Parkinson Disease: Illinois

Desai BS, Monahan AJ, Carvey PM, Hendey B. · Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA. · Cell Transplant. · Pubmed #17503739 No free full text.

Abstract: The blood-brain barrier (BBB) is a tightly regulated barrier in the central nervous system. Though the BBB is thought to be intact during neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence argues otherwise. Dysfunction of the BBB may be involved in disease progression, eliciting of peripheral immune response, and, most importantly, altered drug efficacy. In this review, we will give a brief overview of the BBB, its components, and their functions. We will critically evaluate the current literature in AD and PD BBB pathology resulting from insult, neuroinflammation, and neurodegeneration. Specifically, we will discuss alterations in tight junction, transport and endothelial cell surface proteins, and vascular density changes, all of which result in altered permeability. Finally, we will discuss the implications of BBB dysfunction in current and future therapeutics. Developing a better appreciation of BBB dysfunction in AD and PD may not only provide novel strategies in treatment, but will prove an interesting milestone in understanding neurodegenerative disease etiology and progression.

Muma NA. · Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois, USA. · J Neuropathol Exp Neurol. · Pubmed #17413316 No free full text.

Abstract: Transglutaminase catalyzes a covalent bond between peptide-bound glutamine residues and either lysine-bound peptide residues or mono- or polyamines. Multiple lines of evidence suggest that transglutaminase is involved in neurodegenerative diseases including Alzheimer disease, progressive supranuclear palsy, Huntington disease (HD), and Parkinson disease. In all of the neurodegenerative diseases examined to date, transglutaminase enzyme activity is upregulated in selectively vulnerable brain regions, transglutaminase proteins are associated with inclusion bodies characteristic of the diseases, and prominent proteins in the inclusion bodies are modified by transglutaminase enzymes. These prominent proteins in the inclusion bodies, including tau, alpha-synuclein, and huntingtin protein, are modified by transglutaminase in vitro and alpha-synuclein and huntingtin protein are modified in cells in culture. Similar changes in transglutaminase and transglutaminase-modified proteins are replicated in transgenic mouse models of the neurodegenerative diseases, including Huntington disease and progressive supranuclear palsy. Lastly, inhibition of transglutaminase either via drug treatments or molecular approaches is beneficial for the treatment of HD transgenic mice but has yet to be explored for the other neurodegenerative diseases. Further research is needed to determine the specific role(s) that transglutaminase plays in the pathophysiology of neurodegenerative diseases with possible implications for transglutaminase as a therapeutic target.

Logemann JA. · Department of Communication Sciences and Disorders, Northwestern University, Evanston, Illinois 60208, USA. · Semin Speech Lang. · Pubmed #17117348 No free full text.

Abstract: This article describes and compares methodologies for collecting data on the outcomes and efficacy of dysphagia treatments. Several examples are included that distinguish these various types of studies. Study designs that are unique to dysphagia such as assessing the immediate effectiveness of treatment strategies of the instrumental study are described.

Bevan MD, Atherton JF, Baufreton J. · Northwestern University, Department of Physiology, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. · Curr Opin Neurobiol. · Pubmed #17084618 No free full text.

Abstract: The motor symptoms of Parkinson's disease are associated with abnormal, correlated, low frequency, rhythmic burst activity in the subthalamic nucleus and connected nuclei. Research into the mechanisms controlling the pattern of subthalamic activity has intensified because therapies that manipulate the pattern of subthalamic activity, such as deep brain stimulation and levodopa administration, improve motor function in Parkinson's disease. Recent findings suggest that dopamine denervation of the striatum and extrastriatal basal ganglia profoundly alters the transmission and integration of glutamatergic cortical and GABAergic pallidal inputs to subthalamic neurons, leading to pathological activity that resonates throughout the basal ganglia and wider motor system.

Comella CL. · Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · J Neural Transm Suppl. · Pubmed #17017552 No free full text.

