Parkinson Disease: Jankovic J

Jankovic J. · No affiliation provided · Ann Neurol. · Pubmed #18383071 No free full text.

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Jankovic J. · No affiliation provided · J Neurol Sci. · Pubmed #16199057 No free full text.

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Jankovic J. · No affiliation provided · Arch Neurol. · Pubmed #15767498 links to  free full text

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Rye DB, Jankovic J. · No affiliation provided · Neurology. · Pubmed #11839829 No free full text.

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Jankovic J. · No affiliation provided · Arch Neurol. · Pubmed #11735770 links to  free full text

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Weidong Le, Shen Chen, Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Neuroscientist. · Pubmed #19008336 No free full text.

Abstract: Parkinson disease (PD) probably represents a syndrome of different disorders and origins converging into a relatively uniform neurodegenerative process. Although clinical-pathological studies have suggested that the presymptomatic phase of PD may be relatively short, perhaps less than a decade, the authors postulate that the pathogenic mechanisms may begin much earlier, possibly even in the prenatal period. Thus, some patients with PD may be born with a fewer than normal number of dopaminergic (and nondopaminergic) neurons as a result of genetic or other abnormalities sustained during the prenatal or perinatal period; as a result of normal age-related neuronal attrition, they eventually reach the critical threshold (60% or more) of neuronal loss needed for onset of PD to become clinically manifest. The authors review the emerging evidence that genetic disruption of normal development, coupled with subsequent environmental factors (the so called multiple-hit hypothesis), plays an important role in the etiopathogenesis of PD.

Jankovic J. · Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, Texas 77030-3498, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #18344392 No free full text.

Abstract: OBJECTIVE: Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. METHODS: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms". RESULTS: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. CONCLUSIONS: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Stamey W, Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Neurologist. · Pubmed #18332838 No free full text.

Abstract: OBJECTIVES: The primary aim of this article is to critically review the clinical features and comorbidities, epidemiology, pathophysiology, and treatment of impulse control disorder (ICD) associated with Parkinson disease (PD). METHODS: References for this review were identified by searches of PubMed from 1980 until January 2008 with the terms "Parkinson disease," "impulse control," "pathologic gambling,""hypersexuality," "levodopa," and "dopamine agonists." Articles were also identified through searches of the authors' own files. Only papers published in English were reviewed. RESULTS: Pathologic gambling has emerged as one of the most prominent ICDs, although hypersexuality, compulsive shopping and other manifestations of obsessive-compulsive disorder may also dominate PD-related behavioral manifestations. Affected patients may demonstrate a pattern of self-escalation of dopaminergic medication dosing which may lead to a state of dependency. CONCLUSIONS: Patients most commonly affected by ICD, such as pathologic gambling and hypersexuality, are males who develop PD at a younger age, and those with a previous history of mood disorder, alcohol abuse, or obsessive-compulsive disorder. Dopaminergic drugs, particularly dopamine agonists, play an important role in triggering these nonmotor symptoms.

Pan T, Kondo S, Le W, Jankovic J. · Parkinson's Disease Research Laboratory, Baylor College of Medicine, Houston, TX 77030, USA. · Brain. · Pubmed #18187492 links to  free full text

Abstract: The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of alpha-synuclein and the increase of intracellular concentrations of non-mutant alpha-synuclein have been associated with Parkinson's disease phenotype. The demonstration that alpha-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant alpha-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.

Jankovic J. · Parkinson's Disease and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA. · Lancet Neurol. · Pubmed #18093549 No free full text.

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Inzelberg R, Jankovic J. · Department of Neurology, Meir Hospital, Kfar Saba, Tchernikovsky Street, Israel. · Neurology. · Pubmed #17699801 No free full text.

Abstract: There is substantial evidence based on well designed epidemiologic studies for low cancer rates in patients with Parkinson disease (PD). This risk reduction cannot be attributed to the recognized low life-long incidence of smoking in patients with PD, as not only smoking-related cancers but also non-smoking-related ones are less common in PD. Whereas the risk for most cancers appears to be relatively low in patients with PD, breast cancer and melanomas occur more frequently in the PD population as compared with controls. The relationship between this peculiar pattern of cancer rates and PD might be related to the involvement of common genes in both diseases. Mutations in parkin gene, for example, have been reported in several types of cancer. Furthermore, genes involved in familial forms of PD appear to be abnormally expressed in cancers. Thus, parkin and PINK1 might be tumor suppressor genes, whereas DJ-1 is an oncogene. Cell survival signals may differ owing to mutated genes and represent two opposite extremes such as cell proliferation in cancer and cell death due to apoptosis in PD. Unraveling the link between PD and cancer may open a therapeutic window for both diseases.

