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Biomedical subjects

Joseph Jankovic

Publications and source records attributed to Joseph Jankovic.

At least 91 records · Page 5Linked to original sources
PubMed2004

Treatment of cervical dystonia with botulinum toxin.

Cervical dystonia (CD) is the most common form of dystonia encountered in a movement disorders clinic. The treatment of this focal dystonia has improved markedly with the advent on botulinum toxin (BTX) injections, which has now become the treatment of choice. Initial studies, even double-blind controlled trials, failed to show robust effect, largely as a result of poor design, often using fixed dosage and site of administration. When the BTX treatment is customized to the needs of the individual patients and the most involved muscles are targeted, the effects can be quite dramatic and the improvement usually lasts 3 to 4 months. Experience and improved skills can largely prevent the adverse effects such as dysphagia and neck weakness. Although there is no evidence that BTX slows the progression of the disease, as a result of early intervention with BTX, many of the long-term complications of CD, such as contractures and radiculopathy, have been largely eliminated.

Anti-Dyskinesia Agents↗
PubMed2004

Atypical parkinsonism and motor neuron syndrome in a Biosphere 2 participant: a possible complication of chronic hypoxia and carbon monoxide toxicity?

Exogenous toxins and chronic hypoxia have been implicated in the etiopathogenesis of a variety of neurological disorders, but it is not always possible to establish a cause-effect relationships. We describe a patient who presented with an unusual gait disorder and progressive motor neuron disease after residing for 2 years within Biosphere 2, a scientifically engineered dome, tightly sealed to allow miniscule exchange of air between its atmosphere and the earth's atmosphere. We postulate that this unusual syndrome resulted from chronic hypoxia possibly coupled with carbon monoxide and nitrous oxide exposure.

Aged↗
PubMed2004

Examination of the SGCE gene in Tourette syndrome patients with obsessive-compulsive disorder.

Mutations in the epsilon-sarcoglycan gene (SGCE) have been reported in families with myoclonus-dystonia (M-D). In addition to abnormal movements, obsessive-compulsive disorder (OCD) has also been described in families with M-D. OCD is a common feature in another movement disorder, namely Tourette syndrome (TS). The comorbidity of these disorders suggests that common genetic factors might be involved in their susceptibility. To evaluate this, we performed two sets of experiments. An association study using a polymorphism within an intron of the SGCE gene was assessed in patients with TS and OCD versus controls, and the SGCE gene itself was screened for mutations in all TS/OCD patients, followed by direct sequencing of the gene in a limited number of these patients. No correlation was found by either method.

Adolescent↗
PubMed2004

Neurodegenerative disease and iron storage in the brain.

PURPOSE OF REVIEW: Iron is very important for normal regulation of various metabolic pathways. Neurons store iron in the form of ferrous ion or neuromelanin. In specific disorders the axonal transport of iron is impaired, leading to iron deposition which in the presence of reactive oxygen species results in neurodegeneration. RECENT FINDINGS: Recent developments in genetics, including the finding of mutations in the pantothenate kinase gene and ferritin light chain gene, have demonstrated a direct relationship between the presence of a mutation in the iron-regulatory pathways and iron deposition in the brain resulting in neurodegeneration. These two disorders now add to our understanding of the mechanism of disease due to dysfunction of iron-regulatory pathways. In addition to these disorders there may be several other mutations of iron-regulatory genes or related genes that are yet to be found. The animal models of disease have also added value to this area. SUMMARY: In this review we provide a summary of recent developments in the field of movement disorders with abnormalities in iron transport, and the current evidence in neurodegenerative disorders such as Parkinson's disease.

Animals↗
PubMed2004

Safety of botulinum toxin type A: a systematic review and meta-analysis.

