Parkinson Disease: Florida

Wider C, Wszolek ZK. · Department of Neurology, Cannaday Building 2E, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA. · Lancet Neurol. · Pubmed #19081502 No free full text.

This publication has no abstract.

Edwards TM, Myers JP. · Department of Zoology, University of Florida, Gainesville, FL 32611, USA. · Cien Saude Colet. · Pubmed #18813540 links to  free full text

Abstract: Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.

Dutta G, Zhang P, Liu B. · Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. · Fundam Clin Pharmacol. · Pubmed #18710400 No free full text.

Abstract: Research in the last two decades has unveiled an important role for neuroinflammation in the degeneration of the nigrostriatal dopaminergic (DA) pathway that constitutes the pathological basis of the prevailing movement disorder, Parkinson's disease (PD). Neuroinflammation is characterized by the activation of brain glial cells, primarily microglia and astrocytes that release various soluble factors that include free radicals (reactive oxygen and nitrogen species), cytokines, and lipid metabolites. The majority of these glia-derived factors are proinflammatory and neurotoxic and are particularly deleterious to oxidative damage-vulnerable nigral DA neurons. As a proof of concept, various immunologic stimuli have been employed to directly induce glial activation to model DA neurodegeneration in PD. The bacterial endotoxin, lipopolysaccharide (LPS), has been the most extensively utilized glial activator for the induction of inflammatory DA neurodegeneration. In this review, we will summarize the various in vitro and in vivo LPS PD models. Furthermore, we will highlight the contribution of the LPS PD models to the mechanistic studies of PD pathogenesis and the search for neuroprotective agents for the treatment of PD.

Zahodne LB, Fernandez HH. · Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA. · Drugs Aging. · Pubmed #18665659 No free full text.

Abstract: Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship between deep brain stimulation surgery and PD psychosis.When reduction in anti-PD medications to the lowest tolerated dose does not improve psychosis, further intervention may be warranted. Several atypical antipsychotic agents (i.e. clozapine, olanzapine) have been shown to be efficacious in reducing psychotic symptoms in PD; however, use of clozapine requires cumbersome monitoring and olanzapine leads to motor worsening. Studies of ziprasidone and aripiprazole are limited to open-label trials and case reports and are highly variable; however, it appears that while each may be effective in some patients, both are associated with adverse effects. While quetiapine has not been determined efficacious in two randomized controlled trials, it is a common first-line treatment for PD psychosis because of its tolerability, ease of use and demonstrated utility in numerous open-label reports. Cholinesterase inhibitors currently represent the most promising pharmacological alternative to antipsychotics. Tacrine is rarely tried because of hepatic toxicity, and controlled trials with donepezil have not shown significant reductions in psychotic symptoms, due perhaps to methodological limitations. However, results from an open-label study and a double-blind, placebo-controlled trial involving 188 hallucinating PD patients support the efficacy of rivastigmine. With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis. Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients. Finally, studies in the schizophrenia literature indicate that psychological approaches are effective in psychosis management but, to date, this strategy has been supported only qualitatively in PD, and further studies are warranted.

Streit WJ, Miller KR, Lopes KO, Njie E. · Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA. · Front Biosci. · Pubmed #18508444 No free full text.

Abstract: We have long promulgated the idea that microglial cells serve an entirely beneficial role in the central nervous system (CNS), not only as immunological sentinels to fend off potentially dangerous infections, but also as constitutively neuroprotective glia that help sustain neuronal function in the normal and especially in the injured CNS when microglia become activated. In recent years, we have reported on the presence of degenerating microglial cells, which are prominent in the brains of aged humans and humans with neurodegenerative diseases, and this has led us to propose a hypothesis stating that loss of microglia and microglial neuroprotective functions could, at least in part, account for aging-related neurodegeneration. In the current review, we sum up the many aspects that characterize microglial activation and compare them to those that characterize microglial senescence and degeneration. We also consider the possible role of oxidative stress as a cause of microglial degeneration. We finish up by discussing the role microglial cells play in terms of amyloid clearance and degradation with the underlying idea that removal of amyloid constitutes a microglial neuroprotective function, which may become compromised during aging.