Abstract: Sleep disturbances are frequent in Parkinson disease. These disorders can be broadly categorized into those that involve nocturnal sleep and excessive daytime sleepiness. The disorders that are often observed during the night in PD include sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea, Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder. Excessive daytime sleepiness is also a common occurrence in PD. EDS can arise from several etiologies, and patients may have more than one etiology responsible. The causes of EDS include nocturnal sleep disorder with sleep deprivation and resulting daytime somnolence, the effect of drugs used to treat PD, and possibly neurodegeneration of central sleep/wake areas. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.

Goetz CG. · Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · J Neural Transm Suppl. · Pubmed #17017545 No free full text.

Abstract: Several new advances facilitate current understanding of the progression of Parkinson's disease. The application of statistical modeling techniques has helped to estimate rates of clinical decline in the context of symptomatic interventions. These approaches may allow a new means for testing neuroprotection effects even when patients are on dopaminergic treatment. Further, the development of new rating scales, specifically the Movement Disorder Society-initiated revision of the Unified Parkinson's Disease Rating Scale has capitalized on a greater clinical appreciation of non-motor elements of Parkinson's disease. Finally, adaptations of new technologies that are computer-based and enable data transmission from at-home environments allow researchers to capture disease impairment and disability with potentially greater precision and much more frequently than permissible in a hospital clinic or practice setting.

Chan CS, Surmeier DJ, Yung WH. · Department of Physiology and Institute for Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Neurosignals. · Pubmed #16772731 No free full text.

Abstract: Advances in research on globus pallidus (GP) suggest that this 'long thought to be' relay in the 'indirect pathway' plays a unique and critical role in basal ganglia function. The traditional idea of parallel processing within the basal ganglia is also challenged by recent findings. It is now clear that axons of GP neurons form large, perisomatic baskets around target neurons in all major basal ganglia nuclei, thereby exerting a profound influence on the output of the entire basal ganglia. GP neurons are autonomously active both in vivo and in vitro. It is believed that temporal information carried along the corticostriatopallidal pathway is critical for proper motor execution. The importance of appropriately controlled discharge of GP neurons is highlighted by psychomotor disorders such as Parkinson's disease, in which alterations in the pattern and synchrony of discharge in GP neurons are thought to contribute to motor symptoms. Several lines of evidence suggest that the aberrant activity of GP neurons following dopamine depletion is caused by alteration in the synaptic input from both striatum and subthalamic nucleus. In normal subjects, the capability of striatal input in translating cortical input into precisely timed responses in GP neurons is mediated by (1) the expression of postsynaptic GABA(A) receptor composed of subunits with fast kinetic properties; (2) an effective GABA reuptake system in terminating the action of synaptically released GABA, and (3) the existence of dendritic HCN channels that actively abbreviate the time course of the inhibitory postsynaptic potentials and reset rhythmic discharge. Despite the rapid pace in uncovering the elements that shape the activity along the striatopallidosubthalamic pathway, the origin of rhythmic, synchronized bursting of GP neurons seen in parkinsonism has not been fully established experimentally. Further elucidation of the factors that control the information transfer in the striatopallidal synapses is thus critical to our understanding of basal ganglia function and establishing treatment for Parkinson's disease and other basal ganglia disorders.

Soderstrom K, O'Malley J, Steece-Collier K, Kordower JH. · Department of Neurological Science, Research Center for Brain Repair, Rush University Medical Center, Chicago, IL 60612, USA. · Cell Transplant. · Pubmed #16719060 No free full text.

Abstract: Nonhuman primate models of Parkinson's disease (PD) have been invaluable to our understanding of the human disease and in the advancement of novel therapies for its treatment. In this review, we attempt to give a brief overview of the animal models of PD currently used, with a more comprehensive focus on the advantages and disadvantages presented by their use in the nonhuman primate. In particular, discussion addresses the 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydopyridine (MPTP), rotenone, paraquat, and maneb parkinsonian models. Additionally, the role of primate PD models in the development of novel therapies, such as trophic factor delivery, grafting, and deep brain stimulation, are described. Finally, the contribution of primate PD models to our understanding of the etiology and pathology of human PD is discussed.

Carvey PM, Punati A, Newman MB. · Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA. · Cell Transplant. · Pubmed #16719059 No free full text.

