Parkinson Disease: New England

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.

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.

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.

Kazantsev AG, Kolchinsky AM. · Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Bldg 114, 3300 16th St, Charlestown, MA 02129-4404, USA. · Arch Neurol. · Pubmed #19064744 No free full text.

Abstract: Selective death of nigrostriatal neurons, which leads to Parkinson disease, is explained by misfolding of brain protein alpha-synuclein. Herein, we review the data supporting this concept, propose a scheme of events leading to synuclein-induced neuronal death, and discuss protein deacetylase sirtuins as new potential therapeutic targets involved in this process.

Staropoli JF. · Department of Pathology, Massachusetts General Hospital, Gray-Jackson 249, MGH, 55 Fruit St Boston, MA 02114-2696, USA. · Bioessays. · Pubmed #18623069 No free full text.

Abstract: Dysregulation of genes that control cell-cycle progression and DNA repair is a hallmark of tumorigenesis. It is becoming increasingly apparent, however, that these defects also contribute to degeneration of post-mitotic neurons under certain conditions. The gene for ataxia-telangiectasia mutated (ATM) is a prototype for this dual mechanism of action, with loss-of-function mutations causing not only selective degeneration of cerebellar neurons but also increased susceptibility to breast cancer and hematologic malignancy. Increased dosage of amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia of Alzheimer type and may also contribute to acute leukemia and transient myeloproliferative disorder. The gene parkin, loss-of-function mutations in which account for about half of cases of early-onset Parkinson disease, has been identified as a candidate tumor suppressor gene by several groups. Parkin is deleted or downregulated in several tumor types, and its re-expression sensitizes derivative cell lines to inhibitors of cell-cycle progression. The overlap of molecular pathways implicated in cancer and neurodegeneration challenges long-held notions about differentiated cellular states and may open the door to novel therapeutic approaches to both groups of disorders.

Salamone JD, Ishiwari K, Betz AJ, Farrar AM, Mingote SM, Font L, Hockemeyer J, Müller CE, Correa M. · Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · Parkinsonism Relat Disord. · Pubmed #18585081 No free full text.

Abstract: Adenosine A(2A) antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A(2A) antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function.

Saint-Hilaire MH. · Parkinson's Disease and Movement Disorders Center, Boston University School of Medicine, MA 02118 USA. · Med Health R I. · Pubmed #18549039 No free full text.

This publication has no abstract.

Salamone JD, Betz AJ, Ishiwari K, Felsted J, Madson L, Mirante B, Clark K, Font L, Korbey S, Sager TN, Hockemeyer J, Muller CE. · Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · Front Biosci. · Pubmed #18508458 No free full text.

Abstract: Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A2A antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A2A antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A2A antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A2A antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects. Adenosine A2A antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.

Calabrese EJ. · Department of Public Health, Environmental Health Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA. · Crit Rev Toxicol. · Pubmed #18432420 No free full text.

Abstract: This article is a comprehensive assessment of the quantitative features of the dose response for neuroprotective agents and their underlying mechanistic foundations. The data were derived from published studies using numerous primary neuronal cell cultures and neuronal cell lines. These biological models assessed normal developmental and aging processes, preconditioning adaptive responses, and various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The nature of the dose response was generally U-shaped with quantitative features similar to the hormetic dose-response model and independent of biological model, endpoint measured, and chemical class. The agents displaying the U-shaped dose response for neuronal survival include numerous endogenous agonists, plant-derived agents, synthetic drugs, and widely used chemicals including potent neurotoxins. That neuroprotective agents display similar dose-response relationships regardless of experimental system, potency, and endpoint is an important observation with widespread biomedical and clinical implications.

Kinoshita J, Clark T. · Alzheimer Research Forum, Waltham, MA, USA. · Methods Mol Biol. · Pubmed #18368375 No free full text.