OBJECTIVE: To define quantitatively the safety and tolerability profile of botulinum toxin type A (BTX-A) across all common therapeutic indications. The review was limited to the evaluation of the safety profile of one preparation of BTX-A (BOTOX) because distinct formulations of BTX-A are associated with different clinical profiles, requiring separate consideration for an analysis of safety. RESEARCH DESIGN AND METHODS: We identified randomized controlled trials of BTX-A through searches of the MEDLINE, EMBASE, and Cochrane Controlled Trial databases for the years 1966-2003. Studies were double-blind, randomized, crossover, or of parallel group design. The search strategy included the terms 'botulinum toxin', 'therapeutic use', 'randomized controlled trial', 'controlled clinical trial', 'randomized clinical trial', and 'placebo controlled trial'. Only randomized controlled trials of at least 7 days duration that reported adverse events were included in the analysis. MAIN OUTCOME MEASURE: Safety was assessed by means of a meta-analysis of the number and frequency of adverse events. RESULTS: Thirty-six studies involving 2309 subjects met the inclusion criteria. These reported on 1425 subjects receiving BTX-A treatment. No study reported any severe adverse events. The meta-analysis of any mild to moderate adverse events showed a rate of roughly 25% in the BTX-A-treated group (353/1425 patients) compared with 15% in the control group (133/884 patients, p < 0.001). Focal weakness was the only adverse event that occurred significantly more often with BTX-A treatment than control. CONCLUSION: The results of this meta-analysis and experience from long-term, open-label investigations demonstrate that the formulation of BTX-A evaluated here has a favorable safety and tolerability profile across a broad spectrum of therapeutic uses.

Botulinum Toxins, Type A↗
PubMed2004

Essential tremor among children.

OBJECTIVE: To characterize the clinical and therapeutic aspects of essential tremor (ET) among children. BACKGROUND: ET, an autosomal dominant disorder, has been studied extensively among adults, but little is known regarding its occurrence, clinical characteristics, treatment, and prognosis in pediatric populations. Often stigmatized as a disorder of the elderly, ET may be misdiagnosed among children. Previous studies of childhood-onset ET were limited by small sample sizes. METHODS: Clinical data, including gender, age at onset, family history, associated disorders, and response to treatment, were collected for consecutive patients diagnosed with childhood-onset ET at the Movement Disorders Clinic at Baylor College of Medicine. RESULTS: Of the 39 patients with ET, 29 (74.4%) were male. The mean age at onset was 8.8 +/- 5.0 years, and the mean age at evaluation was 20.3 +/- 14.4 years. A family history of tremor was noted for 79.5% of the patients. Eighteen (46.2%) had some neurologic comorbidity, such as dystonia, which was noted for 11 patients (28.2%). Only 24 of the patients (61.5%) were treated with a specific antitremor medication; 5 of the 12 patients treated with propranolol experienced improvement. CONCLUSIONS: Concomitant movement disorders, such as dystonia, are common among patients with childhood-onset ET, which supports the concept that ET is a heterogeneous disorder. Treatment strategies used for adult patients with ET seem to be effective also for children with ET, although controlled therapeutic trials in this population of patients with ET are lacking.

Adolescent↗
PubMed2004

Psychogenic movement disorders: diagnosis and management.

Psychogenic movement disorders (PMDs) are best defined as hyper- or hypo-kinetic movement disorders, often associated with gait disorders, that cannot be directly attributed to a lesion or dysfunction of the nervous system and which are derived in most cases from psychological or psychiatric causes. There are a variety of PMDs including tremor, dystonia, parkinsonism, gait disorders and, even, unusual forms including paroxysmal dyskinesias. As has been recognised in the recent literature, PMDs cannot be strictly classified into clearly defined psychiatric disorders such as somatoform, dissociative or conversion disorders. In this review, we discuss the diagnosis of various PMDs (including hyper- and hypo-kinetic disorders; and current evidence for underlying comorbid disorders) and the current therapeutic approach to them. The therapy of PMDs is not well established, is very challenging to the clinician, and a better outcome can be achieved in the setting of a team approach involving movement disorders specialists, psychiatrists and therapists who specialise in cognitive-behavioural techniques. Current pharmacological and non-pharmacological approaches to treatment focus on therapy of underlying comorbid psychiatric and psychological issues, although compliance is a major concern.