Abstract: Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD--or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD. We then evaluate the primary issue of the progressive loss of DA neurons, which, except for a few studies, has not been addressed in animal models of PD, even though this is the major pathological characteristic of the disease. Lastly, we discuss the possibility that more than one risk factor for PD may be necessary to develop an animal model that shows synergy--the progressive loss of DA neurons. Thus, the multiple hit hypothesis of PD-that is, the effect of more then one risk factor-may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans.

Logemann JA. · Department of Communication Sciences and Disorders, Northwestern University, 2240 Campus Drive, Evanston, IL 60208, USA. · Dysphagia. · Pubmed #16685468 No free full text.

Abstract: Randomized clinical trials (RCTs) are often known as the gold standard in treatment efficacy studies. This article defines the characteristics of RCTs and the factors that investigators must consider in designing clinical trials in dysphagia. Design issues unique to behavioral treatments often used in dysphagia are discussed. Ongoing RCTs in dysphagia are described including studies of (1) the effectiveness of the Shaker exercise versus standardized treatment in patients with severe dysphagia resulting from stroke or treatment for head and neck cancer who have been nonoral for at least three months; (2) the comparative effects of nectar- and honey-thickened liquids versus chin tuck posture and in patients with dementia or Parkinson's disease with or without dementia who aspirate on thin liquids; and (3) the comparative effects of muscle exercise versus sensory postural therapy for dysphagia resulting from treatment for head and neck cancer. Issues in generalizing from the results of clinical trials are also described.

Meredith SC. · Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC 6079, Chicago IL 60637, USA. · Ann N Y Acad Sci. · Pubmed #16533927 No free full text.

Abstract: Protein aggregation is a prominent feature of many neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases, as well as spongiform encephalopathies and systemic amyloidoses. These diseases are sometimes called protein misfolding diseases, but the latter term begs the question of what is the "folded" state of proteins for which normal structure and function are unknown. Amyloid consists of linear, unbranched protein or peptide fibrils of approximately 100 A diameter. These fibrils are composed of a wide variety of proteins that have no sequence homology, and no similarity in three-dimensional structures--and yet, as fibrils, they share a common secondary structure, the beta-sheet. Because of the prominence of amyloid deposits in many of these diseases, much effort has gone into elucidation of fibril structure. Recent advances in solid-state NMR spectroscopy and other biophysical techniques have led to the partial elucidation of fibril structure. Surprisingly at the time, for beta-amyloid, a set of 39-43-amino-acid peptides believed to play a pathogenic role in Alzheimer's disease, the beta-sheets are parallel with all amino acids of the sheets in-register. Since the time of those observations, however, it has become clear that there is no universal structure for amyloid fibrils. While many of the amyloid fibrils described thus far have a parallel beta-sheet structure, some have antiparallel beta-sheets, and other, more subtle structural differences among amyloids exist as well. Amyloids demonstrate conformational plasticity, the ability to adopt more than one stable tertiary fold. Conformational plasticity could account for "strain" differences in prions, and for the fact that a single polypeptide can form different fibril types with conformational differences at the atomic level. More recent data now indicate that the fibrils may not be the most potent or proximate mediators of cyto- and neurotoxicity. This damage is not confined to cell death, but also includes more subtle forms of damage, such as disruption of synaptic plasticity in the central nervous system. Rather than fibrils, prefibrillar aggregates, variously called "micelles," "protofibrils," or ADDLs (beta-amyloid-derived diffusible ligands in the case of beta-amyloid) may be the more proximate mediators of cell damage. These are soluble oligomers of aggregating peptides or proteins, but their structure is very challenging to study, because they are generally difficult to obtain in large enough quantities for high-resolution structural techniques, and they are temporally unstable, rapidly changing into more mature, and eventually fibrillar forms. Consequently, the mechanisms by which they disrupt cellular function are also not well understood. Nevertheless, three broad, overlapping, nonexclusive sets of mechanisms have been proposed as responsible for the cellular damage caused by soluble, oligomeric protein aggregates. These are: (1) disruption of cell membranes and their functions [e.g., by inserting into membranes and disrupting normal ion gradients]; (2) inactivation of normally folded, functional proteins [e.g., by sequestering or localizing transcription factors to the wrong cellular compartment]; and (3) "gumming up the works," by binding to and inactivating components of the quality-control system of cells, such as the proteasome or chaperone proteins.

