Biomedical subjects

J Jankovic

Publications and source records attributed to J Jankovic.

At least 37 records · Page 2Linked to original sources

PubMed2004

Haplotype analysis at the ETM2 locus in a Singaporean sample with familial essential tremor.

An ancestral haplotype on chromosome 2p24.1 described in an American sample with familial essential tremor (ET) was analyzed in a different ethnic sample from Singapore. Six polymorphic loci (etm1240, etm1231, etm1234, APOB, etm1241, and etm1242) in a 274-kb interval within an ET gene candidate region (ETM2) were analyzed in Singaporean individuals with a family history of ET (n = 52) and compared to Singaporean controls older than age 65 (n = 49). The allele frequencies were significantly different between cases and controls for the loci etm1234 (p = 0.0001) and APOB (p = 0.0320). An extended haplotype formed by the loci etm1231, etm1234, and APOB occurred with a frequency of 31% in Singaporean cases and in 1.8% of elderly Singaporean controls (p = 0.0005). Haplotype studies in two different population samples suggest that a disease locus for ET lies near or within the 100-kb interval between the loci etm1231 and APOB.

Adolescent↗

PubMed2004

Botulinum toxin in clinical practice.

Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications.

Autonomic Nervous System Diseases↗

PubMed2003

Vagus nerve stimulation for essential tremor: a pilot efficacy and safety trial.

OBJECTIVE: To assess the safety and efficacy of vagus nerve stimulation (VNS) for essential tremor (ET). METHODS: This was a pilot open-treatment trial at three centers, with masked videotape tremor assessments. Inclusion required a severity score of 3 or 4 on the Tremor Rating Scale (TRS) in one or both hands. At baseline, tremor was assessed with TRS and Unified Tremor Rating Assessment (UTRA), accelerometry, and a videotape protocol. The VNS device was implanted with leads placed around the left cervical vagus nerve. Stimulation was adjusted over 4 weeks before the repeat tremor assessments. Two raters masked to the study visit scored the videotapes. RESULTS: Nine subjects participated, with a mean age of 65 years and a mean age at onset of tremor of 24. Investigators rated hand tremor as mildly improved (TRS 2.3 +/- 0.7 during VNS vs 3.0 +/- 0.4 during baseline, p = 0.06). Accelerometry-measured total power improved 50.2 +/- 31.8% (p < 0.01). Videotape tremor scores were highly correlated between the masked raters and revealed no changes in tremor scores with treatment. VNS was well tolerated, with the most common adverse events being stimulation related. CONCLUSIONS: VNS was judged by investigators to mildly improve upper extremity tremor. This finding was not confirmed in videotape scoring by masked raters. VNS is not likely to have a clinically meaningful effect on ET.

Adolescent↗

PubMed2003

Hearing impairment in essential tremor.

OBJECTIVE: To assess hearing in patients with essential tremor (ET) vs patients with Parkinson disease (PD) and normal controls. METHODS: The authors assessed demographic and clinical information including use of hearing aids in 250 patients with ET, 127 patients with PD, and 127 normal controls. The authors administered the Nursing Home Hearing Handicap Index (NHHI), a validated measure of hearing disability. Regression techniques were used to adjust for factors such as age and sex. The authors assessed a complete audiologic evaluation in a subset of patients with ET. RESULTS: Patients with ET had worse adjusted NHHI scores when compared to patients with PD (p < 0.001), controls (p < 0.001), and both (p < 0.001). A higher percentage of patients with ET also used hearing aids (p < 0.0001). In the ET group, hearing loss was associated with tremor severity (p = 0.02) and tended to be associated with older age (p = 0.06), male sex (p = 0.06), and the absence of dystonia (p = 0.18). Audiology testing was consistent with high-frequency sensorineural hearing loss. Central processing was not disproportionally greater than peripheral loss. CONCLUSION: Patients with ET have increased hearing disability compared to patients with PD and normal controls, which correlates with tremor severity.

Aged↗

PubMed2003

Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia.

The authors compared 130 patients treated for cervical dystonia with original botulinum toxin (BTX) type A (Botox; Allergan, Inc., Irvine, CA), 42 of whom were exposed only to the original BTX type A used before 1998 (25 ng protein/100 units), and 119 treated only with the current BTX type A (5 ng of protein/100 units). Blocking antibodies were detected in 4 of 42 (9.5%) patients treated only with original BTX type A but in none of the 119 patients treated exclusively with current BTX type A (p < 0.004). The current preparation decreased the risk of antibody formation by a factor of six. The authors conclude that the low risk of antibody formation after current BTX type A treatment is related to lower protein load.

Age Distribution↗

PubMed2003

Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease.

Recently, the authors demonstrated linkage in idiopathic PD to a region on chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The authors examined NAT1 and NAT2 for association with PD using family-based association methods and single nucleotide polymorphisms (SNPs). The authors did not find evidence for association with increased risk for PD between any individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580 individuals).

