The impact of fibrodysplasia ossificans progressiva (FOP) on patients and their family members: results from an international burden of illness survey.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, genetic disorder of heterotopic ossification within soft, connective tissues resulting in limited joint function and severe disability. We present results from an international burden of illness survey (NCT04665323) assessing physical, quality of life (QoL), and economic impacts of FOP on patients and family members. METHODS: Patient associations in 15 countries invited their members to participate; individuals with FOP and their family members were eligible. The survey was available online, in 11 languages, from 18 January-30 April 2021. Participants responded to assessments measuring joint function, QoL, healthcare service and living adaptation utilization, out-of-pocket costs, employment, and travel. RESULTS: The survey received 463 responses (patients, n = 219; family members, n = 244). For patients, decreased joint function was associated with reduced QoL and greater reliance on living adaptations. Nearly half of primary caregivers experienced a mild to moderate impact on their health/psychological wellbeing. Most primary caregivers and patients (≥18 years) reported that FOP impacted their career decisions. CONCLUSIONS: Data from this survey will improve understanding of the impact of FOP on patients and family members, which is important for identifying unmet needs, optimizing care, and improving support for the FOP community.

Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study.

AIM: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). METHOD: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. RESULTS: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively). INTERPRETATION: Treatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles. WHAT THIS PAPER ADDS: AbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.

The Effect of Repeated abobotulinumtoxinA (Dysport®) Injections on Walking Velocity in Persons with Spastic Hemiparesis Caused by Stroke or Traumatic Brain Injury.

BACKGROUND: Botulinum toxin (BoNT) injections were shown to improve muscle tone of limbs in patients with spasticity. However, limited data are available regarding the effects of repeated BoNT injections on walking ability. OBJECTIVE: To assess changes in walking velocity (WV), step length, and cadence under different test conditions after repeated treatment with abobotulinumtoxinA (aboBoNT-A; Dysport) in spastic lower limb muscles. DESIGN: Secondary analysis of an open-label, multiple-cycle extension (National Clinical Trials number NCT01251367) to a phase III, double-blind, randomized, placebo-controlled, single-treatment cycle study, in adults with chronic hemiparesis (NCT01249404). SETTING: Fifty-two centers across Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia, and the United States. PATIENTS: 352 Ambulatory adults (18-80 years) with spastic hemiparesis and gait dysfunction caused by stroke or traumatic brain injury, with a comfortable barefoot WV of 0.1 to 0.8 m/s. INTERVENTIONS: Up to four aboBoNT-A treatment cycles, administered to spastic lower limb muscles. MAIN OUTCOME MEASUREMENTS: Changes from baseline in comfortable and maximal barefoot and with shoes WV (m/s), step length (m/step), and cadence (steps/minutes). RESULTS: At Week 12 after four injections, WV improved by 0.08 to 0.10 m/s, step length by 0.03 to 0.04 m/step, and cadence by 3.9 to 6.2 steps/minutes depending on test condition (all P < .0001 to .0003 vs baseline). More patients (7% to 17%) became unlimited community ambulators (WV ≥0.8 m/s) across test conditions compared with baseline, with 39% of 151 patients classified as unlimited community ambulators in at least one test condition and 17% in all four test conditions. CONCLUSIONS: Clinically meaningful and statistically significant improvements in WV, step length, and cadence under all four test conditions were observed in patients with spastic hemiparesis after each aboBoNT-A treatment cycle.

Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA. DESIGN: Secondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study. SETTING: Fifty-two centers (11 countries). PATIENTS: Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb. MAIN OUTCOME MEASUREMENTS: Muscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented. RESULTS: Of 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA. CONCLUSIONS: Patients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

Efficacy of Repeat AbobotulinumtoxinA (Dysport®) Injections in Improving Gait in Children with Spastic Cerebral Palsy.

Purpose: This secondary analysis of a randomized, double-blind study plus open-label extension (NCT01249417/NCT01251380) evaluated the efficacy of abobotulinumtoxinA versus placebo in improving gait pattern in children with dynamic equinus due to cerebral palsy (CP) as assessed by the observational gait scale (OGS). Methods: Ambulatory children with CP (N = 241, aged 2-17) and dynamic equinus were randomized to treatment with abobotulinumtoxinA (10 or 15U/kg/leg) or placebo injected into the gastrocsoleus. All children received abobotulinumtoxinA in the open-label phase. Results: In the double-blind phase, abobotulinumtoxinA significantly improved OGS total scores versus placebo at Week 4 (treatment effect vs. placebo: 10U/kg/leg: 1.5 [0.7, 2.3], p = .0003; 15U/kg/leg: 1.1 [0.3, 1.9], p = .01). In the open-label phase, treatment with abobotulinumtoxinA continued to improve the OGS score at the same magnitude as seen in the double-blind study. Conclusion: Repeat treatment with abobotulinumtoxinA improved gait in children with dynamic equinus.