O'Shaughnessy BA, Bendok BR, Parkinson RJ, Shaibani A, Walker MT, Shakir E, Batjer HH. · Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. · J Neurosurg. · Pubmed #16509477 No free full text.

Abstract: Chiari malformation Type I (CM-I), a condition defined by caudal descent of the cerebellar tonsils through the foramen magnum, is generally considered a congenital lesion. Several authors, however, have described an acquired form that appears identical to the congenital lesion on neuroimages. The most commonly reported cause of an acquired CM-I is cerebrospinal fluid diversion through a lumboperitoneal shunt. In this paper, the authors report the case of a patient in whom an acquired CM-I developed in association with a supratentorial arteriovenous malformation (AVM) of the brain. Development of the acquired CM was documented on serial magnetic resonance images. Moreover, the CM was seen to originate and worsen in concert with the clinicoradiological progression of the AVM. The underlying mechanism responsible for the acquired CM in this case is thought to be a high-flow venopathy of the transverse and sigmoid sinuses causing occlusion on the right and redirection of venous outflow into posterior fossa veins, with consequent venous congestion and swelling of the posterior fossa structures.

Buracchio T, Arvanitakis Z, Gorbien M. · Rush Alzheimer's Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, Ill 6012, USA. · Dement Geriatr Cogn Disord. · Pubmed #16174977 No free full text.

Abstract: As life expectancy continues to increase over time, dementia is becoming an increasingly more common problem and a major cause of disability in older persons. It is now more important than ever to identify and manage common causes of dementia given variations in disease course, treatments and the possibility for modification of risk factors. Dementia with Lewy bodies (DLB) is a dementia syndrome characterized by progressive cognitive decline, with fluctuating cognition, recurrent detailed and well-formed hallucinations, and parkinsonism. This article aims to provide an overview of current concepts of DLB, including a description of the key clinical features and neuropathology, neurochemistry, and genetics of DLB, then a discussion of the relationship of DLB with Alzheimer's disease and Parkinson's disease, and, finally, a summary of current management strategies available for this disorder.

Metman LV, O'Leary ST. · Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Mov Disord. · Pubmed #15822076 No free full text.

Abstract: When medications no longer provide patients with Parkinson's disease a reasonable quality of life due to the presence of levodopa-associated motor fluctuations and dyskinesias, surgical treatment is often pursued. Numerous studies have examined the antiparkinsonian efficacy of procedures currently available, but surprisingly few studies have evaluated their effect on motor response complications in a systematic, controlled manner, using appropriate instruments. Nonetheless, the combined evidence from uncontrolled case series and more recent randomized controlled trials reviewed here indicates that unilateral pallidotomy, bilateral pallidal deep brain stimulation, and bilateral subthalamic deep brain stimulation all substantially alleviate levodopa-induced dyskinesias and, to a lesser extent, motor fluctuations. Incorporation of standardized, validated instruments for the quantification of motor response complications in future surgical study protocols will not only allow more accurate comparison of different interventions but also will help physicians select the most appropriate procedure for their patients.

Goetz CG, Poewe W, Rascol O, Sampaio C. · Department of Neurological Sciences, Department of Pharmacology, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #15818599 links to  free full text

Abstract: The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

Bendok BR, Przybylo JH, Parkinson R, Hu Y, Awad IA, Batjer HH. · Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. · Neurosurgery. · Pubmed #15730593 No free full text.

