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Biomedical subjects

Joseph Jankovic

Publications and source records attributed to Joseph Jankovic.

At least 73 records · Page 4Linked to original sources
PubMed2005

Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study.

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.

Adult↗
PubMed2005

Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy.

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations.

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.

Adult↗
PubMed2005

Palatal myoclonus: an unusual presentation.

We describe a 16-year-old woman with an unusual clinical presentation of palatal myoclonus after a severe upper respiratory infection. Besides the postinfectious onset, this case is unique in that the rhythmical contractions of her oropharynx, larynx, and esophagus occur in couplets rather than single contractions of typical essential palatal myoclonus. Additionally, these contractions are present only during the inspiratory phase of respiration. Imaging and other diagnostic studies show no evidence of cerebellar or brainstem pathology. This case broadens the phenomenology of palatal myoclonus and illustrates the occasional overlap in clinical features between essential and symptomatic palatal myoclonus.

Adolescent↗
PubMed2005

Age-dependent dopaminergic dysfunction in Nurr1 knockout mice.

The Nurr1 gene, which codes for a transcriptional factor in the nuclear receptor superfamily, plays an important role in the development of the mesencephalic dopaminergic (DAergic) system. To study the age-dependent effects of Nurr1 expression in maintaining mature nigrostriatal DAergic neuronal function, we examined motor behaviors, determined nigrostriatal dopamine (DA) levels and the number of nigral DAergic neurons, and measured the expression of several DAergic neuron-associated genes in heterozygous Nurr1-deficient (Nurr1+/-) and wild-type mice of different ages. In contrast to the same-aged, wild-type mice, old Nurr1+/- mice (>15 months) had a significant decrease in both rotarod performance and locomotor activities, suggesting a motor impairment that is analogous to parkinsonian deficit. Furthermore, the abnormal motor behaviors in old Nurr1+/- mice were associated with decreased DA levels in the striatum, decreased number of DAergic neurons in the nigra, and reduced expression of Nurr1 and DA transporter in the nigra. Our data indicate that Nurr1 plays an important role in the functional maintenance and survival of nigral DAergic neurons and suggest that the Nurr1+/- mouse is a useful animal model to study the pathogenesis of Parkinson disease (PD) and to explore disease-modifying strategies.

Aging↗
PubMed2005

Striatal deformities of the hand and foot in Parkinson's disease.

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.

Animals↗
PubMed2005

Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice.

Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased expression of neuronal nitric oxide synthase and increased 3-nitrotyrosine were observed in striatum of Nurr1 heterozygous (Nurr1 +/-) mice as compared with wild-type. Increased cytochrome C activation and consecutive release of Smac/DIABLO were also observed in Nurr1 +/- mice. An induction of active Caspase-3 and p53, cleavage of poly-ADP (RNase) polymerase and reduced expression of bcl-2 were observed in Nurr1 +/- mice. Methamphetamine significantly increased these markers in Nurr1 +/- mice as compared with wild-type. The present data therefore suggest that nitric oxide plays a role as a modulating factor for the increased susceptibility, but not the potentiation, of the dopaminergic terminals in Nurr1 +/- mice. We also report that this increased neuronal nitric oxide synthase expression and increased nitration in Nurr1 +/- mice led to the activation of apoptotic cascade via the differential alterations in the DNA binding activity of transcription factors responsible for the propagation of growth arrest as well as apoptosis.

Animals↗
PubMed2005

Genetic mouse models of essential tremor: are they essential?

The causative genes for essential tremor (ET), one of the most common genetic neurological disorders, have eluded scientists despite intensive search. Two gene loci linked to ET, one on chromosome 3q13 and another on chromosome 2p24.1, have been identified, and a missense mutation in the HS1-BP3 gene on the 2p has been suggested as the cause of the disorder in about 10% of American ET patients. Therefore, the genetic basis for the vast majority of familial ET is still unknown. In this issue of the JCI, the gene coding for the gamma-aminobutyric acidA (GABA(A)) receptor alpha1 subunit is suggested as a potential candidate gene for ET, as mice lacking the gene express a phenotype that overlaps with some clinical characteristics of the human condition.

Animals↗
PubMed2005

Emerging drugs in Tourette syndrome.