Effects of repeated abobotulinumtoxinA injections in upper limb spasticity.

INTRODUCTION: The efficacy of single injections of abobotulinumtoxinA (Dysport) is established in adults with upper limb spasticity. In this study we assessed the effects of repeated injections of abobotulinumtoxinA over 1 year. METHODS: Patients (n = 258, safety population) received 500 U, 1,000 U, or 1,500 U (1,500-U dose included 500-U shoulder injections) for up to 4 or 5 treatment cycles. Assessments included treatment-emergent adverse events (TEAEs), muscle tone, passive and active range of motion (XV1, XA ), angle of catch (XV3 ), Disability Assessment Scale (DAS) score, Modified Frenchay Scale (MFS) score, and Physician Global Assessment (PGA) score. RESULTS: The incidence of TEAEs decreased across cycles. Muscle tone reduction and XV1 remained stable across cycles, whereas XV3 and XA continued to improve at the finger, wrist, and elbow flexors. DAS and PGA improved across cycles. MFS improved best with 1,500 U. DISCUSSION: A favorable safety profile and continuous improvements in active movements and perceived and active function were associated with repeated abobotulinumtoxinA injections in upper limb muscles. Muscle Nerve 57: 245-254, 2018.

Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension.

OBJECTIVE: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius-soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint. RESULTS: After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: -0.5 (-0.7 to -0.4) (placebo, n = 128), -0.6 (-0.8 to -0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and -0.8 (-0.9 to -0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached -1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile. CONCLUSIONS: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation. CLINICALTRIALGOV IDENTIFIERS: NCT01249404, NCT01251367. CLASSIFICATION OF EVIDENCE: The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone.

Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy.

This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ≥1 open label injection into the gastrocnemius-soleus; 17-24% of patients also had injections into the hamstrings. The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain (n = 10). There was no evidence of a cumulative effect on adverse events. Sustained significant clinical improvements in muscle tone (Modified Ashworth Scale), spasticity (Tardieu Scale), overall clinical benefit (Physicians Global Assessment), and goal attainment (Goal Attainment Scale) were also observed across treatment cycles.

Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A). DESIGN: A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299). SETTING: A total of 34 neurology or rehabilitation clinics in 9 countries. PARTICIPANTS: Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male. INTERVENTION: Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb. MAIN OUTCOME MEASUREMENTS: Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events. RESULTS: At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events. CONCLUSIONS: The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is a treatment option in these patients, and no difference in initial dosing appears to be required compared to that in individuals not treated previously. LEVEL OF EVIDENCE: III.

AbobotulinumtoxinA (Dysport®) Improves Function According to Goal Attainment in Children With Dynamic Equinus Due to Cerebral Palsy.

This secondary analysis of a large (n = 241), randomized, double-blind study evaluated the efficacy of 2 doses of abobotulinumtoxinA + standard of care (SOC) versus placebo + SOC in enabling children with dynamic equinus due to cerebral palsy to achieve their functional goals using Goal Attainment Scaling. Most parents/caregivers selected goals targeting aspects of gait improvement as most relevant. Mean (95% confidence interval) Goal Attainment Scaling T scores at week 4 were higher for both abobotulinumtoxinA groups versus placebo (treatment difference vs placebo: 10 U/kg/leg: 5.32 [2.31, 8.32], P = .0006, and 15 U/kg/leg 4.65 [1.59, 7.71], P = .0031). Superiority of both abobotulinumtoxinA doses versus placebo was maintained at week 12. Best goal attainment T scores were higher in the abobotulinumtoxinA groups versus placebo for the common goals of improved walking pattern, decreased falling, decreased tripping, and improved endurance. These findings demonstrate that single injections of abobotulinumtoxinA (10 and 15 U/kg/leg) significantly improved the ability of pediatric cerebral palsy patients to achieve their functional goals.

Group and individual cognitive therapies in Alzheimer's disease: the ETNA3 randomized trial.

BACKGROUND: Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care. METHODS: This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization. RESULTS: No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced. CONCLUSIONS: These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.

High sensitivity C reactive protein, fibrinogen levels and the onset of major depressive disorder in post-acute coronary syndrome.