Aged↗

PubMed2003

Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD.

OBJECTIVE: To assess the safety, tolerability, and biological activity of glial cell line-derived neurotrophic factor (GDNF) administered by an implanted intracerebroventricular (ICV) catheter and access port in advanced PD. BACKGROUND: GDNF is a peptide that promotes survival of dopamine neurons. It improved 6-OHDA- or MPTP-induced behavioral deficits in rodents and monkeys. METHODS: A multicenter, randomized, double-blind, placebo-controlled, sequential cohort study compared the effects of monthly ICV administration of placebo and 25, 75, 150, 300, and 500 to 4,000 microg of GDNF in 50 subjects with PD for 8 months. An open-label study extended exposure up to an additional 20 months and maximum single doses of up to 4,000 microg in 16 subjects. Laboratory testing, adverse events (AE), and Unified Parkinson's Disease Rating Scale (UPDRS) scoring were obtained at 1- to 4-week intervals throughout the studies. RESULTS: Twelve subjects received placebo and seven or eight subjects were assigned to each of the other GDNF dose groups. "On" and "off" total and motor UPDRS scores were not improved by GDNF at any dose. Nausea, anorexia, and vomiting were common hours to several days after injections of GDNF. Weight loss occurred in the majority of subjects receiving 75 microg or larger doses of GDNF. Paresthesias, often described as electric shocks (Lhermitte sign), were common in GDNF-treated subjects, were not dose related, and resolved on discontinuation of GDNF. Asymptomatic hyponatremia occurred in over half of subjects receiving 75 microg or larger doses of GDNF; it was symptomatic in several subjects. The open-label extension study had similar AE and lack of therapeutic efficacy. CONCLUSIONS: GDNF administered by ICV injection is biologically active as evidenced by the spectrum of AE encountered in this study. GDNF did not improve parkinsonism, possibly because GDNF did not reach the target tissues--putamen and substantia nigra.

Adult↗

PubMed2003

Paroxysmal kinesigenic dyskinesias.

The paroxysmal dyskinesias (PxDs) are involuntary, intermittent movement disorders manifested by dystonia, chorea, athetosis, ballismus or any combination of these hyperkinetic disorders. Paroxysmal kinesigenic dyskinesia (PKD), one of the four main types of PxD, involves sudden attacks of dyskinesias induced by voluntary movements. PKD most commonly occurs sporadically or as an autosomal-dominant familial trait with variable penetrance. Many causes of secondary PKD are being recognized. The exact pathophysiology of the PxDs awaits further elucidation, although basal ganglia dysfunction appears to play a major role. Although the precise gene remains unknown, genetic linkage studies have isolated loci on chromosome 16, which colocalizes with the locus for familial infantile convulsions and paroxysmal choreoathetosis in some studies. The episodic nature of PKD and its relationship with other episodic diseases, such as epilepsy, migraine, and episodic ataxia, suggests channelopathy as a possible underlying etiology. PKD may remit spontaneously, but it also responds well to anticonvulsants as well as some other agents.

Child↗

PubMed2002

Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease.

OBJECTIVE: To determine whether the Nurr1 gene, which is critical for the development and maintenance of nigral dopaminergic neurons, is a risk factor associated with PD. BACKGROUND: The Nurrl gene is highly expressed in the dopaminergic neurons in the midbrain. Knockout of the gene results in agenesis of nigral dopaminergic neurons and heterozygous knockout mice increases 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. METHODS: This study included 105 patients with familial PD (fPD) and 120 patients with sporadic PD (sPD) and 221 age-matched healthy control subjects. The polymorphisms and mutations of the Nurr1 gene in patients with PD were initially examined by heteroduplex analysis and sequencing analysis from PCR-amplified Nurr1 gene fragments. A polymorphism in the BseRI restriction site was identified, and a relatively large-scale analysis then was conducted by three independent investigators who were blinded to the clinical status of the subjects. RESULTS: A homozygous 7048G7049 polymorphism was found in intron 6 of the Nurr1 gene, which was significantly higher in fPD (10/105; 9.5%) and in sPD (5/120; 4.2%) compared with healthy control subjects (2/221; 0.9%). The mean age and the SD at onset of these homozygote patients with PD was 52 +/- 15 years for fPD and 46 +/- 7 years for sPD. The clinical features of these homozygote patients with PD did not differ from those of typical PD. CONCLUSIONS: The homozygote polymorphism of 7048G7049 in intron 6 of the Nurr1 gene is associated with typical PD.

Adult↗

PubMed2002

A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease.