Jankovic J, Stacy M. · Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas 77030, USA. · CNS Drugs. · Pubmed #17630819 No free full text.

Abstract: Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists.Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires monitoring for hepatotoxicity.Amantadine is a noncompetitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson's disease when given adjunctively with levodopa.Dopamine agonists, also used as initial and adjunctive therapy in Parkinson's disease, improve motor response and decrease 'off' time purportedly through direct stimulation of dopamine receptors. Current dopamine agonists include bromocriptine, pergolide, cabergoline, lisuride, apomorphine, pramipexole, ropinirole and rotigotine. Although effective, this class of medications can be associated with cardiovascular and psychiatric adverse effects that can limit their utility.All medications used to manage levodopa-associated motor complications in patients with Parkinson's disease have had differing degrees of success. Although head-to-head comparisons of drugs within classes are rare, some differences have emerged related to effects on motor fluctuations, dyskinesias and on/off times, as well as to adverse effects. When choosing a drug to treat levodopa-induced complications, it is important to consider the risks and benefits of the different classes and of the specific agents within each class, given the different efficacy and safety profiles of each.

Kenney C, Jankovic J. · Parkinson's disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, Texas 77030, USA. · Expert Opin Pharmacother. · Pubmed #17563266 No free full text.

Abstract: Dopamine agonists are effective in delaying levodopa-induced dyskinesia in early Parkinson's disease (PD) and reducing motor fluctuations in advanced PD. Rotigotine, a novel dopamine receptor agonist, improves motor function in both early and advanced PD using a transdermal route of administration. A smaller, but convincing body of data, supports its ability to ameliorate the symptoms of restless legs syndrome as well. The side-effect profile mimics other dopamine agonists, with the addition of application-site reactions, most of which are mild-to-moderate. Advantages over existing dopamine agonists include once-daily administration, absence of food interactions, maintenance of stable plasma levels and utility in patients with swallowing difficulties.

Sheffield JK, Jankovic J. · Department of Neurology, Baylor College of Medicine, Parkinson's Disease Center & Movement Disorders Clinic, 6550 Fannin, Suite 1801, Houston, TX 77030, USA. · Expert Rev Neurother. · Pubmed #17563247 No free full text.

Abstract: Botulinum toxins are an effective treatment modality for a growing number of neurologic conditions. Although there has been varied interest and success in their use, they have been studied for a variety of conditions associated with Parkinson's disease. Conditions reviewed in this paper include hand and jaw tremor, dystonia, blepharospasm and apraxia of eyelid opening, bruxism, camptocormia, freezing of gait, sialorrhea and constipation. We will make comments when applicable on our unique experience with botulinum toxin in these conditions. Other conditions associated with Parkinson's disease, which will not be reviewed here, but may benefit from botulinum toxin treatment include anterocollis (also known as dropped head syndrome), hyperhidrosis, seborrhea and overactive bladder.

Deng H, Le W, Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Brain. · Pubmed #17353225 links to  free full text

Abstract: Essential tremor (ET), the cause of which remains poorly understood, is one of the most common neurological disorders. While environmental agents have been proposed to play a role, genetic factors are believed to contribute to its onset. Thus far, three gene loci (ETM1 on 3q13, ETM2 on 2p24.1 and a locus on 6p23) have been identified in patients and families with the disorder. In addition, a Ser9Gly variant in the dopamine D3 receptor gene on 3q13 has been suggested to be a risk factor. Moreover, genetically deficient animal models express a phenotype that overlaps with some clinical characteristics of the human form of the illness. Further analyses of these genetic abnormalities may lead to the identification of causative mutations and a better understanding of the molecular mechanisms in this common movement disorder.