Anxiety↗
PubMed2003

Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.

We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.

Age of Onset↗
PubMed2003

Neuroprotection in Parkinson disease.

Treatment of Parkinson disease has improved dramatically over the past quarter of a century and promising therapies are emerging. Although treatment with levodopa results in marked symptomatic improvement, mortality rates of the disease have remained relatively unchanged. Recent findings of abnormal protein folding, coupled with oxidative stress, provide scientific rationale for novel therapeutic strategies designed to slow disease progression. To be effective, these disease-modifying and neuroprotective therapies must be instituted early in the course of the disease and early diagnosis therefore is critical. Consequently, primary care physicians will play an increasingly important role in early institution of such neuroprotective strategies. This review is designed to highlight some of the recent advances in our understanding of the mechanisms of neurodegeneration and to draw attention to the importance of early recognition and implementation of the new therapeutic interventions.

Cell Death↗
PubMed2003

Haplotype analysis of the ETM2 locus in familial essential tremor.

The objective of this study was to analyze a sample of unrelated individuals with autosomal dominant essential tremor (ET) for a genetic association with loci in a candidate region (ETM2) on chromosome 2p24.1 that harbors a disease gene for ET. ET is a common movement disorder that is genetically linked to ETM2 in four large families. It is unknown whether this candidate locus is associated with dominantly inherited ET in other individuals. Based on information from previous genetic linkage studies, a linkage disequilibrium study was designed to compare individuals with a family history of ET (n=45) with normal controls (n=70). Three unreported dinucleotide polymorphic loci (etm1240, etm1231, and etm1234) were identified on a physical map of the ETM2 interval in a region of no recombination. The study sample was tested for allele frequency differences by the CLUMP program and haplotypes were analyzed by the FASTEHPLUS program. The allele frequencies were significantly different between ET cases and the control samples for the loci etm1231 (P< or =0.0419) and etm1234 (P<0.0001). A haplotype formed by the loci etm1231 and etm1234 occurred with a frequency of 29% in cases (n=45) and 9% in a white newborn sample (P<0.0001, n=35). The haplotype was not found in normal individuals older than 60 years without tremor (P=0.0063, n=35). This study provides evidence that an ancestral haplotype on chromosome 2p24.1 segregates with the ET disease phenotype in individuals with a family history of the disorder and will facilitate the search for a causative gene.

Aged↗
PubMed2003

A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia.

Mitochondrial DNA (mtDNA) mutations can cause rare forms of dystonia, but the role of mtDNA mutations in other types of dystonia is not well understood. We now report identification by sequencing, restriction endonuclease analyses, and clonal analyses of a heteroplasmic missense A to G base pair substitution at nucleotide position 3796 (A3796G) in the gene encoding the ND1 subunit of mitochondrial complex I in a patient with adult-onset dystonia, spasticity, and core-type myopathy. The mutation converts a highly conserved threonine to an alanine. The same mutation subsequently was identified in 2 of 74 additional unrelated adult-onset dystonia patients. A muscle biopsy was obtained from 1 of these 2 subjects and this revealed abnormalities of electron transport chain (ETC) activities. The mutation was absent in 64 subjects with early onset dystonia, 82 normal controls, and 65 subjects with Parkinson's disease or multiple system atrophy. The A3796G mutation previously has been reported in 3 of 226 subjects from mitochondrial haplogroup H. Each of the 3 subjects in our study harboring the A3796G mutation was also from haplogroup H. However, a subgroup analysis of haplogroup H subjects from our study indicates that the A3796G mutation is significantly overrepresented among haplogroup H adult-onset dystonia subjects compared with haplogroup H controls (P<0.01). This difference remains significant even after excluding the index patient (P=0.04). These data suggest that, among haplogroup H subjects, the presence of the A3796G mutation increases the risk of developing adult-onset dystonia.