BACKGROUND: To the extent that excitotoxicity may play a role in the pathogenesis of certain neurodegenerative disorders, antagonists of glutamate, an excitatory neurotransmitter, should exert neuroprotective effects in these disorders, including Parkinson's disease (PD). METHODS: Patients in early stages of PD, not previously treated with levodopa, were randomized to receive riluzole 50mg capsules orally, taken twice daily or a matching placebo. All subjects were evaluated at baseline (pre-treatment), at 1, 3 and 6 months (post-treatment), and following a 6-week washout. After the washout, all subjects were offered an enrollment in an open label, 1-year, extension study. The principal investigator (JJ), however, remained blinded to the original assignment during the entire study. The patients were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hoehn & Yahr (HY) stage, and Schwab and England (SE) ADL scale. The quantitative assessments included Movement Time (MT) and Reaction Time (RT). Additionally, the time to initiate dopaminergic therapy was assessed. Safety was determined at each visit by clinical history and examination, a panel of blood safety laboratory tests including complete blood count, chemistry profile, and liver function studies. RESULTS: Twenty patients with a mean age of 62+/-9.02 (range: 46-73) years and mean duration of symptoms of 18+/-9.53 (range: 6-36) months were enrolled. One patient withdrew from the study because he needed more aggressive treatment of his symptoms. Analysis of the efficacy variables showed no meaningful symptomatic effect of riluzole on UPDRS score. Likewise, there was no significant change in the median HY stage, SE ADL rating, or the MT/RT. Seventeen patients (mean age 62+/-9.26) elected to continue in the open label extension study. Although the observed deterioration in UPDRS scores seemed to be more pronounced in the placebo group than in the riluzole group, the difference did not reach statistical significance. There was no statistically significant difference in the latency between enrollment and start of symptomatic therapy when patients initially treated with riluzole were compared to those initially treated with placebo (8.3 vs 9 months). CONCLUSIONS: This pilot and extension study showed that riluzole, 100mg/day, was well tolerated in patients with early PD. No evidence of symptomatic effect of riluzole was observed. Because of the exploratory nature of the design and small size of the study, it was not possible to determine whether riluzole affected the natural history of PD. The encouraging results from our study, however, suggest that larger, longitudinal studies are warranted.

Aged↗

PubMed2002

Methods of H-reflex evaluation in the early stages of Parkinson's disease.

Differentiating the early stages of Parkinson's disease from the normal consequences of aging or from other common neurologic conditions can be diagnostically problematic. The purpose of this study was to compare methodologies for measuring motor neuron excitability of Parkinson's disease patients with a control group. H-reflexes were monitored in 16 patients diagnosed in the early stages of Parkinson's disease (Hoehn & Yahr stages I and II) compared with 30 subjects who were disease free. Methods of measurement included H-reflex latencies, the relative values of maximum H-reflexes to maximum direct motor responses (H-to-M ratio), the relative values of H-reflex amplitudes during vibration compared with control H-reflex amplitudes (Hv-to-Hc ratio), and double-stimulation H-reflex recovery curves using different interstimulus interval parameters. No significant differences were observed for the H-to-M or Hv-to-Hc ratios, or for the H-reflex latencies. The H-reflex recovery curves for the patients with Parkinson's disease demonstrated significantly greater ratio amplitudes than the control group during the double-stimulus responses between the 150-msec and 700-msec interstimulus intervals. Although comparisons of simple H-reflexes and H-reflexes during vibration did not differentiate the patients in the early stages of Parkinson's disease from the control group, the double-stimulation paradigm was a sensitive method for detecting early diagnoses of this disease.

Adult↗

PubMed2001

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

Adult↗

PubMed2001

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Age of Onset↗

PubMed2001

Daytime sleepiness and other sleep disorders in Parkinson's disease.

BACKGROUND: PD is associated with a variety of sleep problems. The dopamine agonists (DA) pramipexole and ropinirole were recently implicated in causing "sleep attacks" and motor vehicle accidents. METHODS: In order to determine the overall rate of subjective sleep problems in PD and to determine if any factors, including specific medications, correlate with sleep pathology, the authors surveyed consecutive patients with PD seen over a 3-month period in a Movement Disorders Clinic. The authors collected demographic and medication data, and the patients completed the Epworth Sleepiness Scale (ESS), questions assessing the presence of restless legs syndrome (RLS), a modified National Sleep Foundation sleep survey, and specific questions regarding falling asleep while driving. RESULTS: A total of 320 patients completed the questionnaire. The authors eliminated 17, six for incomplete data and 11 for having a primary diagnosis other than PD. The mean age of the remaining 303 patients was 67.1 +/- 10.7 years, and the mean duration of PD was 9.1 +/- 5.7 years. The ESS scores averaged 11.1 +/- 5.9, and in 50.2% of patients the score was abnormally high (>10). Stepwise regression analysis found that sleepiness correlated with longer duration of PD (p < 0.001), more advanced PD (p < 0.004), male sex (p < 0.001), and the use of any DA (p < 0.003). The soporific effects of the three most common DA (pramipexole, ropinirole, and pergolide) were similar. Falling asleep while driving was reported by 63/279 (22.6%) of current drivers and correlated with higher ESS scores (p < 0.05). Other sleep disorders, including RLS, were also frequently reported. CONCLUSION: Daytime sleepiness is common in PD and correlates with more advanced and longer duration of PD, and male sex. The DA were also independently associated with daytime sleepiness, but in this group, no single DA was more culpable than the others.

