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Biomedical subjects

A Brashear

Publications and source records attributed to A Brashear.

At least 19 recordsLinked to original sources
PubMed2001

Cervical dystonia severity scale reliability study.

Cervical dystonia (CD) is characterized by sustained contractions of the neck musculature, resulting in abnormal head postures. The Cervical Dystonia Severity Scale (CDSS) was developed to provide a reliable measure of treatment response in patients with CD. The CDSS uses a protractor and wall chart to rate the severity of the head's deviation from neutral in each of three planes of motion (rotation, laterocollis, anterocollis/retrocollis), which is then scored in 5 degree intervals (1 degree to 5 degrees deviation = 1; 86 degree to 90 degrees deviation = 18). To test the reliability of the CDSS, four centers, each with two independent examiners, evaluated 42 patients with CD. At each site, each of the two examiners used the CDSS to evaluate the head position of each patient twice, on the same day, for a total of four evaluations. The kappa value for intra-examiner agreement was 0.94 (95% confidence limit of 0.900-0.972), indicating excellent intra-examiner reliability. The kappa value for interexaminer reliability was 0.79 for the first evaluation and 0.86 for the second evaluation (95% confidence limits of 0.668-0.920 and 0.790-0.920) indicating excellent interexaminer reliability. Thus, the CDSS was highly reliable in both intra-examiner and interexaminer scoring comparisons.

Adult↗
PubMed2001

The botulinum toxins in the treatment of cervical dystonia.

The use of botulinum toxin to treat cervical dystonia (CD) has dramatically improved the quality of life of patients with this disabling, often painful disease. Two forms of toxins, botulinum toxin type A (BTX-A) and botulinum toxin type B (BTX-B), have each been studied in large multicenter trials in subjects with CD. A study of BTX-A demonstrated improvement of 5.15 to 10.65 degrees in head position using the Cervical Dystonia Severity Scale (CDSS) in those treated with BTX-A (trade name BOTOX) compared with placebo. A study in patients who continued to respond to BTX-A and a similarly designed study in patients who were resistant to BTX-A demonstrated statistical improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in those treated with BTX-B (evaluated as NeuroBloc) compared with placebo. The potential availability of both forms of toxin will allow physicians to offer further treatment options to patients with CD.

Botulinum Toxins↗
PubMed2001

Botulinum toxin type B: a new injectable treatment for cervical dystonia.

Cervical dystonia (CD) causes involuntary muscle spasms and is often associated with pain. Recently, botulinum toxin type B (BTX-B) (Myobloc, Elan South San Francisco, CA, USA) was approved for general use in the treatment of CD in the USA. In two large pivotal trials, BTX-B was found to be safe and effective in decreasing the movements, pain and disability associated with CD. Benefits were noted both in patients who no longer respond and in those who continue to respond to botulinum toxin type A (BTX-A). BTX-B offers an additional therapeutic option for patients with CD.

Animals↗
PubMed2001

Botulinum toxin type a neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial.

BACKGROUND: Focal spasticity of the gastrocnemius-soleus muscles causes equinus gait in children with cerebral palsy (CP). Botulinum toxin type A (BTX-A), a neuromuscular blocking agent, reduces muscle tone/overactivity in dystonia, stroke, and CP. OBJECTIVE: A prospective, open-label, multicenter clinical trial evaluated the long-term safety and efficacy of repeated intramuscular injections of BTX-A on equinus gait in CP children. METHODS: Nine centers enrolled 207 children. BTX-A injections (4 U/Kg) were given approximately every 3 months (maximum dose 200 U per treatment). Outcome measures included a Physician Rating Scale of gait, ankle range of motion measurements, and the incidence and profile of adverse events. RESULTS: One hundred fifty-five (75%) of 207 children completed at least 1 year with a total of 302 patient years of BTX-A treatment. The mean duration of BTX-A exposure was 1.46 years per patient. Dynamic gait pattern on the Physician Rating Scale improved in 46% of patients (86/185) at first follow-up. The response was maintained in 41% to 58% of patients for 2 years. Both gait pattern and ankle position improved at every visit. The most common treatment-related adverse events included increased stumbling, leg cramps, leg weakness, and calf atrophy in 1% to 11% of patients. No treatment-related serious adverse events were reported. Only 6% (7/117) of patients with pre- and postantibody samples had both detectable antibodies and a subsequent treatment failure. CONCLUSION: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait.

Adolescent↗
PubMed2000

Patients' perception of stopping or continuing treatment of cervical dystonia with botulinum toxin type A.