Abstract: OBJECTIVE AND IMPORTANCE: To describe our experience with the transradial approach for posterior circulation neurointerventional procedures. To the best of our knowledge, this approach has not been described previously for intracranial neuroendovascular procedures. CLINICAL PRESENTATION: The clinical and imaging characteristics as well as periprocedural outcomes of patients treated for intracranial posterior circulation disease via the transradial approach were analyzed retrospectively. INTERVENTION: Between January 1 and October 21, 2003, four patients with posterior circulation disease (aneurysm, n = 1, and atherosclerotic stenosis, n = 3) were treated via the transradial approach because of tortuous brachiocephalic anatomy. Procedural success was 100%, and there were no procedural complications. No technical difficulties were encountered. CONCLUSION: The transradial approach is an alternative to the femoral approach for posterior circulation neuroendovascular intervention. This approach has several advantages over other approaches, and the vasculature can be less tortuous than that encountered during the femoral approach. These factors can result in increased device trackability and procedural ease.

Goetz CG. · Rush University Medical Center, Chicago IL 60612, USA. · Lancet Neurol. · Pubmed #15620847 No free full text.

This publication has no abstract.

Simuni T. · Parkinson's Disease and Movement Disorders Center, Department of Neurology, Feinberg School of Medicine, Northwestern University, 675 North St. Clair Street, Suite 20-100, Chicago, IL 60611, USA. · Neurol Clin. · Pubmed #15501360 No free full text.

This publication has no abstract.

Howden CW. · Division of Gastroenterology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. · Am J Med. · Pubmed #15478852 No free full text.

Abstract: Dysphagia affects a large and growing number of individuals in the United States, particularly the elderly and those who are neurologically impaired. Swallowing difficulties may be due to age-related changes in oropharyngeal and esophageal functioning as well as central nervous system diseases such as stroke, Parkinson disease, and dementia. Among institutionalized individuals, dysphagia is associated with increased morbidity and mortality. An appreciation of the physiology of swallowing and the pathophysiology of dysphagia is necessary for proper patient management. Careful history, physical examination, and evaluation of radiologic and endoscopic studies should differentiate oropharyngeal and esophageal etiologies of dysphagia and distinguish mechanical (anatomic) disorders from functional (motor) disorders. A significant percentage of patients with dysphagia have concomitant acid-related disorders that are managed best with proton pump inhibitor (PPI) therapy. Three of the currently available PPIs are manufactured as capsules containing enteric-coated granules that may be mixed with soft foods or fruit juices before oral administration to those with swallowing difficulties. In addition, omeprazole and lansoprazole may be administered via gastrostomy or nasogastric feeding tubes as suspensions in sodium bicarbonate. Novel dosage formulations of lansoprazole that may be appropriate for patients with dysphagia include the commercially manufactured lansoprazole strawberry-flavored enteric-coated granules for suspension and lansoprazole orally disintegrating tablets.

Roitberg B, Urbaniak K, Emborg M. · Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois 60612, USA. · Neurol Res. · Pubmed #15198860 No free full text.

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of the dopamine producing neurons projecting from the substantia nigra into the corpus striatum. Current medical therapy is limited and cannot stop or reverse the degeneration. Over the past 30 years, attempts were made to change the course of the disease by replacing the lost neurons with grafts from various sources. Recent controlled clinical trials of fetal cell transplantation for PD have had disappointing results. These events present an opportunity to examine the past developments and future direction of cell transplantation for PD.

Kim SI, Voshol H, van Oostrum J, Hastings TG, Cascio M, Glucksman MJ. · Midwest Proteome Center, Department of Biochemistry and Molecular Biology, Finch University of Health Sciences/Chicago Medical School, North Chicago, Illinois 60064, USA. · Neurochem Res. · Pubmed #15176488 No free full text.

Abstract: The term "proteome" describes the protein complement of a genome. Proteomes of cells are dynamic and are directly affected by environmental factors, such as stress and/or drug treatment, or as a result of aging and disease. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell's proteins into various subpopulations. In neuroscience, "neuromics" (proteomics in the central nervous system) is in its infancy, with a paucity of studies in the context of the brain. One of the objectives of this review is to illustrate the potential of neuromics to profile differences in the distribution of thousands of proteins as a function of disease markers. We have previously used this approach to determine the effects of varied postmortem interval in examining human brain tissue and to identify biomarkers. Here we review proteomic studies of schizophrenia, Alzheimer's disease, and Parkinson's disease. Experimental results regarding Parkinson's disease are presented to illustrate the potential of neuromics to identify pathways of pathogenesis and novel therapeutic targets.