Adult↗

PubMed2001

Tourette's syndrome.

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Adrenergic alpha-Agonists↗

PubMed2001

Freezing of gait in PD: prospective assessment in the DATATOP cohort.

OBJECTIVE: To study the development of freezing of gait in PD. BACKGROUND: Freezing of gait is a common, disabling, and poorly understood symptom in PD. METHODS: The authors analyzed data from 800 patients with early PD from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) clinical trial who were assigned either placebo, deprenyl, tocopherol, or the combination of deprenyl and tocopherol. The primary outcome measure was the time from randomization until the freezing of gait score on the Unified Parkinson's Disease Rating Scale (UPDRS) became positive. RESULTS: Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect. CONCLUSIONS: Freezing of gait is directly related to duration of PD. Risk factors at onset of disease are the absence of tremor and PD beginning as a gait disorder. The development of freezing of gait in the course of the illness is strongly associated with the development of balance and speech problems, less so with the worsening of bradykinesia, and is not associated with the progression of rigidity. These results support the concept that the freezing phenomenon is distinct from bradykinesia. Deprenyl, in the absence of L-dopa, was found to be an effective prophylactic treatment and should be considered for patients with PD who have an onset of gait difficulty.

Aged↗

PubMed2001

Alcohol dehydrogenase polymorphism and Parkinson's disease.

A particular alcohol dehydrogenase (ADH) polymorphism (allele A1) in the promoter region of the gene has been recently demonstrated to be associated with increased risk of Parkinson's disease (PD). In a case control study, we examine frequencies of ADH A1 allele in 100 PD patients (i.e. 200 alleles), 100 diseased controls (i.e. 200 alleles), and 194 healthy controls (i.e. 388 alleles). In addition, we study possible association of a combined non-amyloid component of plaque (NACP-Rep 1) allele and ADH A1 allele with risk of PD. There was no statistical significance of the frequencies of ADH A1 allele between PD patients 12/200 (6%), diseased controls 13/200 (6.5%), and healthy controls 20/388 (5.2%). No strong evidence of an association was found between ADH A1 allele and PD susceptibility in our study patients. There was also no suggestion of linkage disequilibrium between NACP-Rep 1 and ADH A1 alleles.

Adult↗

PubMed2001

Functional decline in Parkinson disease.

OBJECTIVES: To determine the overall rate of functional decline and to assess the progression of different signs of Parkinson disease (PD). PATIENTS AND METHODS: Patients with clinically diagnosed PD followed up for at least 3 years were included in this study. Demographic and clinical data (including the Unified Parkinson's Disease Rating Scale [UPDRS]) were analyzed by the multivariate unbalanced repeated-measurements design using the mixed-effects model to study the association between different symptoms and various demographic variables. Regression models helped estimate the rates of progression of the disease in relationship to the various components of the UPDRS. Patients were categorized as having tremor-dominant or postural instability-gait difficulty-dominant PD and the 2 categories were compared for progression of their total UPDRS scores. DESIGN: A multivariate mixed-effects model was used to study the relationship between the different symptoms and various demographic variables. Nonparametric statistical tests were used to compare the progression of symptoms in the "on" (good function) state and the "off" (poor function) state groups for 2 age-at-onset categories (< or =57 and >57 years). RESULTS: Data from 1731 visits on 297 patients (181 men) followed up for an average of 6.36 years (range, 3-17 years) were analyzed. The annual rate of decline in the total UPDRS scores was 1.34 when assessed during the on state and 1.58 when assessed during the off state. Patients with an older age at onset had more rapid progression of PD than those with a younger age at onset. Furthermore, the older-onset group had statistically significantly more progression in mentation, freezing, and parts I (mentation) and II (activities of daily living) UPDRS subscores. Handwriting was the only component of the UPDRS score that did not notably deteriorate during the observation period. Regression analysis of 108 patients whose symptoms were rated during their off state showed a faster rate of cognitive decline as age at onset increased. The slopes (ie, the annual rates of decline) of progression in the UPDRS scores, when adjusted for age at the initial visit, were steeper for the postural instability--gait difficulty--dominant group compared with the tremor-dominant group. CONCLUSION: Based on longitudinal follow-up data, our findings provide evidence for a variable course of progression of the different PD symptoms, thus implying different biochemical or degenerative mechanisms for the various clinical features associated with PD.

Adolescent↗