Abstract: The Alzheimer Research Forum Web site ( http://www.alzforum.org ) is an independent research project to develop an online community resource to manage scientific knowledge, information, and data about Alzheimer disease (AD). Its goals are to promote rapid communication, research efficiency, and collaborative, multidisciplinary interactions. Introducing new knowledge management approaches to AD research has a potentially large societal value. AD is among the leading causes of disability and death in older people. According to the Alzheimer's Association, four million Americans currently suffer from AD. That number is expected to escalate to over 10 million in coming decades. Patients progress from memory loss to a bedridden state over many years and require near-constant care. In addition to imposing a heavy burden on family caregivers and society at large, AD and related neurodegenerative disorders are among the most complex and challenging in biomedicine. Researchers have produced an abundance of data implicating diverse biological mechanisms. Important factors include genes, environmental risks, changes in cell functions, DNA damage, accumulation of misfolded proteins, cell death, immune responses, changes related to aging, and reduced regenerative capacity. Yet there is no agreement on the fundamental causes of AD. The situations regarding Parkinson, Huntington, and amyotrophic lateral sclerosis (ALS) are similar. The challenge of integrating so much data into testable hypotheses and unified concepts is formidable. What is more, basic understanding of these diseases needs to intersect with an equally complex universe of pharmacology, medicinal chemistry, animal studies, and clinical trials. In this chapter, we will describe the approaches developed by Alzforum to achieve knowledge integration through information technology and virtual community-building. We will also propose some future directions in the application of Web-based knowledge management systems in neuromedicine.

Astradsson A, Cooper O, Vinuela A, Isacson O. · NINDS Udall Parkinson's Disease Research Center of Excellence, Harvard University and McLean Hospital, Belmont, Massachusetts 02478, USA. · Neurosurg Focus. · Pubmed #18341409 No free full text.

Abstract: In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression as reasons for variable outcome and for some of the side effects observed in these clinical trials. To address ethical, practical, and technical issues related to the use of fetal cell sources, alternative sources of therapeutic dopaminergic neurons are being developed. The authors describe the progress in enrichment and purification strategies of stem cell-derived dopaminergic midbrain neurons. They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease.

Friedman JH, Millman RP. · Neuro Health Parkinson's Disease and Movement Disorders, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. · CNS Spectr. · Pubmed #18323762 links to  free full text

Abstract: Although Parkinson's disease is defined by its motor symptoms, the symptoms that are most devastating to patients and caregivers are dementia and psychosis. In addition, sleep has a tremendous impact on patient well being and quality of life. Eighty percent to 90% of Parkinson's disease patients have a sleep disorder affecting their ability to fall asleep, ability to stay asleep, dreams, motor activity during sleep, post-sleep behavior, or daytime somnolence. Treatment plans for patients with Parkinson's disease who experience sleep disorders aim to improve nighttime sleep or daytime wakefulness, and treatment options vary by sleep disorder.

Wilkins KM, Ostroff R, Tampi RR. · Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. · J Geriatr Psychiatry Neurol. · Pubmed #18287164 No free full text.

Abstract: Electroconvulsive therapy (ECT) is well established as a safe and effective treatment for several psychiatric disorders. Responsiveness to ECT does not abate with age, and data indicate that the use of ECT in the treatment of psychiatric disorders in the elderly persons has increased in recent decades. Special consideration must be given to the baseline cognitive abilities of an elderly patient prior to treatment with ECT. Much of the literature on the use of ECT in the elderly persons has focused on the treatment of mood disorders, whereas less research has been devoted to its use in the treatment of other psychiatric conditions. Although depressive syndromes remain the most common indication for ECT in the elderly persons, clinicians treating elderly patients should remain aware of the safety and efficacy of this treatment modality with other psychiatric disorders. This review examines the literature on the use of ECT in elderly patients with some common neuropsychiatric disorders including catatonia, bipolar mania, schizophrenia, dementia with behavioral disturbance, and Parkinson's disease.

