School of Medicine at Chapel Hill, 3114 Bioinformatics Building (CB 7025), Chapel Hill, NC 27599-7025, USA. · Front Biosci. · Pubmed #19273169 No free full text.

Abstract: Deep brain stimulation (DBS) experienced resurgence in the 1990s when limitations in pharmacotherapy and ablative surgery for movement disorders (including neuropsychological deficits) were appreciated. Subthalamic DBS for Parkinson's disease has received the most empirical attention and may entail cognitive and psychiatric adverse events in approximately 10% of patients. This article reviews the cognitive alterations after thalamic, pallidal, and subthalamic DBS for movement disorders (including, Parkinson's disease, essential tremor, and dystonia) and the possible etiology and mechanisms underlying neurobehavioral changes. Initial studies of neurobehavioral outcomes of DBS for emerging indications such as epilepsy, obsessive compulsive disorder, depression, Tourette's syndrome, and persistent vegetative or minimally conscious state are also reviewed. DBS for currently accepted indications appears safe from a cognitive standpoint in that the procedure is associated with typically transient, mild, and circumscribed cognitive alterations (most commonly in verbal fluency), and improved mood state and quality of life. A minority of patients experience more widespread, persistent, or serious cognitive and psychiatric sequelae, although research to date has failed to identify reliable risk factors for such adverse events.

Haber SN, Brucker JL. · Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA. · Front Biosci. · Pubmed #19273166 No free full text.

Abstract: Several lines of evidence indicate that the neural network that underlies the pathophysiology of obsessive-compulsive disorder and depression centers on the prefronto-basal ganglia system. Particularly involved are anterior cingulate cortex, the orbital prefrontal cortex, the ventral striatum, and parts of the thalamus. Additional integral parts of the network include, the amygdala, the midbrain dopamine cells and the serotonergic neurons. Collectively, these brain regions are involved in various aspects of reward-based learning and good decision-making skills. They are also associated with sadness and depression, pathological risk-taking, addictive behaviors, and obsessive-compulsive disorder. Two of the most successful deep brain stimulation targets for obsessive-compulsive disorder and depression are centered in white matter tracts. These targets were chosen for their central location and ability to capture specific ascending and descending connections, with a particular focus on fibers connecting the subgenual anterior cingulate and orbital cortex with the basal ganglia, thalamus, and amygdala. As more knowledge is obtained concerning the details of these connections, more precise targets may be possible.

Dadabhai A, Friedenberg FK. · Temple University Hospital, Temple University School of Medicine, Gastroenterology Section, Parkinson Pavilion, 8th Floor, 3401 North Broad Street, PA 19140, Philadelphia, USA. · Expert Opin Drug Saf. · Pubmed #19236223 No free full text.

Abstract: Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of approximately 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.

Morimoto RI, Cuervo AM. · Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA. · J Gerontol A Biol Sci Med Sci. · Pubmed #19228787 No free full text.

Abstract: All cells count on precise mechanisms that regulate protein homeostasis to maintain a stable and functional proteome. Alterations in these fine-tuned mechanisms underlie the pathogenesis of severe human diseases including, among others, common neurodegenerative disorders such as Alzheimer's or Parkinson's disease. A progressive deterioration in the ability of cells to preserve the stability of their proteome occurs with age, even in the absence of disease, and it likely contributes to different aspects of "normal" aging. A group of experts in different aspects of the biology of aging met recently to discuss the implications of altered protein homeostasis in aging, the current gaps in our understanding of the mechanisms responsible for proteome maintenance, and future opportunities for discovery in this area. We summarize here some of the key topics and main outcomes of the discussions.

Elshaikh MA, Underwood W, Soto DE. · Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. · Can J Urol. · Pubmed #19222889 No free full text.

Abstract: We report a case history of a patient with Parkinson's disease (PD) treated with androgen deprivation therapy (ADT) and external beam radiation for prostate cancer, who developed severe deterioration of his PD during ADT.

Olanow CW. · Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. · Neurology. · Pubmed #19221316 No free full text.

Abstract: A disease-modifying therapy is the most important unmet medical need in the treatment of Parkinson disease (PD). Laboratory studies have identified many promising candidate agents, but none has been proven to be neuroprotective in PD. A major limitation has been the development of an endpoint that accurately reflects the underlying disease state. This dramatically limits the potential for a new drug being approved as a disease-modifying agent in PD. For the present, the best opportunity to provide patients with PD with a disease-modifying effect is with agents that have been approved for their symptomatic effects. This article reviews currently available drugs for PD and considers the evidence that they might have neuroprotective effects in PD.

Marek K, Jennings D. · Institute for Neurodegenerative Disorders, New Haven, CT, USA. · Neurology. · Pubmed #19221310 No free full text.

Abstract: Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity-it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease--and a challenge--how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or alpha-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk.

Levy OA, Malagelada C, Greene LA. · Department of Neurology, Columbia University School of Medicine, New York, NY, USA. · Apoptosis. · Pubmed #19165601 No free full text.

Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder. Neuronal cell death in PD is still poorly understood, despite a wealth of potential pathogenic mechanisms and pathways. Defects in several cellular systems have been implicated as early triggers that start cells down the road toward neuronal death. These include abnormal protein accumulation, particularly of alpha-synuclein; altered protein degradation via multiple pathways; mitochondrial dysfunction; oxidative stress; neuroinflammation; and dysregulated kinase signaling. As dysfunction in these systems mounts, pathways that are more explicitly involved in cell death become recruited. These include JNK signaling, p53 activation, cell cycle re-activation, and signaling through bcl-2 family proteins. Eventually, neurons become overwhelmed and degenerate; however, even the mechanism of final cell death in PD is still unsettled. In this review, we will discuss cell death triggers and effectors that are relevant to PD, highlighting important unresolved issues and implications for the development of neuroprotective therapies.