Despite widespread commercial acceptance of botulinum toxin (BTX) for idiopathic cervical dystonia (ICD), no follow up has been performed to determine when and why some patients stop therapy. It has been suggested that some patients who stop BTX treatment may do so because of permanent improvement. We surveyed 155 patients with ICD who were treated over 6 years with BTX to determine when and why patients stopped treatment with BTX, and what adverse events and changes in dose and/or frequency of treatments occurred in those who continued treatment. Of the 133 (86.6%) individuals returning the surveys, 104 continued on BTX treatment and 29 had stopped therapy. Of the 29 subjects no longer receiving BTX, 11 individuals had only received one or two injections. Prior surgical treatment for ICD did not influence their decision to stop therapy. Of those 104 of 133 continuing on BTX treatments, two thirds of the subjects reported the injections always help, whereas one quarter estimated one set of injections did not help. One third of those continuing treatment reported the first injection was most helpful, whereas another one third felt all injections were similarly effective. After an initial adjustment, BTX dosages and frequency of treatment remained stable in this group.

Adult↗
PubMed2000

Duration of effect of botulinum toxin type A in adult patients with cervical dystonia: a retrospective chart review.

BACKGROUND: Clinical trials have established the efficacy and safety of botulinum toxin type A (BTX-A) in patients with cervical dystonia. To maintain the clinical benefits of BTX-A, injections need to be repeated whenever patients' symptoms begin to recur. OBJECTIVE: The purpose of this study was to determine, in clinical practice settings, the mean duration of effect of BTX-A in the treatment of adult patients with cervical dystonia. METHODS: A retrospective chart review was undertaken at an academic center and a private neurology practice. At each site, > or =50 patients being treated for cervical dystonia were identified and randomized for chart review. Patients had to have received the first assessable injection of BTX-A between January 1, 1998, and March 31, 1998, to coincide with the clinical availability of the most current formulation of the neurotoxin. A chart was eligible for review if the patient was aged > or =18 years, had a documented diagnosis of idiopathic cervical dystonia, was being treated with BTX-A, and had been under the continuous care of investigators from January 1, 1998, to August 31, 1999. Of the 102 patients initially identified, the first 30 from each site who met the study inclusion criteria were assessed for (1) age and sex; (2) severity of dystonia; (3) years of BTX-A use; (4) dates of first, second, third, and fourth BTX-A injections; (5) drug dose; (6) use of electromyography; (7) use of other prescribed therapies; (8) laboratory tests; and (9) adverse events. The mean interval between each visit and mean per-patient duration of effect were calculated and stratified by patient characteristics. RESULTS: The mean age of the patients was 56.4 years. Two thirds of the patients were women. Forty-one of the 60 patients (68.3%) had either moderate or severe disease, and 48 (80.0%) had experienced cervical dystonia for >5 years. The mean per-patient duration of effect across the 4 visits was 15.5 weeks (range, 12.2-24.3 weeks). The duration of effect did not differ significantly between study sites despite the differences in disease severity, drug dose, and use of adjunctive therapy. CONCLUSION: BTX-A the controls symptoms of cervical dystonia for 12 to 24 weeks, with a mean duration of effect per patient of 15.5 weeks.

Botulinum Toxins, Type A↗
PubMed2000

The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: summary of three controlled clinical trials.

Cervical dystonia (CD) is characterized by abnormal, involuntary contractions of the cervical and/or shoulder muscles. Direct injection of Botulinum toxin type A (BTX-A) into the affected muscles has been used successfully to treat this condition. However, clinical resistance to BTX-A therapy develops in a limited number of patients. Moreover, an unknown proportion of treated patients have a suboptimal response to their present therapy. BTX-B is antigenically distinct from BTX-A and possesses a different mechanism of action. Three randomized, double-blind, placebo-controlled clinical trials evaluated the safety and efficacy of BTX-B (Elan's BTX-B evaluated as NeuroBloc) as a treatment for patients with CD. Patients received a single dose of BTX-B ranging from 2,500 to 10,000 U. The primary efficacy evaluation for each of these studies used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. Additional efficacy measures included the TWSTRS severity, disability, and pain subscale scores, as well as the Patient Analog Pain Assessment and Patient's and Physician's Global Assessments of Change. In all three studies, groups receiving BTX-B displayed statistically significant improvements in TWSTRS total score and other efficacy end points compared with those who received placebo treatment. The clinical benefits after BTX-B treatment lasted 12 to 16 weeks and were observed in both BTX-A-responsive and BTX-A-resistant patients. In general, treatment with BTX-B was well tolerated and most of the reported adverse events were of short duration, mild to moderate in severity, and anticipated. The results from the three controlled clinical trials demonstrate the safety and efficacy of BTX-B in the treatment of patients with CD, including those who are resistant to BTX-A treatment.