Arle JE, Shils JL. · Department of Neurosurgery, The Lahey Clinic, Tufts University School of Medicine, 41, Mall Road, Burlington, MA 01867, United States. · Neurophysiol Clin. · Pubmed #18083501 No free full text.

Abstract: Intraoperative monitoring (IOM) adds new information to intraoperative surgical decision-making. When presented clearly and accurately, it can help guide decision processes during the procedure, but can be a detriment overall if the information is inaccurate or misleading. Troubleshooting abilities and vigilance of the IOM staff play a large role in bolstering the level of trust a surgeon develops in IOM. Additionally, a surgeon may impart his own interpretation and experience with this new information that can undermine or enhance its impact on the case. In this article, we explore these issues with IOM in general and as they relate to the special context of DBS for movement disorders.

Friehs GM, Park MC, Goldman MA, Zerris VA, Norén G, Sampath P. · Department of Clinical Neurosciences Program in Neurosurgery and New England Gamma Knife Center, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA. · Neurosurg Focus. · Pubmed #18081480 No free full text.

Abstract: Stereotactic radiosurgery (SRS) with the Gamma Knife and linear accelerator has revolutionized neurosurgery over the past 20 years. The most common indications for radiosurgery today are tumors and arteriovenous malformations of the brain. Functional indications such as treatment of movement disorders or intractable pain only contribute a small percentage of treated patients. Although SRS is the only noninvasive form of treatment for functional disorders, it also has some limitations: neurophysiological confirmation of the target structure is not possible, and one therefore must rely exclusively on anatomical targeting. Furthermore, lesion sizes may vary, and shielding adjacent radiosensitive neural structures may be difficult or impossible. The most common indication for functional SRS is the treatment of trigeminal neuralgia. Radiosurgical treatment for epilepsy and certain psychiatric illnesses is performed in several centers as part of strict research protocols, and radiosurgical pallidotomy or medial thalamotomy is no longer recommended due to the high risk of complications. Radiosurgical ventrolateral thalamotomy for the treatment of tremor in patients with Parkinson disease or multiple sclerosis, as well as in the treatment of essential tremor, may be indicated for a select group of patients with advanced age, significant medical conditions that preclude treatment with open surgery, or patients who must receive anticoagulation therapy. A promising new application of SRS is high-dose radiosurgery delivered to the pituitary stalk. This treatment has already been successfully performed in several centers around the world to treat severe pain in patients with end-stage cancer.

Logroscino G, Traynor BJ, Hardiman O, Chio' A, Couratier P, Mitchell JD, Swingler RJ, Beghi E, Anonymous00066. · Department of Epidemiology HSPH 3-819 Harvard University, 677 Huntington Avenue, Boston, Massachusetts 02115, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #18079297 No free full text.

Abstract: Amyotrophic lateral sclerosis (ALS) is a relatively rare disease with a reported population incidence of between 1.5 and 2.5 per 100,000 per year. Over the past 10 years, the design of ALS epidemiological studies has evolved to focus on a prospective, population based methodology, employing the El Escorial criteria and multiple sources of data to ensure complete case ascertainment. Five such studies, based in Europe and North America, have been published and show remarkably consistent incidence figures among their respective Caucasian populations. Population based studies have been useful in defining clinical characteristics and prognostic indicators in ALS. However, many epidemiological questions remain that cannot be resolved by any of the existing population based datasets. The working hypotheses is that ALS, like other chronic diseases, is a complex genetic condition, and the relative contributions of individual environmental and genetic factors are likely to be relatively small. Larger studies are required to characterise risks and identify subpopulations that might be suitable for further study. This current paper outlines the contribution of the various population based registers, identifies the limitations of the existing datasets and proposes a mechanism to improve the future design and output of descriptive epidemiological studies.

Leegwater-Kim J, Waters C. · Lahey Clinic, Department of Neurology, 41 Mall Road, Burlington, MA 01805, USA. · Expert Rev Neurother. · Pubmed #18052761 No free full text.