Nass R, Merchant KM, Ryan T. · Department of Pharmacology and Toxicology, Center for Environmental Health, and Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. · Mol Interv. · Pubmed #19144901 No free full text.

Abstract: It has been over forty years since dopamine neuron degeneration in the substantia nigra and Lewy body formation within surviving cells were described as the pathological hallmarks of Parkinson's disease (PD). Although research in the intervening decades particularly in the last twenty-five years has yielded a variety of robust animal models and invaluable mechanistic insights into PD-associated neuronal dysfunction and cell death, therapeutic agents have not been forthcoming to alter the course of PD. Recently, the screening of experimental therapeutics for PD has been pursued through the use of genetically tractable models, such as the nematode Caenorhabditis elegans. This simple worm remarkably recapitulates the basic cellular and molecular pathways associated with PD, is amenable to facile genetic methods, and through the use of high-throughput screening technologies, provides powerful new opportunities for the in vivo identification of therapeutic targets. In this review we briefly describe the utility that the C. elegans model system may have for PD drug discovery.

Zuckerman LM. · Department of orthopaedic Surgery and Rehabilitation Medicine, Suny Downstate Medical Center, Brooklyn, NY, USA. · J Am Acad Orthop Surg. · Pubmed #19136427 No free full text.

Abstract: Parkinson's disease is a progressive neurologic disorder that affects the musculoskeletal system in multiple ways. As medication and surgical management of this disorder have improved, the life spans and quality of life of patients affected by it also have improved. With age, the risk of fracture, osteoarthritis, and osteopenia increase in patients with Parkinson's disease compared with the general population. The symptoms of Parkinson's disease predispose patients to gait abnormalities and loss of bone mass, which commonly result in falls and fracture. Although preventive measures such as medication, lifestyle changes, and vitamin replacement may help, surgical intervention is often indicated. Surgical treatment and postoperative management of both elective and emergent surgery are complicated and controversial.

Cohen SM, Elackattu A, Noordzij JP, Walsh MJ, Langmore SE. · Division of Otolaryngology, Head and Neck Surgery, Duke University, Durham, NC, USA. · Otolaryngol Clin North Am. · Pubmed #19134494 No free full text.

Abstract: The focus of this article is the palliative treatment of a variety of dysphonic conditions. Symptomatic relief of hoarseness can be achieved by voice therapy, augmentative alternative communication modalities, and surgery. The causes of dysphonia addressed herein include amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, stroke, head and neck cancers requiring glossectomy or laryngectomy, unilateral vocal fold paralysis, and presbyphonia. Palliative treatment of dysphonia and voice disorders provides symptomatic relief but not a cure of the underlying disease state. For these patients there are a number of palliative interventions that can greatly improve their quality of life.

LeWitt PA. · Department of Neurology, Henry Ford Hospital, and the Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48034, USA. · Parkinsonism Relat Disord. · Pubmed #19131040 No free full text.

Abstract: Levodopa serves as the gold standard of anti-parkinsonian therapy and nearly every patient with Parkinson's disease eventually receives this drug. To improve upon levodopa therapy, several forms of treatment have been devised to augment its actions, and new delivery systems are under development. This new research offers promise for improving outcomes with this highly effective therapy.

Gupta A, Dawson VL, Dawson TM. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Ann Neurol. · Pubmed #19127586 No free full text.

Abstract: Currently, there is no proven neuroprotective or neurorestorative therapy for Parkinson's disease (PD). Several advances in the genetics of PD have created an opportunity to develop mechanistic-based therapies that hold particular promise for identifying agents that slow and even halt the progression of PD, as well as restore function. Here we review many of the advances in the last decade regarding the identification of new targets for the treatment of PD based on understanding the molecular mechanisms of how mutations in genes linked to PD cause neurodegeneration.

Olanow CW, Kieburtz K, Schapira AH. · Department of Neurology, Mount Sinai School of Medicine, New York, USA. · Ann Neurol. · Pubmed #19127580 No free full text.

Abstract: The development of a neuroprotective therapy that slows, stops, or reverses neurodegeneration in Parkinson's disease (PD) is the single most important unresolved issue in the management of this disorder. Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of "nondopaminergic" features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease-modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems.

Fahn S. · Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA. · Ann Neurol. · Pubmed #19127577 No free full text.

Abstract: The motor complications associated with levodopa therapy, namely, fluctuations in motor response and dyskinesias, occur in the majority of Parkinson's disease patients. These complications can impair a patient's quality of life and even cause pronounced disability. "Off" states that result in freezing of gait and falling are disabling for many patients. Dyskinesias most commonly occur at peak dose and typically alternate with the wearing-off state. Once these problems appear, they usually persist, and the physician needs to make continual adjustments in medications to minimize these problems. Medical treatments should be attempted before treatments such as deep brain stimulation are considered because of the potential adverse effects that are associated with surgery. The timing of surgery, however, is also important because younger patients and less advanced patients tend to have a better outcome. There is thus a need for experienced and knowledgeable physicians and surgeons who are able to handle these motor complications. This review discusses available medications and surgical approaches, and their outcomes.