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Biomedical subjects

Joseph Jankovic

Publications and source records attributed to Joseph Jankovic.

At least 55 records · Page 3Linked to original sources
PubMed2006

Treatment of advanced Parkinson's disease.

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.

Antiparkinson Agents↗
PubMed2006

Long-term evaluation of deep brain stimulation of the thalamus.

OBJECT: The effects of thalamic deep brain stimulation (DBS) on essential tremor (ET) and Parkinson disease (PD) have been well documented, but there is a paucity of long-term data. The aim of this study was to evaluate the long-term safety and efficacy of DBS of the ventralis intermedius nucleus (VIM) of the thalamus for PD and ET. METHODS: Thirty-eight of 45 patients enrolled at five sites completed a 5-year follow-up study. There were 26 patients with ET and 19 with PD undergoing 29 unilateral (18 ET/11 PD) and 16 bilateral (eight ET/eight PD) procedures. Patients with ET were evaluated using the Tremor Rating Scale, and patients with PD were evaluated using the Unified Parkinson's Disease Rating Scale. The mean age of patients with ET was 70.2 years and 66.3 years in patients with PD. Unilaterally implanted patients with ET had a 75% improvement of the targeted hand tremor; those with bilateral implants had a 65% improvement in the left hand and 86% in the right compared with baseline. Parkinsonian patients with unilateral implants had an 85% improvement in the targeted hand tremor and those with bilateral implants had a 100% improvement in the left hand and 90% improvement in the right. Common DBS-related adverse events in patients receiving unilateral implants were paresthesia (45%) and pain (41%), and in patients receiving implants bilaterally dysarthria (75%) and balance difficulties (56%) occurred. Device-related surgical revisions other than IPG replacements occurred in 12 (27%) of the 45 patients. CONCLUSIONS: Thalamic stimulation is safe and effective for the long-term management of essential and Parkinsonian tremors. Bilateral stimulation can cause dysarthria and incoordination and should be used cautiously.

Activities of Daily Living↗
PubMed2006

Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.

Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.

Alzheimer Disease↗
PubMed2006

An update on the treatment of Parkinson's disease.

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.

Antiparkinson Agents↗
PubMed2005

Valproic acid-mediated Hsp70 induction and anti-apoptotic neuroprotection in SH-SY5Y cells.

Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, has been reported to exert neuroprotection against a variety of insults. We now show that VPA attenuates rotenone (a potent complex I inhibitor)-induced apoptosis through the induction of heat shock protein 70, which may interact with apoptotic-protease-activating factor 1. Activation of p-Akt, p-Bcl-2, as well as p-Erk1/2 by VPA may be co-contributors to the protection.

Apoptosis↗
PubMed2005

Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y.

PTEN-induced kinase 1 (PINK1) is a recently identified gene, mutations of which cause levodopa-responsive parkinsonism. An over-expression of wild-type PINK1 protects neurons from stress-induced mitochondrial dysfunction and apoptosis. We studied the effects of PINK1 suppression using small interfering RNA (siRNA), which can inhibit PINK1 mRNA expression up to 87%, and decrease PINK1 protein up to 80% in human dopaminergic cell line SH-SY5Y. Incubation with PINK1 siRNA decreased SH-SY5Y cell viability and significantly increased MPP(+) or rotenone-induced cytotoxicity. Our results indicate that reduction in PINK1 expression can trigger apoptotic process that can be exacerbated by the presence of MPP(+) or rotenone. These findings support the hypothesis that PINK1 participates in the protection of dopaminergic neurons.

Amino Acid Sequence↗
PubMed2005

Camptocormia: pathogenesis, classification, and response to therapy.

Originally considered a psychogenic disorder, camptocormia, an abnormal posture with marked flexion of thoracolumbar spine that abates in the recumbent position, is becoming an increasingly recognized feature of parkinsonian and dystonic disorders. Prior reports were limited by sample size, short follow-up, and paucity of data on response to therapy. The authors reviewed 16 patients evaluated in their PD Center and Movement Disorders Clinic diagnosed with camptocormia. In addition to detailed neurologic assessment all patients were videotaped. The mean age was 64.9 +/- 17.4 years, mean age at onset of neurologic symptoms was 51.5 +/- 19.9 years, duration from onset of neurologic symptoms to development of camptocormia was 6.7 +/- 7.6 years, and the mean duration of camptocormia was 4.5 +/- 3.9 years. Of the 16 patients, 11 (68.8%) had Parkinson disease (PD); others had dystonia (n = 4) and Tourette syndrome (n = 1). Twelve patients received levodopa, with minimal or no improvement in the camptocormia. Nine patients received botulinum toxin type A injections into the rectus abdominus, with notable improvement in their camptocormia in four. One patient underwent bilateral subthalamic nucleus deep brain stimulation for PD, but there was no improvement in camptocormia. Based on this series and a thorough review of the literature of camptocormia, head drop, and bent spine syndrome, the authors propose etiologic classification of camptocormia and conclude that this heterogeneous disorder has multiple etiologies and variable response to systemic and local therapies.

