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J Jankovic

Publications and source records attributed to J Jankovic.

At least 73 records · Page 4Linked to original sources
PubMed2001

Botulinum toxin for the treatment of cervical dystonia.

Cervical dystonia (CD) manifests clinically through involuntary spasms of neck muscles, producing abnormal head and neck movements and postures, which is often associated with pain. CD is the most common form of focal dystonia presenting to movement disorders clinics. Chemodenervation with botulinum toxin (BTX) has become the first-line treatment for CD, producing satisfactory relief of symptoms in > 80% of cases. Unresolved issues that may impact on the overall results include the method of selection for injection sites (clinical vs. electromyography), dosing, dilution and the role and relative efficacy of the different BTX serotypes. A guiding therapeutic principle of BTX injections is to achieve optimal results with the lowest possible dosage and frequency of administration. This strategy is critical in order to keep the risk of immunoresistance at a minimum. Development of antibodies that block the effects of BTX, usually associated with frequent injections of high doses, is the main reason for secondary unresponsiveness to this treatment. Although the mechanism of denervation at the neuromuscular junction by BTX is relatively well understood, the role of changes in muscle spindles and myopathic pain mechanisms, as well as secondary changes at the level of the basal ganglia, thalamus and cortex and their role in response to BTX, all need further exploration.

Anti-Dyskinesia Agents↗
PubMed2001

Are dopamine receptor agonists neuroprotective in Parkinson's disease?

Dopamine receptor agonists are playing an increasingly important role in the treatment of not only patients with advanced Parkinson's disease and those with levodopa-induced motor fluctuations, but also in the early treatment of the disease. This shift has been largely due to the demonstrated levodopa-sparing effect of dopamine agonists and their putative neuroprotective effect, with evidence for the latter being based largely on experimental in vitro and in vivo studies. In this article we review the evidence for neuroprotection by the dopamine agonists pramipexole, ropinirole, pergolide, bromocriptine and apomorphine in cell cultures and animal models of injury to the substantia nigra. Most of the studies suggest that dopamine agonists may have neuroprotective effects via direct scavenging of free radicals or increasing the activities of radical-scavenging enzymes, and enhancing neurotrophic activity. However, the finding that pramipexole can normalise mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells derived from mitochondrial DNA of patients with nonfamilial Alzheimer's disease suggests an even broader implication for the neuroprotective role of dopamine agonists. Although the clinical evidence for neuroprotection by dopamine agonists is still limited, the preliminary results from several ongoing clinical trials are promising. Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progression of Parkinson's disease using various surrogate markers of neuronal degeneration such as 18F-levodopa positron emission tomography and 123I beta-CIT (carbomethoxy-beta-4-iodophenyl-nortropane) single positron emission computed tomography. The results of these experimental and clinical studies will improve our understanding of the action of dopamine agonists and provide critical information needed for planning future therapeutic strategies for Parkinson's disease and related neurodegenerative disorders.

Animals↗
PubMed2001

Parkinson's disease therapy: treatment of early and late disease.

PURPOSE: To summarize the current strategies for the treatment of early and late Parkinson's disease (PD). DATA SOURCES: The presented guidelines are based on the review of the literature as well as the author's extensive experience with the treatment of 7000 patients with PD over the past 25 years. RESULTS: An analysis of reported data as well as personal experience suggest that while young patients seem to have a slower progression of the disease, they are at a higher risk for developing levodopa induced complications, such as motor fluctuations and dyskinesias. It is, therefore, prudent practice to delay levodopa therapy, particularly in younger patients, until the PD symptoms become troublesome and interfere with social or occupational functioning. Other strategies, such as the use of deprenyl, amantadine, trihexphenidyl and dopamine agonists, should be employed before instituting levodopa therapy. Entacopone and dopamine agonists are useful in smoothing out levodopa related motor fluctuations. Surgical interventions, such as pallidotomy and pallidal or subthalamic deep brain stimulation, are effective therapeutic strategies, but should be reserved only for patients in whom optimal medical therapy fails to provide satisfactory control of symptoms. CONCLUSION: The medical and surgical treatment of patients with PD must be individualized and tailored to the needs of the individual patient.

Antiparkinson Agents↗
PubMed2000

An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy.

