Treating spastic equinus foot from cerebral palsy with botulinum toxin type A: what factors influence the results?: an analysis of 189 consecutive cases.

OBJECTIVE: The aim of this study was to determine the variables that improve spastic equinus foot caused by cerebral palsy when treated with botulinum toxin type A. DESIGN: We reviewed all patients treated for spastic equinus foot using botulinum toxin type A (Botox) in the triceps suralis during a 3 1/2-yr period and analyzed the results after the first injection. There were 117 patients (72 diplegic and 45 hemiplegic patients) and a total of 189 triceps suralis treated. Variables analyzed included age, total dose per session, total dose per kilogram for each session, total dose per triceps, triceps dose per kilogram, type of cerebral palsy, cognitive level, botulinum toxin dilution, and physiotherapy. Assessments of efficacy were done using a Global Assessment Scale rated independently by parents, therapists, and a neurologist; the Modified Ashworth Scale; and the Modified Physician Rating Koman scale. RESULTS: Improvement was observed in all scales (P < 0.001). The change of foot position during walking was the best parameter for measuring improvement. There was correlation between the grade of improvement and the dose per kilogram for each triceps suralis (P < 0.001). Patient age was inversely correlated with improvement (P = 0.043). Diplegic and hemiplegic patients improved similarly, but the hemiplegic patients required higher doses for each muscle (P < 0.001). The most effective dose for diplegic patients was 3-4 IU/kg for each triceps, compared with 4-6 IU/kg for hemiplegic patients. Different dilutions of Botox (100, 50, and 40 U/ml) resulted in similar outcomes. No better results were achieved when 2-3 sessions/wk of physiotherapy was added to a daily program of exercises at home to enhance foot dorsiflexion. CONCLUSIONS: The dose per kilogram of Botox injected into triceps suralis and the patient age influence the results. The most effective dose is different between diplegic and hemiplegic patients. The concentration of botulinum toxin type A does not play a significant role in the outcome.

Evolution of dose and response to botulinum toxin A in cervical dystonia: a multicenter study.

Botulinum neurotoxin (BoNT) is an effective treatment for cervical dystonia (CD). Long-term changes of several variables, including the dose of BoNT, in these patients is largely unknown. We reviewed the clinical charts of 275 patients with CD treated with BoNT type A (BoNT-A) for at least 5 years since 1989 at ten tertiary centers. The mean dose of BoNT-A per session during the first 5 years of treatment was calculated and the appearance of resistance was noted. The dose of BoNT-A for the whole group showed a significant trend to increase over time (year 1: 180 ± 65 U; year 5: 203 ± 63 U; ANOVA: p < 0.0001). However, when we studied the evolution of the dose of BoNT-A for those patients (n = 49) first injected after 2000 (introduction of current BOTOX preparation in our country), there was no significant increase in dose (year 1: 181.8 ± 75 U; year 5: 181.7 ± 75 U; ANOVA p: ns). A total of 19 patients became secondary nonresponders; all but one of these patients began BoNT-A treatment before 2000. In summary, there is a statistically significant increase of mean dose of BoNT-A per session over time, and this could be explained by the appearance of secondary nonresponders. On the other hand, those patients initially treated after 2000 did not show any statistically significant increase in dose for 5 years. This could be explained by better experience and techniques, fewer immunogenic problems with the current BoNT-A, and also less variability of the dose per vial.

Motor complications in Parkinson's disease: ten year follow-up study.

Parkinson's disease (PD) can be symptomatically controlled with standard treatments; however, after a few years, this response typically declines and most patients develop motor complications. We carried out a prospective practice-based study to evaluate the evolution appearance and evolution of motor complications in 64 de novo PD patients over 5 years and in 38 PD patients over 10 years. We studied untreated patients from initial assessment at basal conditions and evaluated every 6 months thereafter with treatment (levodopa versus other drugs). The follow-up assessments were performed with the Unified Parkinson's Disease Rating Scale (UPDRS). At each assessment, patients were monitored regarding the development of dyskinesias, motor fluctuations, freezing, loss of postural reflexes, and cognitive impairment. We observed a significant improvement in UPDRS scores during the first year, then a progressive decline, more evident after the third year. Motor complications increased after the third year, and at the end of the survey (tenth year); drug-induced dyskinesias and motor fluctuations were experienced (71.1 and 94.7%, respectively). After the first decade, many complications arose from the non-levodopa-responsive features of the disease (cognitive impairment was present in 52.6% and gait freezing in 71.1%). Initial medication may influence medium-term complications but not long-term problems. Most long-term disabling problems of PD were related to non-levodopa-responsive features.

Memory and exploratory impairment in mice that lack the Park-2 gene and that over-express the human FTDP-17 mutant Tau.

While mutations in the Park-2 gene are the most frequent cause of autosomal-recessive juvenile parkinsonism (AR-JP), they are also present in several forms of tauopathies. Conversely, in some forms of parkinsonism, mutations in the tau gene have also been observed. Deletion of the Park-2 gene and over-expression of mutant tau independently produce mild brain alterations in mice. However, the presence of both mutations simultaneously causes a tau neuropathology, involving reactive astrocytosis, neuron loss in the cortex and hippocampus, and lesions in nigrostriatal and motor neurons. Furthermore, mutant tau over-expression in mice produces important memory impairment. When "parkin" function was abolished in young tau transgenic mice, the memory alterations were exaggerated. Moreover, additional exploratory and motor deficits were observed in older mice, causing the memory alterations to be underestimated. Thus, while memory deficits are more severe in young mice they were somehow attenuated by exploratory impairments in ageing mutants. This double mutant animal will serve as a useful experimental tool to investigate the abnormal processing of hyperphosphorylated tau and its relationship to the development of the cognitive deficits associated with certain neurodegenerative diseases.

Capit timed tests quantify age-related motor decline in normal subjects.

Slowing of motor performance in human aging is a well demonstrated clinical observation. Age-related motor decline has been also confirmed in animal models including rodents and non human primates. We studied the motor performance of 60 normal subjects (age: 20-87). Motor study included the four timed tests (TT) recommended in CAPIT protocol: pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) or tapping, and walking test (WT). Finally we compared normal controls with a group of 30 patients with Parkinson's disease (PD) of similar age. Age inversely correlated with TT performance in normal subjects (for PS, r:0.33, p<0.01; FD, r:0.44, p<0.0005; MTP, r:0.51, p<0.0001; WT, r:0.59, p<0.0001, Pearson). Our results confirm that motor performance (measured with CAPIT TT) deteriorates linearly with age. Simple tasks, such as CAPIT TT can help to study and quantify age-related motor decline.