Abstract: For decades, the cornerstone of treatment for Parkinson's disease (PD) has been levodopa, which provides a smooth clinical response early in the course of disease. However, many PD patients develop motor complications on long-term levodopa therapy. Catechol-O-methyltransferase (COMT) is a selective and widely distributed enzyme involved in the catabolism of levodopa. Tolcapone and entacapone are selective and potent COMT inhibitors that slow the metabolism of levodopa, thus prolonging its effects. While both drugs act peripherally, tolcapone also inhibits COMT in the CNS. Tolcapone has been shown to be an effective adjunct in the treatment of PD in Phase II and III clinical trials, improving motor fluctuations and reducing levodopa requirements. Rare reports of severe hepatotoxicity, however, limited tolcapone's implementation in the treatment of PD. A reappraisal of the data for tolcapone treatment in PD has found that this risk is very small if proper hepatic monitoring guidelines are followed. This article reviews the pharmacology and clinical data on tolcapone, with particular focus on drug safety and the future role of tolcapone therapy in the treatment of PD.

Potenza MN, Voon V, Weintraub D. · Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, CT 06519, USA. · Nat Clin Pract Neurol. · Pubmed #18046439 No free full text.

Abstract: Impulse control disorders (ICDs) constitute a group of relatively common psychiatric conditions. ICDs typically involve pleasurable or hedonic behaviors (e.g. gambling, shopping or sex) that are performed repetitively, excessively or compulsively, to an extent that interferes in major areas of life functioning. Over the past decade, case reports, case studies and controlled examinations have reported ICDs in neurological patients, particularly those with Parkinson's disease (PD). A relationship between dopamine agonist treatment and ICDs was initially suggested on the basis of clinical observations, and subsequent systematic studies have provided more-substantial support for this association. Ongoing studies of the clinical characteristics of individuals with PD with and without ICDs suggest that certain individuals might be at increased risk of developing ICDs during PD treatment. Emerging data suggest that the association between dopamine agonists and ICDs extends into other neurological patient populations in which these agents are employed, such as those with restless legs syndrome. In this article, we summarize current knowledge regarding ICDs, review their relationships with PD and its treatments, provide practical clinical recommendations based on existing data, and suggest avenues for future research directed at advancing clinical care strategies.

Picciotto MR, Zoli M. · Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA. · Front Biosci. · Pubmed #17981563 No free full text.

Abstract: Epidemiological studies have identified a negative correlation between smoking and the development of neurodegenerative disorders such as Parkinson's disease, and in some studies, Alzheimer's disease. These findings have been attributed to the ability of nicotine to act as a neuroprotective agent. A large number of studies demonstrate that nicotine can protect against neuronal death in vitro and in vivo, and the mechanisms underlying the ability of nicotine to protect against excitotoxicity and amyloid-? toxicity are beginning to be elucidated. Despite the compelling evidence that nicotine is neuroprotective, it is clear that nicotine can be toxic under some circumstances. The balance between nicotine neuroprotection and toxicity depends on dose, developmental stage and regimen of administration. Therefore, a full understanding of the molecular and cellular effects of nicotine on signaling pathways relevant to neuronal survival is critical for informed drug discovery of nicotinic compounds to combat human neurodegeneration. This review summarizes recent studies related to the mechanisms underlying nicotine-mediated neuroprotection, and addresses issues that are relevant to use of nicotine as a neuroprotective agent in vivo.

Gugger JJ, Wagner ML. · School of Pharmacy, University of Connecticut, Storrs, CT, USA. · Ann Pharmacother. · Pubmed #17925503 No free full text.