BACKGROUND: Major depression disorder (MDD) is a common condition in patients suffering from acute coronary syndrome (ACS), and depression is a risk factor for mortality following an ACS. Growing evidence suggests that there is an intricate interplay between atherosclerosis, inflammation and depression. The aim of this study was to investigate the role of atherosclerosis-induced inflammation in the mediation of MDD. METHODS: 87 patients without depression were recruited at the time of an ACS, evaluated at 3 and 7 days and followed at 1, 3 and 9 months for the occurrence of a MDD as assessed by structured interviews (MINI). At each time point, they were monitored for inflammatory markers (high sensitivity C Reactive Protein {hsCRP} and fibrinogen), cardiovascular risk factors and atherosclerosis burden. Association between possible predictive characteristics and depression was assessed using a multivariable logistic regression model. RESULTS: The overall incidence of MDD, in this population, was 28.7% [95% CI: 19.5 - 39.4] during the 9-month follow up period. Elevated hsCRP was not associated with depression onset after an ACS (adjusted OR: 1.07 [0.77 - 1.48]; p = 0.70), and similarly no association was found with fibrinogen. Furthermore, we found no association between hsCRP, fibrinogen or atherosclerosis burden at any time-point, and the occurrence of a MDD (or HDRS-17 and MADRS). The only factor associated with depression occurrence after an ACS was a previous personal history of depression (adjusted OR: 11.02 [2.74 to 44.34]; p = 0.0007). CONCLUSIONS: The present study shows that after an ACS, patients treated with optimal medications could have a MDD independent of elevated hsCRP or fibrinogen levels. Personal history of depression may be a good marker to select patients who should be screened for depression after an ACS.

Comparative cost-effectiveness analysis of sacral anterior root stimulation for rehabilitation of bladder dysfunction in spinal cord injured patients.

BACKGROUND: Urinary disorders account for 10% of deaths in patients with complete spinal cord injury. Sacral anterior root stimulation (SARS) may be a valuable therapeutic option to restore complete and voluntary micturition (CVM), but questions on its cost-effectiveness remain. OBJECTIVE: To evaluate the cost-effectiveness of SARS to restore CVM in patients with complete spinal cord injury. METHODS: We conducted a nonrandomized, multicenter, parallel-group cohort study comparing SARS vs. current medical treatments with catheterization or reflex micturition. CVM was assessed at 12 months (end of follow-up) by urodynamic examination. Medical and nonmedical costs were measured in the perspective of the French national health insurance. Linear regression models were used to estimate the incremental net benefit ((Equation is included in full-text article.); λ = willingness-to-pay) adjusted for potential confounders, and P (INB >0) (i.e., probability of SARS being cost-effective vs medical treatment) for different values of λ. RESULTS: Twenty-five patients were included in each group in 2005 to 2009. At inclusion, mean age was 41 years; 45 (90%) patients were male, and 29 (59%) patients were paraplegic. At 12 months, 15 (60%) patients with SARS had a CVM vs. 3 (12%) patients with medical treatment (P < .001). The total mean cost was 42,803 €; and 8762 €, respectively (P < .001). After adjustment for CVM and voiding methods at inclusion, P (INB >0) was 74% at λ = 100,000 €. This probability was 94% in a sensitivity analysis excluding 6 patients presenting a CVM at inclusion. CONCLUSION: The effectiveness and cost of SARS are much higher than for medical treatment. Our results inform decision makers of the opportunity to reimburse SARS in this vulnerable population.

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial.

PURPOSE: Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI. METHODS: This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period. RESULTS: Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups. CONCLUSIONS: In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.

BN82451 attenuates L-dopa-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.

The development of L-dopa-induced dyskinesia (LID) remains a major problem in the long-term treatment of Parkinson's disease (PD). This study aimed to assess the effect of the multitargeting molecule BN82451 on LID and to measure striatal mRNA expression of several genes in a rat model of PD. Rats were administered two unilateral injections of 6-OHDA in the striatum. After four weeks, the animals started a chronic daily treatment with increasing doses of L-dopa over a further four-week period. Over the course of L-dopa treatment, the rats developed abnormal involuntary movements (AIMs) classified as locomotive, axial, orolingual and forelimb dyskinesia. In animals rendered dyskinetic by L-dopa, administration of BN82451 at doses ranging from 1 to 10 mg/kg p.o. attenuated the severity of fully-established AIMs in a dose-related manner. This anti-dyskinetic effect could be achieved with lower doses of BN82451 administered sub chronically vs. acute single treatment. The improvement of AIMs is not due to a reduction in the general motor activity of dyskinetic rats. BN82451 treatment significantly reversed the overexpression of c-Fos, FosB and Arc mRNA associated with the dyskinesiogenic action of L-dopa. A significant correlation between the degree of overexpression of c-Fos, FosB and Arc mRNA and the dyskinesiogenic action of L-dopa was observed. The data demonstrate that BN82451 effectively attenuates LID and the associated molecular alterations in an animal model of PD and may represent a treatment option for managing dyskinesia.