Abdominal Muscles↗
PubMed2005

Searching for a relationship between manganese and welding and Parkinson's disease.

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.

Age of Onset↗
PubMed2005

Secondary tics and tourettism.

Motor and phonic tics are most frequently due to Tourette syndrome, but there are many other causes of tics. We analyzed data on 155 patients with tics and co-existent disorders (101M/54F; mean age 40.5 +/- 20.2 years). Fourteen (9.0%) patients had tics associated with an insult to the basal ganglia, such as head trauma (N = 4, 2.5%), stroke (N = 2, 1.2%), encephalitis (N = 3, 1.9%) and other causes. In addition, certain drugs, toxins, and post-infectious causes were associated with tics. Rarely, peripheral injury can cause movement disorders, including tics (N = 1, 0.6%). Pervasive developmental disorders, including Asperger's syndrome (N = 13, 8.3%), mental retardation (N = 4, 2.5%), autism (N = 3, 1.9%), and Savant's syndrome (N = 1, 0.6%), also may be associated with tics, as noted in 21 of the 155 patients (13.5%). Genetic and chromosomal disorders, such as Down's syndrome 5 (3.2%), neuroacanthocytosis (N = 2, 1.2%), and Huntington's disease (N = 1, 0.6%), were associated with tics in 16 patients (10.3%). We have also examined the co-existence of tics and other movement disorders such as dystonia (N = 31, 20.0%) and essential tremor (N = 17, 10.9%). Sixteen (10.3%) patients presented psychogenic tics, and one (0.6%) psychogenic tics and dystonia; conversely, Tourette syndrome preceded the onset of psychogenic dystonia (N = 1, 0.6%), and psychogenic tremor (N = 1, 0.6%) in two patients. Finally, 12 (7.7%) patients had tics in association with non-movement related neurological disorders, such as static encephalopathy (N = 2, 1.2%) and seizures (N = 3, 1.9%). To understand the physiopathology of tics and Tourette syndrome, it is important to recognize that these may be caused or associated with other disorders.

Adult↗
PubMed2005

Genetic analysis of parkin co-regulated gene (PACRG) in patients with early-onset parkinsonism.

Parkin co-regulated gene (PACRG) is a recently identified gene which is transcriptionally co-regulated with parkin gene (PRKN) by a shared bidirectional promoter. To determine whether early-onset parkinsonism (EOP) is associated with PACRG mutation, we screened 112 patients with EOP and found three nucleotide variants: (1) T>C transition in intron 2 (nt 87004; NT_007422), (2) C>T transition (L214L) in exon 6 (nt 585706; NT_007422), and (3) T>A substitution in intron 5 (nt 585630; NT_007422), located 18 bp upstream from exon 6. Since none of these variations appear to be pathogenically relevant, our results suggest that mutation of PACRG plays little or no role in the development of EOP.

Adult↗
PubMed2005

Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.

Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor.

Benzothiazoles↗
PubMed2005

Pleuropulmonary fibrosis after long-term treatment with the dopamine agonist pergolide for Parkinson Disease.

Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.

Aged↗
PubMed2005

Metoclopramide-induced tardive dyskinesia in an infant.

We describe a 1-year-old girl who developed orofaciolingual stereotypy at age 2 months after a 17-day treatment with metoclopramide for gastroesophageal reflux. The stereotypy, documented by sequential videos, persisted for at least 9 months after the drug was discontinued. This patient represents the first documented case of tardive dyskinesia in an infant. We also review previous reports of tardive dyskinesia in children.

Adolescent↗
PubMed2005

Long-term botulinum toxin efficacy, safety, and immunogenicity.

To determine the long-term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow-up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 +/- 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0-to-4 scale (0 = no effect; 4 = marked improvement) was 3.7 +/- 0.6 and the mean total duration of response was 15.4 +/- 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab-negative patients, 16 resumed responsiveness after dose adjustments and 2 persisted as nonrespondents. Except for 1 patient, the 4 Ab-positive and the 2 clinical nonresponders are being treated with BTX-B. This longest reported follow-up of BTX injections confirms the long-term efficacy and safety of this treatment.

Aged↗