Post KK, Singer C, Papapetropoulos S. · Division of Movement Disorders, Department of Neurology, University of Miami, Miller School of Medicine, Clinical Research Building, 1120 N.W. 14th Street, 13th Floor, Room 1349, Miami, FL 33136, USA. · Parkinsonism Relat Disord. · Pubmed #18486523 No free full text.

Abstract: Parkinson's disease (PD) has classically been characterized by features of motor dysfunction, but these may manifest only after the nigrostriatal system has incurred significant damage. However, recent evidence suggests that cardiac sympathetic denervation occurs early on in PD. This may trigger a shift in physicians' attention to features of cardiovascular dysautonomia and allow for the evolution of earlier screening techniques. MIBG and PET (6F-DA) scans have demonstrated the functional loss of postganglionic sympathetic cardiac neurons, while immunohistochemical stains have revealed signs of morphological degeneration. Given this information, various screening techniques have been proposed, though most are particular to PD patients with orthostatic hypotension (OH). This is a considerable drawback given that the prevalence of OH in PD patients is estimated to be 41%. We present the argument that a shift in focus is needed; investigators should look for other manners by which to screen patients that are not reliant upon blood pressure. In our point of view, the problem with using blood pressure as a measurement is that it can be affected by many other factors unrelated to cardiac denervation. This may be why many patients with PD cannot be detected using these techniques. In order to make further progress on this front, we believe that investigators should start looking for variables that are more purely dependent upon cardiac denervation. We give one possible example of such a variable in this paper using heart transplant patients as a model.

Fukui H, Moraes CT. · Neuroscience Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. · Trends Neurosci. · Pubmed #18403030 No free full text.

Abstract: Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations support a 'vicious cycle' theory which states that there is a feedback mechanism connecting these events in aging and age-associated neurodegeneration. Despite being an extremely attractive hypothesis, the bulk of the evidence supporting the mitochondrial vicious cycle model comes from pharmacological experiments in which the modes of mitochondrial enzyme inhibition are far from those observed in real life. Furthermore, recent in vivo evidence does not support this model. In this review, we focus on the relationship among the components of the putative vicious cycle, with particular emphasis on the role of mitochondrial defects on oxidative stress.

Ratnasamy C, Rossique-Gonzalez M, Young ML. · Division of Pediatric Cardiology, University of Miami/ Miller School of Medicine, PO Box 016960 (R-76), Miami, FL 33101, USA. · Curr Pharm Des. · Pubmed #18393874 No free full text.

Abstract: Atrioventricular reentrant tachycardia (AVRT) is the most common cause of supraventricular tachycardia in young children. In nearly 70% of cases, there is manifest preexcitation on electrocardiogram. In the rest, the accessory pathway is concealed. Drugs control AVRT by affecting conduction through the atrioventricular node (beta-blockers, digoxin, verapamil) or accessory pathway (flecainide, propafenone) or both (sotalol, amiodarone). Adenosine is the drug of choice in acute management of AVRT in hemodynamically stable children. In adenosine-resistant cases, intravenous flecainide, procainamide, esmolol, propafenone and amiodarone are other treatment options. Hypotension and bradycardia can occur during administration of these drugs. Verapamil may be used to treat AVRT using a concealed pathway. Verapamil should be avoided in infants and in patients with decreased cardiac function. In chronic management, catheter ablation is the preferred treatment in older children with frequent AVRT. In infants and small children, ablation is associated with higher risk, and pharmacologic management is recommended. Beta-blockers are the preferred first line drugs for chronic management. In patients with concealed accessory pathway, digoxin and calcium channel blockers are alternative options. Sotalol, flecainide, propafenone and amiodarone can be prescribed in resistant cases. Flecainide and propafenone should be avoided in children with structurally abnormal hearts because of a higher risk of proarrhythmia. The initiation of flecainide, propafenone and sotalol therapy is recommended in an inpatient setting to monitor for proarrhythmias.

Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, Romrell J, Rodriguez RL. · University of Florida, Movement Disorders Center, Gainesville, FL 32601, USA. · Stereotact Funct Neurosurg. · Pubmed #18334856 No free full text.

Abstract: Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.

Zahodne LB, Fernandez HH. · Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA. · CNS Spectr. · Pubmed #18323764 links to  free full text

Abstract: It is essential to recognize and treat psychosis in Parkinson's disease for several reasons. Studies have shown that psychosis in Parkinson's disease patients is a strong risk factor for nursing home placement. Psychosis may be the greatest source of stress for caretakers of Parkinson's patients; it is often persistent, and its presence markedly increases mortality. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's antiparkinsonian medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic is presently the treatment of choice. An emerging treatment option is acetylcholinesterase inhibitors. This article reviews what is currently known about the course, prognosis, and treatment strategies in Parkinson's disease psychosis.

Wider C, Wszolek ZK. · Department of Neurology, Mayo Clinic, Jacksonville, Fla. 32224, USA. · Neurodegener Dis. · Pubmed #18322368 No free full text.

Abstract: Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease.

Wider C, Wszolek ZK. · Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA. · Parkinsonism Relat Disord. · Pubmed #18267241 No free full text.

Abstract: Our knowledge regarding the genetics of Parkinson's disease (PD) and parkinsonism has evolved dramatically during the past decade, with the discovery of numerous loci and genes. The LRRK2 gene has emerged as the most commonly involved in both familial and sporadic PD. Several variants in LRRK2 and SNCA have been associated with an increased risk of sporadic PD. PRKN, PINK1 and DJ1 mutations cause early-onset recessively inherited PD. Autosomal dominant dementia and parkinsonism is caused by mutations in the MAPT gene, and in the most recently discovered PGRN gene.

Fernandez HH, Chen JJ. · Movement Disorders Center, University of Florida, McKnight Brain Institute, Gainesville, FL 32610, USA. · Pharmacotherapy. · Pubmed #18041937 No free full text.

Abstract: Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B prolong the activity of both endogenously and exogenously derived dopamine, making them an option either as monotherapy in early Parkinson's disease or as adjunctive therapy in patients treated with levodopa who are experiencing motor complications. In addition to symptomatic benefits, experimental data suggest that MAO-B inhibitors may be neuroprotective through MAO-B inhibition and other mechanisms that have yet to be clearly defined. The two available MAO-B inhibitors approved for use in the United States, rasagiline and selegiline, each provide symptomatic relief as monotherapy and as adjunctive therapy, and have shown potential disease-modifying effects in experimental models and clinical studies. Selegiline in a conventional tablet formulation is less bioavailable than rasagiline, resulting in limited potency. It also has amphetamine metabolites that may produce adverse effects and interfere with any putative disease-modifying effects. The oral disintegrating tablet formulation of selegiline allows pregastric absorption, minimizing first-pass metabolism, thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline, more potent than selegiline, exhibits disease-modifying effects in experimental models and lacks amphetamine metabolites. Both the symptomatic and potential disease-modifying effects of rasagiline are under investigation. A third agent with MAO-B inhibition properties, safinamide, is in phase III development. Although not yet approved, safinamide may offer the added advantage of combined MAO-B and dopamine reuptake inhibition.

Haq IU, Lewitt PA, Fernandez HH. · Movement Disorders Program, University of Florida, Department of Neurology/McKnight Brain Institute, 100 S. Newell Drive, PO Box 100236, Gainesville, Florida 32610-0236, USA. · Expert Opin Pharmacother. · Pubmed #17956200 No free full text.