Adolescent↗
PubMed2003

Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.

Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.

DNA, Mitochondrial↗
PubMed2003

Effects of green tea polyphenols on dopamine uptake and on MPP+ -induced dopamine neuron injury.

As antioxidants, polyphenols are considered to be potentially useful in preventing chronic diseases in man, including Parkinson's disease (PD), a disease involving dopamine (DA) neurons. Our studies have demonstrated that polyphenols extracted from green tea (GT) can inhibit the uptake of 3H-dopamine (3H-DA) and 1-methyl-4-phenylpyridinium (MPP(+)) by DA transporters (DAT) and partially protect embryonic rat mesencephalic dopaminergic (DAergic) neurons from MPP(+)-induced injury. The inhibitory effects of GT polyphenols on 3H-DA uptake were determined in DAT-pCDNA3-transfected Chinese Hamster Ovary (DAT-CHO) cells and in striatal synaptosomes of C57BL/6 mice in vitro and in vivo. The inhibitory effects on 3H-MPP(+) uptake were determined in primary cultures of embryonic rat mesencephalic DAergic cells. Inhibition of uptake for both 3H-DA and 3H-MPP(+) was dose-dependent in the presence of polyphenols. Incubation with 50 microM MPP(+) resulted in a significant loss of tyrosine-hydroxylase (TH)-positive cells in the primary embryonic mesencephalic cultures, while pretreatment with polyphenols (10 to 30 microg/ml) or mazindol (10 microM), a classical DAT inhibitor, significantly attenuated MPP(+)-induced loss of TH-positive cells. These results suggest that GT polyphenols have inhibitory effects on DAT, through which they block MPP(+) uptake and protect DAergic neurons against MPP(+)-induced injury.

1-Methyl-4-phenylpyridinium↗
PubMed2003

Movement disorders in Friedreich's ataxia.

Since the discovery of the gene mutation causing Friedreich's ataxia (FA), the rich spectrum of clinical manifestations of this autosomal recessive disorder is being increasingly recognized. Movement disorders besides ataxia, however, have not been fully characterized in patients with FA. We describe here two young male patients who, in addition to progressive ataxia, kinetic tremor and other typical features of FA, also manifest axial and limb dystonia. The primary purpose of this report is to draw attention to the broad spectrum of hyperkinetic movement disorders that can present as or be associated with FA.

Adolescent↗
PubMed2003

Migraine headache in patients with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is recognized as one of the most common childhood movement disorders, characterized by motor and phonic tics often associated with neurobehavioral comorbidities, such as obsessive-compulsive disorder. Neurotransmitter dysregulation, particularly involving the serotonin system, has been implicated in the pathogenesis of TS, obsessive-compulsive disorder, and migraine headache. OBJECTIVES: To investigate the possible association between migraine headache and TS and to report preliminary findings of family history of migraine headache in patients with TS. METHODS: Subjects diagnosed as having TS at the Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic were administered a migraine headache questionnaire based on the migraine criteria established by the Headache Classification Committee of the International Headache Society. RESULTS: Of 100 patients with TS, 25 (25.0%) satisfied the diagnostic criteria for migraine headache, significantly greater than the estimated 10% to 13% in the general adult population (P<.001) and the estimated 2% to 10% in the general pediatric population (P<.04). There was no significant (P =.44) difference in the presence of comorbid obsessive-compulsive traits in the TS migraine and TS nonmigraine sample groups. Furthermore, our TS group with migraines was not more likely to have features of obsessive-compulsive disorder compared with attention-deficit/hyperactivity disorder. Of patients with TS, 56.0% reported a family history of migraines, 44.0% of whom were first-degree relatives. CONCLUSIONS: The frequency of migraine headache in a clinic sample of TS subjects was nearly 4-fold more than the frequency of migraines reported in the general population. Contrary to previous reports, the co-occurrence of migraines and TS in our sample group may possibly be attributed to another TS comorbidity, other than obsessive-compulsive traits.

Adolescent↗