Proper education of the patient is the first step in the treatment of Tourette syndrome (TS). Before deciding how to treat the patient, it is important to decide whether to treat the TS-related symptoms. Counselling and behavioural modification may be sufficient for those with mild symptoms. Medications, however, may be considered when symptoms begin to interfere with peer relationships, social interactions, academic or job performance, or with activities of daily living. Therapy must be individualised and the most troublesome symptoms should be targeted first. Antidopaminergic agents are clearly the most effective drugs in the treatment of tics. Although haloperidol and pimozide are the only drugs currently approved by the FDA for the treatment of TS, other dopamine receptor-blocking drugs and tetrabenazine, a dopamine depleting drug, as well as botulinum toxin injections, have been used to treat tics associated with TS. Carefully designed, comparative, longitudinal trials assessing the efficacy and adverse-effect profiles of these drugs, including tardive dyskinesia, are lacking. Selective serotonin reuptake inhibitors are recommended for the treatment of obsessive-compulsive behaviour: a common comorbidity. Psychostimulants, such as methylphenidate, are the treatment of choice for attention deficit hyperactivity disorder. Even though these drugs may transiently increase tics, this does not necessarily constitute a definite contraindication to the use of these drugs in patients with TS. Here, existing and emerging medical treatments in patients with tics and comorbid behavioural disorders associated with TS are reviewed.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Clinical application of botulinum toxin type B in movement disorders and autonomic symptoms.

OBJECTIVE: [corrected] To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sialorrhea and hyperhidrosis. METHODS: A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 +/- 0.8 years. Results of the first and last treatment of patients with at least 3 injection sessions were compared. RESULTS: The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response. The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection sessions (mean 10 +/- 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment. CONCLUSIONS: Though most patients require increased dosage to maintain effective response after repeated injections, BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.

Anti-Dyskinesia Agents↗
PubMed2004

Glabellar and palmomental reflexes in Parkinsonian disorders.

The authors examined the glabellar reflex and the palmomental reflex in 100 subjects, including patients with Parkinson disease (n = 41), patients with progressive supranuclear palsy (n = 12), patients with multiple system atrophy (n = 7), and healthy, age-matched, controls (n = 40). The study provides evidence that these reflexes, particularly glabellar reflex, are relatively sensitive signs of parkinsonian disorders, but they lack specificity as they do not differentiate among the three most common parkinsonian disorders.

Adult↗
PubMed2004

Clinical gait and balance scale (GABS): validation and utilization.

Gait and Balance Scale (GABS) consists of historical information and examination of 14 different gait and balance parameters designed to assess the severity of these functional domains. Thirty-five patients with Parkinson's disease (PD), Hoehn and Yahr stages 1-3, were tested during their "off" period. GABS items were compared to quantitative data from two computerized gait analysis instruments, GAITRite and Pro Balance Master. Intra-class correlation coefficients were calculated to establish reliability. Intra-rater test-retest reliability was determined using Cohen's Kappa statistic. Concurrent validity was derived using the Spearman's rho test with the items from GABS, GAITRite and Balance Master. Intra-rater reliability was high with k>0.41 (k=kappa statistic) for 17 items, 6 had k>0.61. When performing validity measurements, a number of items on the GABS had a correlation coefficient significant at p<0.01 (2-tailed). Posture, pull test, balance during stance, single limb stance, tandem stance, turning, toe walking and functional reach had significant correlation with Balance Master data (R=0.46-1). Gait, arm swing, gait speed, steps/5 m, 'up-and-go test', modified performance oriented assessment of gait scale and provocative testing had significant correlation with the GAITRite items (R=0.51-0.83). GABS is an easy-to-use comprehensive clinical scale with high intra-rater and internal item reliability. We have shown concurrent validity with two computerized gait analysis instruments. We expect GABS to have a particular utility in clinical trials designed to modify functional impairment associated with abnormalities in gait and balance.

Aged↗
PubMed2004

Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Aged↗
PubMed2004

Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration.

Hallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3-p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase-associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 (PANK2) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult-onset patients whereas dystonia seems more frequent in the earlier-onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome.

Adolescent↗
PubMed2004

Minocycline in Huntington's disease: a pilot study.

Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase (iNOS), and has been shown to delay disease progression in the mouse model R6/2 of Huntington's disease (HD). This safety and tolerability study included 30 patients with HD who were given minocycline over a 6-month period and underwent assessments every 2 months with laboratory studies, the Abnormal Involuntary Movements Scale, the Unified Huntington's Disease Rating Scale, and the Mini-Mental State Examination. Minocycline was well tolerated during this study period and no serious adverse events were noted.

Adult↗