Tan EK, Jankovic J. · Department of Neurology, Singapore General Hospital. · Arch Neurol. · Pubmed #16966499 No free full text.

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Diamond A, Jankovic J. · Movement Disorder Clinic, Colorado Neurologic Institute, 701 East Hampden Ave. Suite 330 Englewood, CO 80113, USA. · Expert Rev Neurother. · Pubmed #16893346 No free full text.

Abstract: Parkinson's disease is a progressive neurological disorder characterized by tremor, bradykinesia, rigidity, gait and postural instability and a variety of nonmotor symptoms. While these and other motor signs typically improve with levodopa, the so-called axial signs, such as dysarthria, dysphagia, postural instability and freezing, and most nonmotor signs, such as depression, cognitive decline and dysautonomia, usually do not respond satisfactorily to levodopa. Furthermore, the use of levodopa may be limited by the development of motor fluctuations, dyskinesias and other adverse effects. This manuscript reviews the medical management of advanced Parkinson's disease, focusing on the treatment of motor fluctuations and dyskinesias and of nonmotor and nonlevodopa responsive symptoms.

Shahed J, Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, 6550 Fannin, Suite 1801, Houston, TX, USA. · Parkinsonism Relat Disord. · Pubmed #16887374 No free full text.

Abstract: Although essential tremor (ET) and Parkinson's disease (PD) are considered distinct disorders, there is overlap in some clinical features. In some PD patients, a long-standing postural tremor in the hands may precede the onset of parkinsonian features by several years or decades. Furthermore, large families with both ET and PD phenotypes have been described and autopsy studies have demonstrated Lewy body pathology in brains of ET patients. Functional neuroimaging suggests that some ET patients have dopaminergic deficit. We examine here the evidence for and against an association between ET and PD, and critically review data supporting the notion that a subset of ET patients is predisposed to developing PD.

Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, The Smith Tower, Suite 1801, 6550 Fannin, Houston, TX 77030, USA. · Mt Sinai J Med. · Pubmed #16878274 links to  free full text

Abstract: Although levodopa remains the most effective symptomatic drug for Parkinson's disease (PD), its use is limited by the emergence of motor fluctuations and dyskinesias, particularly in young-onset patients. Dopamine agonists, catechol-O-methyltransferasee inhibitors and other anti-parkinsonian drugs have been found to diminish or prevent these complications and possibly to exert disease-modifying effects. The finding that the subthalamic nucleus (STN) and the globus pallidum internus (GPi) are abnormally active in PD has led to effective surgical treatments designed to improve patients' quality of life. The relative benefits of targeting STN or GPi with high-frequency stimulation are still being debated. Experimental therapeutics of PD include novel delivery systems, anti-apoptotic strategies and implantation of genetically engineered cells, and stem cells. Despite encouraging results from early pre-clinical and clinical studies, trials of human fetal grafts and intraventricular and intraparenchymal infusion of glial cell-line-derived neurotrophic factor have not shown clinically meaningful benefits. Future therapeutic strategies should focus not only on ameliorating the symptoms of PD, but also on neuroprotective or neurorescue therapies that can favorably modify the natural course of the disease and slow the progression of both motor and nonmotor manifestations of PD.

Jankovic J, Chen S, Le WD. · Department of Neurology, Parkinson Disease Research Lab, Baylor College of Medicine, Houston, TX 77030, USA. · Prog Neurobiol. · Pubmed #16243425 No free full text.

Abstract: Nurr1, a transcription factor belonging to the orphan nuclear receptor superfamily, is critical in the development and maintenance of the dopaminergic system and as such it may have role in the pathogenesis of Parkinson' disease (PD). Human Nurr1 gene has been mapped to chromosome 2q22-23 and Nurr1 protein is predominantly expressed in central dopaminergic neurons. Nurr1 interacts with other factors critical for the survival of mensencephalic dopaminergic neurons and it appears to regulate the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and l-aromatic amino acid decarboxylase (AADC), all of which are important in the synthesis and storage of dopamine. Experimental studies in Nurr1 knock-out mice indicate that Nurr1 deficiency results in impaired dopaminergic function and increased vulnerability of those midbrain dopaminergic neurons that degenerate in PD. Decreased Nurr1 expression is found in the autopsied PD midbrains, particularly in neurons containing Lewy bodies, as well as in peripheral lymphocytes of patients with parkinsonian disorders. Several variants in Nurr1 gene have been reported in association with PD. All these studies suggest that Nurr1 is not only essential in the development of mensencephalic dopaminergic neurons and maintenance of their functions, but it may also play a role in the pathogenesis of PD.