Abstract: Motor fluctuations are common and distressing for patients with advanced Parkinson's disease. Subcutaneous apomorphine injections can be an extremely valuable adjunctive therapy. In this review, the authors discuss the history, pharmacology, efficacy, safety and proper administration of apomorphine for treating 'off' states in Parkinson's disease, with a focus on intermittent subcutaneous administration.

Mandel RJ, Burger C, Snyder RO. · Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA. · Exp Neurol. · Pubmed #17916354 links to  free full text

Abstract: Because Parkinson's disease is a progressive degenerative disorder that is mainly confined to the basal ganglia, gene transfer to deliver therapeutic molecules is an attractive treatment avenue. The present review focuses on direct in vivo gene transfer vectors that have been developed to a degree that they have been successfully used in animal model of Parkinson's disease. Accordingly, the properties of recombinant adenovirus, recombinant adeno-associated virus, herpes simplex virus, and lentivirus are described and contrasted. In order for viral vectors to be developed into clinical grade reagents, they must be manufactured and tested to precise regulatory standards. Indeed, clinical lots of viral vectors can be produced in compliance with current Good Manufacturing Practices (cGMPs) regulations using industry accepted manufacturing methodologies, manufacturing controls, and quality systems. The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration.

Rodriguez RL, Fernandez HH, Haq I, Okun MS. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, Florida, USA. · Neurologist. · Pubmed #17848865 No free full text.

Abstract: BACKGROUND: Deep brain stimulation (DBS) has emerged as an important treatment for medication refractory movement and neuropsychiatric disorders. General neurologists and even general practitioners may be called upon to screen potential candidates for DBS. The patient selection process plays an important role in this procedure. REVIEW SUMMARY: In this article, we discuss "pearls" for the clinician who may be called upon to identify appropriate candidates for DBS. Additionally, we will discuss the important points that should be considered when referring patients for surgical intervention. CONCLUSION: Diagnosis, response to levodopa, cognitive status, psychiatric status, access to care, and patient expectations are all essential elements of the patient selection process for DBS. These areas must be adequately addressed prior to any surgical procedure.

Edwards TM, Myers JP. · Department of Zoology, University of Florida, Gainesville, Florida 32611, USA. · Environ Health Perspect. · Pubmed #17805414 links to  free full text

Abstract: OBJECTIVE: Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. DATA SOURCES: We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. DATA SYNTHESIS: Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Mechanisms include regulation of gene translocation, histone modifications, DNA methylation, DNA repair, transcription, RNA stability, alternative RNA splicing, protein degradation, gene copy number, and transposon activation. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. One of the best-studied areas of gene regulation is epigenetics, especially DNA methylation. Our examples of environmentally induced changes in DNA methylation are presented in the context of early development, when methylation patterns are initially laid down. This approach highlights the potential role for altered DNA methylation in fetal origins of adult disease and inheritance of acquired genetic change. CONCLUSIONS: The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. Second, the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.

Zesiewicz TA, Sullivan KL, Hauser RA. · Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida 33612, USA. · Curr Neurol Neurosci Rep. · Pubmed #17618536 No free full text.

Abstract: Although levodopa is the gold standard for treating motor symptoms of Parkinson's disease (PD), long-term therapy leads to levodopa-induced dyskinesia (LID). Dyskinesia refers to involuntary movements other than tremor and most commonly consists of chorea that occurs when levodopa-derived dopamine is peaking in the brain ("peak-dose dyskinesia"). However, dyskinesia can also consist of dystonia or myoclonus and occur during other parts of the levodopa dosing cycle. New validated rating scales and home diaries can better help the health care provider assess the timing and severity of dyskinesia. The exact etiology of LID is unknown, but there is evidence that abnormal pulsatile stimulation of dopamine receptors may be contributory. Treatment of LID includes adjustment of PD medications to maximize "on" time without troublesome dyskinesia. Amantadine is the only medication available with demonstrated ability to reduce the expression of established LID without reducing antiparkinsonian benefit. Other medications that are currently being studied to treat established LID include antiepileptics and serotonergic medications. Deep brain stimulation of the subthalamic nucleus is now the most commonly used surgical procedure for PD patients, and it is very effective in treating LID.