OBJECTIVE: To confirm the association of an extended 5'-tau haplotype on chromosome 17q with the disease phenotype in clinically ascertained individuals with sporadic progressive supranuclear palsy (PSP). BACKGROUND: PSP is a neurodegenerative disease with parkinsonian signs accompanied by vertical supranuclear palsy and tau pathologic features. Previously, we documented the complete segregation of an extended 5'-tau haplotype consisting of four single nucleotide polymorphisms (SNP) with the disease phenotype in sporadic PSP. This study was conducted in an independent cohort to confirm these results and to improve the statistical power of the data. DESIGN AND METHODS: Direct sequencing and restriction enzyme digests were used to analyze four SNP in tau Exons 1, 4A, and 8. These contiguous SNP were used to reconstruct an extended 5'-tau haplotype in 52 affected and 54 age-matched control individuals. RESULTS: The four SNP formed two homozygous 5'-tau haplotypes (HapA and HapC) or a heterozygous genotype. Fifty-one (98%) patients with PSP had HapA; one (2%) with a later onset was heterozygous; and none had HapC. These PSP haplotype frequencies were different (p < 0.00001) from those of the age-matched control group, in which 18 (33%) people had HapA; 26 (48%) were heterozygous; and 10 (19%) had HapC. The extended 5'-tau haplotype, HapA, had a high sensitivity (98%) and a moderate specificity (67%) as a marker for PSP. CONCLUSIONS: A 5'-tau susceptibility haplotype may be a sensitive marker for sporadic PSP and a genetic defect in, or closely linked to, tau may contribute to the cause of PSP.

Chromosomes, Human, Pair 17↗
PubMed2000

Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson's disease.

The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p <0.001). Improvements in parkinsonian symptoms were maintained in both"off" and "on" states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).

Adult↗
PubMed2000

The pharmacokinetic and clinical effects of tolcapone on a single dose of sublingual apomorphine in Parkinson's disease.

Apomorphine (APO) is a potent dopamine agonist that is partially metabolized by catachol-O-methyl transferase (COMT). Tolcapone was the first COMT inhibitor available for use as adjunctive therapy to levodopa in Parkinson's disease (PD). In order to determine whether this compound might increase the serum area under the curve (AUC) of APO and whether this results in any clinical benefit, we administered 200mg doses of tolcapone to five fluctuating PD patients taking an investigational sublingual APO preparation. Serial tapping speed and gait speed were assessed at 15min intervals over four hours, in conjunction with APO serum levels, following a single dose of APO, both before and five days after starting tolcapone (600mg/day). Serum APO levels tended to be higher (12.6%), and clinical measures suggested improvement during the APO "on" period after the addition of tolcapone (22.5% improvement in gait speed, and 7.6% improvement in tapping speed), but neither reached statistical significance. Further trials, involving larger samples are needed to clearly establish the pharmacokinetic and clinical effect of tolcapone in PD patients taking APO.

Journal Article↗
PubMed2000

Variability and validity of polymorphism association studies in Parkinson's disease.

BACKGROUND: In recent years, interest in gene-environment interactions has spurred a great number of association studies on polymorphism of different genes. OBJECTIVE: To review case-control studies of genetic polymorphisms in PD, and perform meta-analysis of individual gene polymorphism. METHODS: The authors searched the Medline database (PubMed) for publications (English language) from January 1966 to November 1999 for association studies in PD. The key words used were "PD" and "polymorphism." The authors supplemented the search with relevant references quoted in these published articles. Those with four or more independent studies of a specific gene polymorphism were subjected to meta-analysis, with the exception of cytochrome-P450 enzyme polymorphisms, for which meta-analyses results were already available in the literature. RESULTS: The authors identified 84 studies on 14 genes, including dopamine receptors (DRD2 and DRD4), dopamine transporter (DAT), monoamine oxidase (MAOA and MAOB), catechol-O-methyltransferase (COMT), N-acetyltransferase 2 (NAT2), APOE, glutathione transferase (GSTT1, GSTM1, GSTP1, and GSTZ1), and mitochondrial genes (tRNAGlu and ND2). Four polymorphisms showed significant association with PD: slow acetylator genotypes of NAT2 (PD:control OR = 1.36), allele >188bp of the MAOB (GT)n polymorphism (OR = 2.58), the deletion allele of GSTT1 (OR = 1.34), and A4336G of tRNAGlu (OR = 3.0). No significant differences were found for the other genes. CONCLUSION: Significant associations with PD were found in polymorphisms of NAT2, MAOB, GSTT1, and tRNAGlu. Although significant association does not imply a causal relationship between the presence of the polymorphisms and PD pathogenesis, their pathophysiologic significance should be studied further.