Abstract: OBJECTIVE: To describe the clinical features of rapid eye movement (REM) sleep behavior disorder (RBD), evaluate treatment options, and discuss management of patients with comorbid diseases. DATA SOURCES: A MEDLINE search (1977-April 2007) using the terms REM sleep behavior disorder, narcolepsy, parkinsonian disorders, levodopa, dopamine agonists, clonazepam, benzodiazepines, and melatonin was used to retrieve relevant articles. The reference sections of all articles and texts were scanned for additional literature. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. There were no specific criteria for inclusion of articles in this review. DATA SYNTHESIS: RBD is characterized by enactment of dream content resulting from the loss of normal skeletal muscle atonia during REM sleep. RBD occurs mainly in geriatric patients and in patients with neurodegenerative diseases, especially parkinsonian diseases. The presence of idiopathic RBD may be a sign of an underlying parkinsonian syndrome. Development of RBD may be one of the first manifestations of Parkinson's disease or other parkinsonian syndromes. An acute form of RBD can be drug-induced or occur on drug withdrawal. The potential for injury to the patient and his or her bed partner is as high as 96%. Controlled trials are unavailable for most agents used in the treatment of RBD, although clonazepam is an effective first-line agent and can provide rapid and complete symptom remission based on evidence from 3 large case series. Patients who cannot tolerate clonazepam or who have a suboptimal response may benefit from melatonin alone or as an adjunct. Both drugs are generally well tolerated when taken at bedtime. Management of patients with RBD becomes complicated due to the high incidence of neurologic comorbidity. CONCLUSIONS: Clonazepam is the treatment of choice for patients with RBD. The drug is efficacious and has a low incidence of adverse effects. Melatonin is a viable second-line or adjunctive treatment.

Aiken CB. · Department of Psychiatry, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · J Clin Psychiatry. · Pubmed #17854248 No free full text.

Abstract: OBJECTIVE: To assess the risks and benefits of pramipexole in psychiatric populations. DATA SOURCES: A PubMed search was performed using the keywords pramipexole and ropinirole, which identified 500 articles. STUDY SELECTION: All clinical studies in psychiatric populations were included in the primary review (24 articles). Studies involving other populations were then reviewed to evaluate potential risks and benefits not identified in the psychiatric studies. DATA EXTRACTION: Effect sizes were calculated from controlled studies. Rates of intolerable side effects and manic switching were estimated by pooled analysis of controlled and uncontrolled studies. DATA SYNTHESIS: Pramipexole has a large effect size (0.6-1.1) in the treatment of both bipolar and unipolar depression with a low short-term rate of manic switching in bipolar patients (1% mania, 5% hypomania). The pooled discontinuation rate for all reasons was 9%. Pramipexole is neuroprotective and exerts beneficial effects on sleep architecture. Pramipexole is associated with 3 rare but serious side effects: sleep attacks, which have only occurred in Parkinson's disease; compulsive behaviors and pathologic gambling, which have occurred in Parkinson's disease and restless legs syndrome; and psychosis, which has occurred in both psychiatric and neurologic populations. CONCLUSIONS: Pramipexole is an important therapeutic option for treatment-resistant bipolar and unipolar depression; further studies are warranted to evaluate its safety in psychiatric patients.

Kern DS, Kumar R. · College of Medicine, University of Vermont, Burlington, Vermont, USA. · Neurologist. · Pubmed #17848864 No free full text.

Abstract: BACKGROUND: Deep brain stimulation (DBS) for the treatment of neurologic diseases has markedly increased in popularity over the past 15 years. This review primarily focuses on movement disorder applications and efficacy of DBS, but also briefly reviews other promising new and old uses of DBS. REVIEW SUMMARY: A multidisciplinary team consisting of a movement disorders neurologist, a functional neurosurgeon, and a neuropsychologist optimally selects patients for DBS. Patients must be significantly disabled despite optimal medical therapy and be cognitively healthy without significant psychiatric disorders. Although this surgery is elective, it should not be withheld until the patient suffers marked loss of quality of life. Patients must have support from caregivers and postoperatively multiple DBS programming visits may be required. DBS of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) significantly improves motor performance, activities of daily living, and quality of life in advanced Parkinson disease. In addition, STN DBS allows for marked reductions of antiparkinson medication. Stimulation of the ventralis intermedius nucleus of the thalamus is an effective treatment for essential tremor with sustained long-term effects. The GPi may be the preferred site of stimulation for dystonia with movement scores typically improved by 75% in patients with primary dystonia. CONCLUSIONS: DBS is an effective surgical treatment for movement disorders with sustained long-term benefits. Further research is ongoing to better understand the mechanism of DBS, refine the hardware to improve efficacy and reduce adverse effects, and identify additional applications and new anatomic targets.