Botulinum Toxins↗
PubMed1999

Metrifonate treatment of AD: influence of APOE genotype.

OBJECTIVE: To investigate whether an interaction exists between APOE genotype and the response of AD patients to metrifonate treatment and whether APOE genotype independently affects the rate of AD progression. BACKGROUND: Metrifonate is a new acetylcholinesterase inhibitor for the treatment of AD symptoms. METHODS: Data were pooled from four prospective, randomized, double-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifonate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. RESULTS: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog], p = 0.0001). The interaction of APOE genotype and the metrifonate effect on cognitive performance were not significant (p = 0.25). Metrifonate also clearly improved the global function of the AD patients when compared with placebo (Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70). No significant three-way interactions were observed among APOE genotype, gender, and response to metrifonate treatment (ADAS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC-Plus, p = 0.64). CONCLUSIONS: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects. They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD.

Aged↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

Adult↗
PubMed1999

Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13.

Rapid-onset dystonia-parkinsonism (RPD) is an autosomal dominant movement disorder characterized by sudden onset of persistent dystonia and parkinsonism, generally during adolescence or early adulthood. Symptoms evolve over hours or days, and generally stabilize within a few weeks, with slow or no progression. Other features include little or no response to L-dopa, and low levels of homovanillic acid in the central nervous system. Neuroimaging studies indicate no degeneration of dopaminergic nerve terminals in RDP, suggesting that this disorder results from a functional deficit, as in dystonia, rather than neuronal loss, as in Parkinson's disease. We studied 81 members of two midwestern US families with RDP, 16 of whom exhibited classic features of RDP. We found significant evidence for linkage in these two families to markers on chromosome 19q13, with the highest multipoint LOD score at D19S198 (z = 5.77 at theta = 0.0). The flanking markers D19S587 and D19S900 define a candidate region of approximately 8 cM. Although RDP itself is a rare condition, it is important because it has clinical and biochemical similarities to both Parkinson's disease and dystonia. Identification of the genetic defect in RDP holds promise for understanding the underlying disease processes of both of these more common diseases.

Adolescent↗
PubMed1999

PET imaging of the pre-synaptic dopamine uptake sites in rapid-onset dystonia-parkinsonism (RDP).

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement disorder characterized by abrupt onset over hours to days of bradykinesia, postural instability, dysphagia, dysarthria, and severe dystonic spasms with decreased levels of the dopamine metabolite, homovanillic acid (HVA), in cerebrospinal fluid (CSF). METHODS: We imaged the dopamine re-uptake system with [O-methyl-11C]beta-CFT ([11C]beta-CFT) in three severely affected individuals with RDP and four patients with idiopathic Parkinson's disease (IPD). Results were compared with those of age-matched normal volunteers. RESULTS: Positron emission tomography images from those patients with IPD demonstrated a dramatic reduction in the volume of distribution of [11C]beta-CFT whereas patients with RDP showed slightly elevated values. CONCLUSIONS: The data suggest that patients with RDP do not have a decrease in the number of dopamine re-uptake sites. Our findings suggest that, unlike the situation in IPD, low CSF HVA concentrations seen in RDP patients are not the result of degeneration of striatal dopamine terminals or loss of dopamine re-uptake sites.

Adult↗
PubMed1999

Rapid onset dystonia-parkinsonism in a 14-year-old girl.

A painful dystonia of rapid onset and associated parkinsonian features is described in a girl aged 14 years. The condition is refractory to treatment and has led to severe neurological disability. Her father had presented with a similar picture.

Adolescent↗
PubMed1998

Cerebrospinal fluid homovanillic acid levels in rapid-onset dystonia-parkinsonism.

Rapid-onset dystonia-parkinsonism (RDP) is characterized by sudden onset over hours to days of dystonia, dysphagia, dysarthria, and parkinsonism. RDP has been reported by our group in two apparently unrelated families. We now report analysis of cerebrospinal fluid metabolites of dopamine, norepinephrine, and serotonin for mild and severely affected individuals, known asymptomatic gene carriers, and at-risk individuals from both families with RDP. Levels of the dopamine metabolite homovanillic acid (HVA) were decreased in severely affected patients and in some asymptomatic gene carriers. HVA levels increased with treatment in some affected individuals, but this increase did not predict clinical response to carbidopa/levodopa. We suggest that a low HVA level is a biological marker with modest association to the diagnosis of RDP.

Adult↗
PubMed1998

Comparison of treatment of tardive dystonia and idiopathic cervical dystonia with botulinum toxin type A.