Apolipoproteins E↗
PubMed2000

Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies.

OBJECTIVE: To clinically characterize affected individuals in families with paroxysmal kinesigenic dyskinesia (PKD), examine the association with infantile convulsions, and confirm linkage to a pericentromeric chromosome 16 locus. BACKGROUND: PKD is characterized by frequent, recurrent attacks of involuntary movement or posturing in response to sudden movement, stress, or excitement. Recently, an autosomal dominant PKD locus on chromosome 16 was identified. METHODS: The authors studied 11 previously unreported families of diverse ethnic background with PKD with or without infantile convulsions and performed linkage analysis with markers spanning the chromosome 16 locus. Detailed clinical questionnaires and interviews were conducted with affected and unaffected family members. RESULTS: Clinical characterization and sampling of 95 individuals in 11 families revealed 44 individuals with paroxysmal dyskinesia, infantile convulsions, or both. Infantile convulsions were surprisingly common, occurring in 9 of 11 families. In only two individuals did generalized seizures occur in later childhood or adulthood. The authors defined a 26-cM region using linkage data in 11 families (maximum lod score 6.63 at theta = 0). Affected individuals in one family showed no evidence for a shared haplotype in this region, implying locus heterogeneity. CONCLUSIONS: Identification and characterization of the PKD/infantile convulsions gene will provide new insight into the pathophysiology of this disorder, which spans the phenotypic spectrum between epilepsy and movement disorder.

Adolescent↗
PubMed2000

Polymorphism of NACP-Rep1 in Parkinson's disease: an etiologic link with essential tremor?

An allele (263bp) of the nonamyloid component of plaques (NACP)-Repl polymorphism has shown association with sporadic PD in a German population. The authors studied this polymorphism in 100 American PD patients and 100 healthy controls. The authors also studied 46 essential tremor (ET) and 55 Huntington's disease (HD) patients. Allele 263bp was significantly higher in PD patients (OR = 3.86) and ET patients (OR = 6.42) but not HD patients, compared with healthy controls. The association of allele 263bp with PD and ET suggests a possible etiologic link between these two conditions.

Adult↗
PubMed2000

Pramipexole inhibits lipid peroxidation and reduces injury in the substantia nigra induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 mice.

Pramipexole has been showed to protect cultured dopaminergic (DAergic) cells against free radical-induced cytotoxicity. To test if pramipexole is protective against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-mediated nigral DAergic injury in vivo and if such protection is related to inhibition of lipid peroxidation, DAergic function and lipid peroxidation were determined in MPTP-treated C57BL/6 mice. We reported that MPTP administration induced a 38.1% increase of lipid peroxidation product thiobarbituric acid reactive substance (TBARS) in nigra, a 46.7% decrease of tyrosine hydroxylase -positive nigral DAergic neurons and a 59.4% reduction of striatal DA levels. However, pramipexole treatment significantly inhibited the TBARS production by 76%, and attenuated the MPTP-induced decreases in nigral DAergic neurons and striatal DA levels by about 50%. This study suggests that pramipexole can inhibit free radical-mediated lipid peroxidation and protect MPTP-induced nigral injury.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Computerized posturography analysis of progressive supranuclear palsy: a case-control comparison with Parkinson's disease and healthy controls.

BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is frequently mistaken for Parkinson's disease (PD) in its early stages. OBJECTIVE: To compare balance measures using computerized posturography in patients with early PSP and early PD. METHODS: We performed computerized posturography (SMART Balance Master; NeuroCom International, Inc, Clackamas, Ore) in 20 patients with clinically diagnosed mild to moderate PSP (ambulatory) and compared results with those from 20 patients with PD of similar age and disease duration who were not receiving medications, and from 20 healthy age- and sex-matched controls. Sensory organization testing (SOT), limits of stability (LOS), and toes-up perturbations (4 degrees at 50 degrees per second) were tested while receiving and not receiving a combination of oral carbidopa (25 mg) and levodopa (250 mg) in the PSP group. Clinical assessment included Unified Parkinson's Disease Rating Scale, Performance-oriented assessments, and functional reach. RESULTS: When compared with the PD and control groups, total LOS time (P < .001) and path sway (P < .001) were significantly prolonged in PSP. Total SOT showed significantly worse scores in PSP compared with PD and control groups (F(2,57) = 29.6; P < .001). Univariate follow-up tests comparing PSP and PD showed differences in the following conditions: eyes open and visual sway (P = .003), eyes open and platform sway (P = .003), eyes closed and platform sway (P < .001), and eyes open and platform and visual sway (P < .001). Medium- and long-latency responses to perturbation were similar, but a larger number in the PSP group lacked short-latency responses (chi(2) = 11.3; P = .002). Levodopa administration did not significantly improve any aspect of posturography testing in PSP. In differentiating PSP from PD, LOS time and SOT condition of eyes open and platform and visual sway were nearly 100% sensitive and 100% specific (canonical correlation, 0.91). CONCLUSIONS: Computerized posturography testing reliably differentiated early PSP from early PD and age-matched controls. The PSP group demonstrated severely contracted limits of stability with probable deficits in motor programming. Results of SOT in PSP suggested a vestibular pattern and overreliance on visual cues, even when incorrect. The absence of short-latency responses (monosynaptic reflex arch) suggests an additional disturbance in the spinal cord or peripheral nervous system. Arch Neurol. 2000;57:1464-1469

Aged↗
PubMed2000

The evolution of diagnosis in early Parkinson disease. Parkinson Study Group.

CONTEXT: Since there is no diagnostic biological marker for Parkinson disease (PD), the diagnosis is based on the results of clinical assessment. The accuracy of diagnosis improves with time and repeated assessments. Studies that require only inclusion of early cases of PD present a diagnostic challenge. Previous studies concluded that initial diagnoses of PD made by general neurologists were incorrect in 24% to 35% of the cases when patients were examined at autopsy. Experts in movement disorders are expected to have greater accuracy of initial diagnosis of PD. OBJECTIVE: To determine the evolution of clinical diagnosis in patients with early PD made initially by experts in PD. DESIGN: Eight hundred patients with mild parkinsonian symptoms (Hoehn and Yahr stage 1 or 2) who received a diagnosis of PD less than 5 years before the beginning of the study were included in the original Deprenyl and Tocopherol Antioxidative Therapy for Parkinson's Disease study. These patients were followed up prospectively with repeated clinical assessments. The following clinical criteria were used to reassess the initial diagnosis: investigator's confidence in the diagnosis of PD, presence of atypical clinical features, findings of imaging studies, response to levodopa, and results of autopsy examinations. RESULTS: The mean +/- SD duration of illness in the 800 cases at enrollment was 2.2+/-1.3 years, and the mean +/- SD Hoehn and Yahr stage was 1.6+/-0.5. The mean +/- SD follow-up was 6.0+/-1.4 years (range, 0.2-7.6 years). In 5 cases, PD was not confirmed at autopsy, and in 15 patients, the results of imaging studies indicated the presence of other pathological conditions. Of the 550 cases treated with levodopa, 49 (8.9%) had little or no improvement; 6 of these cases overlap with either autopsy or imaging study exclusion criteria. Two other cases had at least 4 of the 6 atypical clinical features arguing against the diagnosis of PD. Thus, of the 800 patients, 65 (8.1%) did not have PD according to the study criteria. Compared with those patients with the final diagnosis of PD, in the diagnoses of 60 patients without autopsy, the duration of symptoms (mean +/- SD, 7.2+/-2.0 years vs. 8.3+/-1.9 years; P<.001) and the duration of follow-up (5.3+/-1.6 years vs. 6.1+/-1.3 years; P<.001) were shorter. CONCLUSIONS: We found that 65 (8.1%) of patients initially diagnosed as having PD were later found to have an alternate diagnosis based on multifactorial clinical diagnostic criteria. This alternate diagnosis indicated that experts in PD changed their diagnoses infrequently during the 7.6-year follow-up.

Age of Onset↗