Diamond A, Jankovic J. · Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 6550 Fannin Street, Suite 1801, Houston, TX 77030, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #16107348 links to  free full text

Abstract: Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Neurology. · Pubmed #15985567 No free full text.

Abstract: Research into the causes of Parkinson disease (PD) has accelerated recently with the discovery of novel gene mutations. The majority of PD cases, however, remain idiopathic and in those cases environmental causes should be considered. Several recent reports have focused on welding and manganese toxicity as potential risk factors for parkinsonism and some have even proposed that welding is a risk factor for PD. The controversy has stimulated this review, the primary aim of which is to critically and objectively examine the evidence or lack of evidence for a relationship among welding, manganese, parkinsonism, and PD.

Ashour R, Tintner R, Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Lancet Neurol. · Pubmed #15963445 No free full text.

Abstract: Striatal deformities of the hand and foot are abnormal postures that are common in patients with advanced Parkinson's disease (PD); they can present in the early stages of PD and in other parkinsonian disorders. Over a century ago, Charcot and Purves-Stewart recognised these deformities, which cause substantial functional disability and discomfort. The term striatal is used because pathology in the neostriatum (putamen and caudate) has been suggested to cause the deformities, but the pathogenesis is unknown. Misdiagnosis of the deformities is common-particularly when they occur early and in the absence of cardinal parkinsonian signs, such as tremor, bradykinesia, and rigidity-because the hand deformities are similar to those in rheumatoid arthritis, equinovarus foot deformity typically suggests an orthopaedic problem, and toe extension may be thought to be the Babinski sign of upper-motor-neuron syndromes. Here we review the background and clinical features of these deformities to highlight these commonly unrecognised and poorly understood parkinsonian signs.

Olanow CW, Jankovic J. · Department of Neurology, Mount Sinai School of Medicine, Annenberg 14-94, One Gustave L. Levy Place, New York, NY 10029, USA. · Mov Disord. · Pubmed #15822111 No free full text.

Abstract: The introduction of levodopa in the late 1960s represented a landmark in the therapy of Parkinson's disease (PD). However, motor complications of chronic levodopa therapy have emerged as a major limitation of this otherwise effective therapy. Advancing medical and surgical treatment of these complications has been the main objective of clinical trials during the past few decades. In addition, basic research has focused on better understanding of the mechanisms of motor complications and how to prevent them. Slowing or delaying the progression of the disease delays the need for levodopa therapy; therefore, neuroprotective strategies may play an important role in preventing the onset and reducing the severity of levodopa-related adverse effects. In this introductory review, we present the rationale for current and experimental therapies designed to favorably modify the progression of PD. If implemented early in the course of the disease, such treatments, if found effective, may not only alter the natural progression of the disease but may also delay or minimize motor and nonmotor complications associated with levodopa.

Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. · Mov Disord. · Pubmed #15822109 No free full text.

Abstract: Fluctuations in the symptoms of Parkinson's disease (PD), such as wearing-off and on-off effects, and dyskinesias are related to a variety of factors, including duration and dosage of levodopa, age at onset, stress, sleep, food intake, and other pharmacokinetic and pharmacodynamic mechanisms. The majority of patients, particularly those with young onset of PD, experience these levodopa-related adverse effects after a few years of treatment. Assessment of these motor complications is difficult because of the marked clinical variability between and within patients. Daily diaries have been used in clinical trials designed to assess the effects of various pharmacological and surgical interventions on motor fluctuations and dyskinesias. The most common type of dyskinesia, called "peak-dose dyskinesia", usually consists of stereotypical choreic or ballistic movements involving the head, trunk, and limbs, and occasionally, the respiratory muscles, whereas tremor and punding are less-common complications. Dystonia is also typically seen in patients with diphasic dyskinesia and wearing-off effect. Recognition of the full spectrum of clinical phenomenology of levodopa-related motor complications is essential for their treatment and prevention.