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M Stacy

Publications and source records attributed to M Stacy.

At least 19 recordsLinked to original sources
PubMed2006

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia.

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.

Botulinum Toxins↗
PubMed2006

Development of a Patient Questionnaire to facilitate recognition of motor and non-motor wearing-off in Parkinson's disease.

We previously reported that the use of a specifically designed Wearing-Off Questionnaire (WOQ) identified symptoms of wearing-off more frequently than standard assessments conducted by movement disorder specialists during a routine office visit. In the previous study we used a WOQ of 32 symptoms; however this tool was not designed for daily use. In this paper we describe the retrospective development of a simpler, 19-symptom WOQ more suitable for routine clinical use.

Aged↗
PubMed2005

Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.

Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of the probands are affected approximately 4 times as frequently as relatives of control subjects. Several genes have been implicated as genetic risk factors for PD. We investigated the presence of six reported genetic variations in the SCNA, NR4A2, and DJ-1 genes in 292 cases of familial Parkinson's disease from the GenePD study. None of the variants were found in the GenePD families. Our results suggest that other variants or genes account for the familial risk of PD within the GenePD study.

Aged↗
PubMed2003

A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study.

OBJECTIVE: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. METHODS: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. RESULTS: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). CONCLUSIONS: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

Adolescent↗
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↗
PubMed2002

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

Age of Onset↗
PubMed2001

Genome-wide scan for Parkinson's disease: the GenePD Study.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.

Aged↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2000

Pharmacotherapy for advanced Parkinson's disease.

Medical management of Parkinson's disease consists of two strategies. A presynaptic strategy attempts to maintain physiologic synaptic concentrations of dopamine, usually by individualizing delivery of levodopa (or exogenous dopamine) by varying the rate of gastrointestinal absorption or blood-brain barrier passage. A postsynaptic strategy bypasses degenerating nigrostriatal neurons by stimulating striatal neurons directly with dopamine agonists. With advancing disease, motor fluctuations appear, related to physiologic changes that narrow the window of levodopa concentration in which symptoms are under control. Then it becomes necessary to add dopamine agonists to therapy.

Antiparkinson Agents↗
PubMed2000

Idiopathic cervical dystonia: an overview.

Idiopathic cervical dystonia (CD) is the most common of the adult-onset focal dystonias. It manifests as involuntary muscle contractions that cause twisting or turning of the neck. The resulting abnormal head and neck postures are heterogeneous in their presentation. Because of the variable presentation of the disease and the poor recognition of its clinical spectrum of manifestations, CD is frequently misdiagnosed and accurate diagnosis of the disease is commonly delayed. The pathogenesis of CD remains obscure. However, genetic factors, trauma, the sensory system, and impaired basal ganglia function may all play a role in the development of this disease.

Dystonia↗
PubMed1999

Managing late complications of Parkinson's disease.

Treatment of parkinsonism becomes more difficult as the disease progresses, and results from increasing neuronal degeneration, side effects from antiparkinsonian medications, or most often, a combination of each. Neurodegenerative parkinson symptoms may result from substantia nigra destruction, or from other areas in the nervous system. These include the cortex (cognitive and psychiatric disorders), brainstem (bulbar abnormalities), intermediolateral cell column (autonomic disturbances), among others. Medication side effects produce motor fluctuations, dyskinesias, delirium, hallucinations, psychosis, orthostatic hypotension, sleep disorders, and a host of other well-recognized complications. This article is divided into sections concerning motor fluctuations, gait difficulty bulbar disturbances, autonomic disturbances, sleep disorders, cognitive disorders, and psychiatric disorders, and is an attempt to provide the reader with strategies for treating common complications in the advanced Parkinson's disease patient.

Cognition Disorders↗
PubMed1999

Parkinson's disease: therapeutic choices and timing decisions in patient management. Interview by Wayne Kuznar.

Parkinson's disease is a progressive neurodegenerative disorder characterized by striatal dopaminergic loss. Carbidopa/levodopa is the most effective drug treatment for disease management. It reduces bradykinesia and rigidity, but is less effective against tremor. Whether carbidopa/levodopa should be used at the time of initial diagnosis or delayed until symptoms become disabling is controversial. A clinical trial is in progress to help resolve this dilemma. As carbidopa/levodopa loses efficacy with continued use, adjunct therapies using catechol-O-methyl-transferase inhibitors or dopamine agonists may be considered. In younger patients exhibiting parkinsonian symptoms, dopamine agonists may be used as first-line therapy. A new, reversible surgical intervention known as deep-brain stimulator placement is being used to control disabling tremor in patients not responding to optimal drug therapy.