Sudhyadhom A, Bova FJ, Foote KD, Rosado CA, Kirsch-Darrow L, Okun MS. · Department of Neurology, McKnight Brain Institute, 100 South Newell Drive, Gainesville, FL 32610, USA. · Curr Neurol Neurosci Rep. · Pubmed #17618533 No free full text.

Abstract: The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

Fernandez HH, Chen JJ. · Movement Disorders Center, Department of Neurology, McKnight Brain Institute/University of Florida, Gainesville, FL 32610, USA. · Clin Neuropharmacol. · Pubmed #17545750 No free full text.

Abstract: Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B results in elevation of synaptosomal dopamine concentrations. Data have been reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy as adjunctive treatment in levodopa-treated PD patients with motor fluctuations is equivocal. A new formulation of selegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa. The Zydis formulation allows pregastric absorption of selegiline, minimizing first-pass metabolism, and thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with at least 5 times the potency of selegiline in vitro and in animal models. Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients) as initial monotherapy in patients with early PD, and in 2 large, controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as adjunctive treatment in levodopa-treated PD patients with motor fluctuations. Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine metabolites. A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects.

Hauser RA, Zesiewicz TA. · Department of Neurology, Parkinson's Disease and Movement Disorders Center, University of South Florida and Tampa General Healthcare, Tampa, Florida 33606, USA. · Neurologist. · Pubmed #17495756 No free full text.

Abstract: BACKGROUND: Levodopa, in combination with a dopa decarboxylase inhibitor, provides the greatest symptomatic benefit with the fewest short-term side effects in the treatment of Parkinson disease (PD). However, the disease continues to progress, and the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesias. REVIEW SUMMARY: Alternatives to the use of levodopa in early PD include monoamine oxidase B (MAO-B) inhibitors, dopamine agonists, and amantadine. Although no medication has been proven to slow the progression of Parkinson disease, preclinical studies have demonstrated neuroprotective effects of MAO-B inhibitors, and a recent study of rasagiline found that PD patients treated with rasagiline for 12 months experienced less progression of symptoms than patients treated with placebo for 6 months followed by rasagiline for 6 months. Several clinical trials have demonstrated that the initial use of a dopamine agonist to which levodopa can be added is associated with fewer motor complications than treatment with levodopa alone. In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. CONCLUSION: Treatment of early PD with an MAO-B inhibitor, dopamine agonist, or amantadine, may provide useful alternatives to treatment with levodopa. Adding entacapone at the initiation of levodopa therapy may reduce the development of motor complications. Long-term studies are required to evaluate the potential long-term benefits of these treatment strategies.

Okun MS, Fernandez HH, Rodriguez RL, Foote KD. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, USA. · Geriatrics. · Pubmed #17489644 No free full text.

Abstract: Deep brain stimulation (DBS) can improve symptoms in well-selected patients with Parkinson's disease. Primary care physicians must take into account many important issues when considering referral for DBS. The Florida Surgical Questionnaire for PD (FLASQ-PD), a 5-section screening tool that can help primary care providers identify appropriate DBS candidates, can be filled out and scored by a general practitioner, advanced clinical nurse practitioner, physician assistant, or trained nurse. Potential candidates who score well on this questionnaire can be referred for presurgical multidisciplinary evaluation at an experienced DBS implanting center.

Halkias IA, Haq I, Huang Z, Fernandez HH. · Department of Neurology, University of Florida, Gainesville, Florida 32608, USA. · Drugs Aging. · Pubmed #17432922 No free full text.