Chou KL, Evatt M, Hinson V, Kompoliti K. · Department of Clinical Neurosciences, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. · Mov Disord. · Pubmed #17659637 No free full text.

Abstract: A significant number of patients with Parkinson's disease (PD) experience sialorrhea. This problem can cause social embarrassment, and because saliva pools in the mouth, may lead to aspiration pneumonia. Sialorrhea in PD is thought to be caused by impaired or infrequent swallowing, rather than hypersecretion. Oral medications, botulinum toxin injections, surgical interventions, radiotherapy, speech therapy, and trials of devices may be used to treat sialorrhea in PD, but few controlled trials have been published. This article reviews current knowledge regarding the frequency, etiology, assessment, and treatment of sialorrhea in PD.

Hung AY, Schwarzschild MA. · Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Curr Opin Neurol. · Pubmed #17620885 No free full text.

Abstract: PURPOSE OF REVIEW: To summarize recently published results of neuroprotection trials for Parkinson's disease, and discuss them in the context of evolving concepts in clinical study design and animal models. RECENT FINDINGS: Despite compelling preclinical evidence from laboratory models suggesting potential neuroprotective benefits, the antioxidant, antiapoptotic, antiexcitotoxic, immunomodulatory and neurotrophic agents studied to date have not shown clear benefit in human studies. The futility study design, an alternative approach focused on efficiently excluding less promising compounds, has been adopted recently to investigate four candidate neuroprotectants. A delayed-start trial design has also been introduced in a study of the monoamine oxidase inhibitor rasagiline, demonstrating a possible neuroprotective effect as well as its clear symptomatic benefit. In parallel with these clinical innovations, preclinical research initiatives are identifying new animal models that more closely resemble the clinical course and pathology of Parkinson's disease. SUMMARY: Angst over disappointing results of neuroprotection trials in Parkinson's disease has engendered efforts to refine animal models at one end of the therapeutics pipeline, and to optimize clinical trial design at the other. Building on new insights into the genetics, epidemiology and pathogenesis of Parkinson's disease, these recent improvements in 'translational infrastructure' will enhance the prospects of achieving the critical goal of slowing the progression of disability.

Lau FC, Shukitt-Hale B, Joseph JA. · USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · Subcell Biochem. · Pubmed #17612057 No free full text.

Abstract: It is estimated that by the year 2050 the elderly (aged 65 or older) population will double the population of children (aged 0-14) for the first time in history. The expansion of the elderly population has already taken a toll on health care systems. In order to alleviate the health care costs and increase the quality of living in the aging population, it is crucial to explore methods that may retard or reverse the deleterious effects of aging. Inflammation and oxidative stress play important roles in brain aging. Inflammatory markers, as well as cellular and molecular oxidative damage, increase during normal brain aging. This increase is accompanied by the concomitant decline in cognitive and motor performance in the elderly population, even in the absence of neurodegenerative diseases. Epidemiological studies have shown that consumption of diets rich in antioxidant and anti-inflammatory agents, such as those found in fruits and vegetables, may lower the risk of developing age-related neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Research from our laboratory suggests that dietary supplementation with fruit or vegetable extracts can decrease the age-enhanced vulnerability to oxidative stress and inflammation. Additional research suggests that the polyphenolic compounds found in fruits such as blueberries may exert their beneficial effects through signal transduction and neuronal communication. Thus, nutritional intervention may exert therapeutic protection against age-related deficits and neurodegenerative diseases.