Meredith GE, Halliday GM, Totterdell S. · Department of Cellular and Molecular Pharmacology, Chicago Medical School, Finch University of Health Sciences, 3333 Green Bay Road, North Chicago, IL 60054, USA. · Parkinsonism Relat Disord. · Pubmed #15120093 No free full text.

Abstract: The pace of development of new animal models of Parkinson's disease (PD) has increased dramatically in the recent past, primarily because of the identification of the protein, alpha-synuclein, in Lewy bodies in both idiopathic and familial PD. This discovery has allowed the production of transgenic models that incorporate a form of human, mutant alpha-synuclein from rare familial cases, and has enabled the search for Lewy-body-like aggregations of this protein in toxin-induced models. Indeed, alpha-synuclein-positive inclusions, some of which bear strong resemblance to Lewy bodies, have now been recognized and their formation investigated in several different, environmentally-induced and transgenic models. Nevertheless, these data have yet to provide a uniform theory of inclusion pathogenesis for PD. The aim of this review is not only to summarize the findings to date on alpha-synuclein-immunopositive inclusion bodies, including some new information on Lewy bodies, but also provide a concise viewpoint on their origin and formation in animal models. We will provide evidence for a predicted series of intracellular events that underlie inclusion formation. Triggered by oxidative and metabolic stress, chronic, toxin-treated animals, rather than transgenic models transfected with human alpha-synuclein, eventually produce inclusion bodies that most closely resemble early stages of Lewy bodies. Elucidating the common mechanisms in animal models is a first step towards understanding the role of Lewy bodies and their formation in Parkinson's disease.

Wolf WA. · Hines VA Hospital, Loyola University Chicago School of Medicine, Hines, IL 60141, USA. · Curr Opin Investig Drugs. · Pubmed #14619412 No free full text.

Abstract: Solvay is developing SLV-308 (SME-308), a partial dopamine D2 agonist and noradrenergic agonist with serotonin 5-HT1A agonist properties, for the potential oral treatment of Parkinson's disease (PD), panic and depression. By January 2001, SLV-308 had entered phase II trials for PD and phase I trials for anxiety and depression.

Smaga S. · Department of Family and Community Medicine, SIU Family Practice Center, Southern Illinois University School of Medicine, Carbondale, Illinois 62901, USA. · Am Fam Physician. · Pubmed #14596441 links to  free full text

Abstract: Tremor, a rhythmic, involuntary, oscillatory movement of body parts, is the most common movement disorder. Tremors are classified as rest or action tremors. Rest tremor occurs when the affected body part is completely supported against gravity. Action tremors are produced by voluntary muscle contraction and are further divided into postural, isometric, or kinetic tremors. This article describes clinical signs and symptoms of six tremor syndromes, including physiologic tremor, essential tremor, Parkinson's disease, toxic and drug-induced tremor, cerebellar tremor, and psychogenic tremor, and presents a detailed diagnostic approach to tremor. Although new technologies such as positron emission tomography and single photon emission computed tomography are under investigation for possible use in diagnosing specific tremor syndromes, they have no widespread applicability or use at this time. The history and physical examination remain the most important diagnostic tools available to clinicians in identifying and classifying tremor syndromes.

Kanner AM, Barry JJ. · Department of Neurological Sciences, Rush Medical College, Rush Epilepsy Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. · Epilepsy Behav. · Pubmed #14592635 No free full text.

Abstract: Depression is one of the most frequent comorbid psychiatric disorders identified in patients with neurological disorders. The prevalence rates range between 20 and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's disease. Despite these relatively high prevalence rates, depression remains underrecognized and undertreated in these patients. And yet, depression accounts for poor quality-of-life ratings and has a negative impact on the recovery from neurological symptoms. In this article, we review the epidemiological and clinical characteristics of mood disorders in patients with multiple sclerosis, Parkinson's disease, stroke, and epilepsy, and focus on the impact mood disorders have on the quality of life of these patients and on their recovery from their neurological deficits.