Abstract: Levodopa is available in three forms: immediate-release, orally disintegrating and sustained-release tablets. Levodopa is metabolised in the gastrointestinal tract, kidney and liver by aromatic acid dopa decarboxylase using pyridoxine as a cofactor. Approximately 70-80% of the dose is eliminated in the urine. Central conversion of levodopa to dopamine likely occurs at surviving dopaminergic terminals and at serotonergic and adrenergic nerve terminals that contain decarboxylase. Dopamine is metabolised by catechol-O-methyltransferase and monoamine oxidase. The major metabolites of dopamine are homovanillic acid and dihydroxyphenylacetic acid.Levodopa remains the most efficacious pharmacological treatment for the symptoms of Parkinson's disease (PD). Results of current levodopa trials suggest that treatment with levodopa at the onset of disease provides superior motor and functional control compared with dopamine receptor agonists. Moreover, levodopa is generally better tolerated with a lower incidence of gastrointestinal and neuropsychiatric adverse effects. The debate over the role of levodopa in the treatment of PD is fuelled by the results of in vitro studies that show generation of free radicals by levodopa and its toxic effects on cell cultures. Levodopa has also consistently been shown to produce motor fluctuations (in particular dyskinesias) sooner than has been observed in PD patients, especially younger patients, given dopamine agonists initially. However, the cumulative body of knowledge thus far does not show definitive evidence that levodopa is neurotoxic to parkinsonian patients.In older PD patients with lesser risk of motor fluctuations, levodopa may be used initially, and perhaps solely, in demented PD patients and those at higher risk of developing neuropsychiatric adverse effects. In young parkinsonian patients with mild motor dysfunction, use of levodopa may be delayed or the dosage minimised. However, because of levodopa's superior efficacy, when a rapid and sustained symptomatic improvement is required because of significant motor disability, levodopa may be used as the first-line agent regardless of age.

Zesiewicz TA, Sullivan KL, Hauser RA. · Parkinson's Disease and Movement Disorders Center and Department of Neurology, University of South Florida,12901 Bruce B. Downs Blvd, MDC Box 55, Tampa, FL 33612, USA. · Expert Rev Neurother. · Pubmed #17181428 No free full text.

Abstract: Nonmotor symptoms occur commonly in Parkinson's disease (PD) patients and are frequently under-recognized and undertreated. Symptoms include sleep abnormalities, fatigue, autonomic disturbances, mood disorders and cognitive dysfunction. Early recognition and treatment of nonmotor symptoms in PD is critical to providing optimal management. A new screening questionnaire and the revised Unified PD Rating Scale should assist healthcare providers to better identify and evaluate these symptoms. This article reviews the identification and treatment of nonmotor symptoms in PD.

Sapienza CM, Wheeler K. · Department of Communication Sciences and Disorders, University of Florida, Gainesville, FL 32611, USA. · Semin Speech Lang. · Pubmed #17117350 No free full text.

Abstract: Respiratory muscle strength training is a paradigm that has been used for numerous years with a variety of populations including but not limited to spinal cord injury, chronic obstructive pulmonary disease, multiple sclerosis, Parkinson's disease, voice disordered, sedentary elderly, and healthy young. The respiratory muscle strength program discussed here is an expiratory muscle strength training and uses a pressure threshold device with a regimented treatment protocol. The primary purpose of the expiratory muscle strength training program is to promote strength in the expiratory muscles. The training protocol occurs five times per day, 5 days a week, and consists of ~15-20 minutes per day of training by the user at home. The device threshold is changed weekly by a clinician to maintain a threshold load of 75% of an individual's maximum expiratory pressure. The threshold setting of the device is always based on the individual's recorded maximum expiratory pressure generated into a digital pressure gauge. Results of 4 weeks of expiratory muscle strength training protocols indicate up to a 50% improvement for healthy subjects, those with multiple sclerosis, and those with spinal cord injury. The potential transfer of expiratory muscle strength to functional outcomes is discussed, as well as how strength-training paradigms may influence cortical plasticity.