To compare clinical parameters of patients treated with botulinum toxin type A (BTX) for treatment of idiopathic cervical dystonia (ICD) and for tardive cervical dystonia (TCD), we studied 156 patients (149 with ICD and 7 with TCD) who were treated with serial injections of BTX over 5 years. We hypothesized that patients with TCD and ICD would demonstrate similar improvement in severity scores after treatment with BTX. The diagnosis, dates, dosages, and frequency of BTX injected and severity assessments were recorded into a computerized database. Nonparametric Wilcoxon rank sum and signed-rank tests were used to assess statistical significance. The change in severity scores between the first treatment and last treatment in both groups was not statistically significant (p = 0.4859), indicating similar improvement. The difference in BTX doses was significant (p = 0.0045). ICD patients (n = 149) received an average of 219.8 +/- 63.5 units and those with TCD (n = 7) were treated with an average dose of 287.4 +/- 60.3 units. The average number of days between treatments for individuals with ICD was 142.9 +/- 85.8, similar to that for persons with TCD (144.7 +/- 64.5) (p = 0.6075). Our analysis provides preliminary evidence that the improvement from the administration of BTX for patients with ICD and TCD is similar.

Adult↗
PubMed1997

Focal dystonia after chemotherapy: a case series.

Dystonia is a rare neurologic disorder of the basal ganglia presenting with involuntary twisting or turning spasm of muscles. Movements localized to the face, eyes, or neck generally present during late adulthood. Cranial dystonia is usually idiopathic but may be caused by trauma or medications. Of 148 patients with focal dystonia referred to Indiana University over four years, four women had the onset of face and neck symptoms eight days to 34 months after completing treatment with chemotherapy alone or combined with radiation therapy. Two patients were treated with 5-FU, one received doxorubicin and one was treated with both. Both drugs have been associated with transient parkinsonism, but no chemotherapeutic medications have been reported to cause dystonia. Three patients remain free of demonstrable malignancy. A possible association of chemotherapy and focal dystonia has not been previously described.

Adenocarcinoma↗
PubMed1997

Rapid-onset dystonia-parkinsonism in a second family.

Rapid-onset dystonia-parkinsonism (RDP), first described in a large Midwestern family, is now reported in a second, apparently unrelated, family in which four individuals have this same syndrome. All four developed sudden onset of dysarthria, dysphagia, severe dystonic spasms, bradykinesia, and postural instability over less than 1 hour to a few days. Three of the four had stable limb dystonia for several years preceding the onset of combined dystonia-parkinsonism. Treatment with levodopa/carbidopa provided little benefit. We propose diagnostic criteria for RDP and further define the spectrum of this unusual disease.

Adolescent↗
PubMed1997

Costs of treating dystonias and hemifacial spasm with botulinum toxin A.

Botulinum toxin (BTX) has become a safe and effective therapeutic tool in the treatment of a variety of neurological disorders, especially dystonias. One major disadvantage, however, is the high cost of a single injection of BTX. In this study of 835 patients, we calculated the cost of treatment with BTX serotype A (BTX-A) for different dystonias and hemifacial spasm. The annual expenditure per patient for BTX-A injections in this cohort totalled (mean +/- standard deviation) 1030 Deutschmarks (DM) [1996 values] +/- DM610 [$US570 +/- $US340; 230 +/- 130 pounds sterling (Pound)] for blepharospasm (n = 158), DM1450 +/- DM1520 ($US800 +/- $US830; 310 Pounds +/- 280 Pounds) for craniocervical dystonia (n = 148), and DM1480 +/- DM780 ($US810 +/- $US430; 330 Pounds +/- 180 Pounds) for oromandibular dystonia (n = 16), while the treatment of cervical dystonia consumed DM4590 +/- DM2060 ($US2520 +/- $US1130; 960 Pounds +/- 420 Pounds) [n = 362] per patient. In order to alleviate symptoms in patients with hemifacial spasm (n = 151), DM510 +/- DM270 ($US280 +/- $US150; 110 Pounds +/- 60 Pounds) had to be spent annually. The expenses for surgical therapy for cervical dystonia were DM10,120 +/- DM1900 (n = 54). No major differences concerning expenditure could be found in this study between the 2 available preparations of BTX. However, there appeared to be a lower rate of adverse effects with the Botox formulation, compared with the Dysport formulation, of BTX-A (this difference was statistically significant, i.e. p < 0.001). Although the cost of an individual injection is high, other cost factors also substantially contribute to the societal costs of adult-onset dystonias. Some of these costs may be attenuated with the use of BTX. The subjective and objective relief of these socially devastating and sometimes painful conditions rewards the expenditure associated with the use of BTX-A.

Adult↗