Age Factors↗
PubMed1998

Respiratory function in Parkinson's disease.

This article reviews the spectrum of respiratory dysfunction in Parkinson's disease (PD). It includes the primary effects of PD on the ventilation, response to medications, and pulmonary complications of antiparkinson therapy. Primary pulmonary abnormalities include a restrictive change mainly secondary to chest wall rigidity and upper airway obstruction; both are responsive to dopaminergic modulation. Respiratory dyskinesia, a side effect of levodopa therapy, may produce both restrictive and dyskinetic ventilation. Therapy with ergot derivatives may result in pleuropulmonary fibrosis. Lastly, pulmonary infection as a consequence of disordered respiratory mechanics continues to contribute significantly to morbidity and mortality in PD.

Antiparkinson Agents↗
PubMed1996

Effectiveness of clozapine and a social learning program for severely disabled psychiatric inpatients.

OBJECTIVE: This study examined the combined effectiveness of clozapine and a comprehensive inpatient psychosocial rehabilitation program on the clinical functioning and aggressive behaviors of patients with chronic schizophrenia. METHODS: Two groups of 11 subjects each were selected from among patients being treated in the social learning program at Fulton (Mo.) State Hospital. Group 1 subjects were placed on clozapine at various times after the introduction of the program, while group 2 subjects remained on traditional antipsychotics throughout the study period. Group 1 and group 2 subjects were matched on clinical functioning as measured by the Time-Sample Behavioral Checklist (TSBC). For each subject, scores on six TSBC subscales were examined at five time points. Data were analyzed using repeated-measures multiple analysis of variance and univariate analyses of variance. Data on frequency of aggressive behaviors were aggregated into three six-month time periods and were analyzed using Wilcoxon signed-rank tests. RESULTS: Both groups demonstrated significant improvement on several measures. However, the addition of clozapine resulted in accelerated improvement for group 1 subjects, especially in aggressive behaviors. CONCLUSIONS: Comprehensive psychosocial treatment programming resulted in significant improvements in clinical functioning for many inpatients. Clozapine may enhance responsiveness to such programming for some patients.

Activities of Daily Living↗
PubMed1996

Treatment options for early Parkinson's disease.

Proper treatment of tremor in any clinical setting depends on correct diagnosis. Essential, or familial, tremor is symptomatic with movement and involves the limbs, head and voice. Parkinson's disease tremor occurs at rest, involves the jaw and limbs and is associated with bradykinesia, rigidity and falling. Parkinson's disease is treated with a number of medications, but levodopa, a dopamine precursor, is considered most effective. Other therapies in the early stages of Parkinson's disease may include neuroprotective agents, dopamine agonists, dopamine reuptake inhibitors, anticholinergics and/or amantadine. Polypharmacy is often necessary to minimize or avoid drug side effects.

Algorithms↗
PubMed1995

An open-labelled assessment of adverse effects associated with interferon 1-beta in the treatment of multiple sclerosis.

Interferon 1-beta (IFNB) (Betaseron) has been reported to reduce the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (MS). Adverse effects from this every other day injection are frequent, and most often include injection site reaction or flu-like symptoms. This open-labelled prospective study of MS patients receiving IFNB found that while injection site reactions and flu-like symptoms were seen in 90.0% and 76.7% of patients respectively, only two of 30 patients discontinued therapy for these problems.

Adjuvants, Immunologic↗
PubMed1993

Current approaches in the treatment of Parkinson's disease.

Treatment options for patients with Parkinson's disease have rapidly expanded in the last five years. They now include pharmacologic therapies designed not only to improve parkinsonian symptoms, but also to prevent disease progression. In addition, neurosurgical options and other novel treatment strategies are being developed and may become clinically useful in the next decade. This chapter addresses current and evolving Parkinson's disease medications, future surgical interventions, and specific strategies for maximizing patient motor abilities.

Antiparkinson Agents↗