The effectiveness of peroneal nerve functional electrical simulation for the reduction of bradykinesia in Parkinson's disease: A feasibility study for a randomised control trial.

OBJECTIVES: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson's disease. DESIGN: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. SETTING: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. PARTICIPANTS: A total of 64 participants with idiopathic Parkinson's disease and slow gait <1.25 ms-1. INTERVENTIONS: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. MAIN MEASURES: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson's Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson's Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. RESULTS: There was a mean difference between groups of 0.14 ms-1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms-1 (CI -0.05, 0.25). There was a mean difference in UPDRS motor examination score of -3.65 (CI -4.35, 0.54) at week 18 which was lost at week 22 -0.91 (CI -2.19, 2.26). CONCLUSION: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

Correction of Footdrop Due to Multiple Sclerosis Using the STIMuSTEP Implanted Dropped Foot Stimulator.

Background: Footdrop is a significant problem in multiple sclerosis, reducing the safety and efficiency of walking. Functional electrical stimulation (FES) can produce dorsiflexion, correcting footdrop. The purpose of this retrospective analysis of clinical study data was to compare the effect of external and implanted FES devices for the correction of footdrop. Methods: External FES was used for a minimum of 6 months before implantation. Walking performance was assessed using 10-m walking speed, 3-minute walking distance, the Physiological Cost Index, and health- and device-related quality of life and device-use questionnaires. Assessments were made before implantation and a mean (SD) of 128 (24) days after surgery, with additional walking speed measurements at 3 years. Results: Twenty-three people with multiple sclerosis received the STIMuSTEP implant. Both devices enabled statistically significant increases in walking speed and walking distance, with a strong trend toward a reduced Physiological Cost Index, indicating that walking required less effort (P = .07). Both devices improved device-related quality of life. Walking speed gain with FES was maintained at 3 years. Three implants failed after falls, and there was one case of neuropraxia. The implant was used more days per week and was quicker to put on each day than the external FES device. Conclusions: The STIMuSTEP implanted dropped foot stimulator is an effective long-term intervention for the correction of footdrop.

Surface peroneal nerve stimulation in lower limb hemiparesis: effect on quantitative gait parameters.

OBJECTIVE: The objective of this study was to evaluate possible mechanisms for functional improvement and compare ambulation training with surface peroneal nerve stimulation vs. usual care via quantitative gait analysis. DESIGN: This study is a randomized controlled clinical trial. SETTING: The setting of this study is a teaching hospital of an academic medical center. PARTICIPANTS: One hundred ten chronic stroke survivors (>12 wks poststroke) with unilateral hemiparesis participated in this study. INTERVENTIONS: The subjects were randomized to a surface peroneal nerve stimulation device or usual care intervention. The subjects were treated for 12 wks and followed up for 6-mo posttreatment. MAIN OUTCOME MEASURES: Spatiotemporal, kinematic, and kinetic parameters of gait were the main outcome measures. RESULTS: Cadence (F3,153 = 5.81, P = 0.012), stride length (F3,179 = 20.01, P < 0.001), walking speed (F3,167 = 18.2, P < 0.001), anterior-posterior ground reaction force (F3,164 = 6.61, P = 0.004), peak hip power in preswing (F3,156 = 8.76, P < 0.001), and peak ankle power at push-off (F3,149 = 6.38, P = 0.005) all improved with respect to time. However, peak ankle ankle dorsiflexion in swing (F3,184 = 4.99, P = 0.031) worsened. In general, the greatest change for all parameters occurred during the treatment period. There were no significant treatment group × time interaction effects for any of the spatiotemporal, kinematic, or kinetic parameters. CONCLUSIONS: Gait training with peroneal nerve stimulation and usual care was associated with improvements in peak hip power in preswing and peak ankle power at push-off, which may have resulted in improved cadence, stride length, and walking speed; however, there were no differences between treatment groups. Both treatment groups also experienced a decrease in peak ankle ankle dorsiflexion in swing, although the clinical implications of this finding are unclear.

Randomized controlled trial of surface peroneal nerve stimulation for motor relearning in lower limb hemiparesis.

OBJECTIVE: To compare the motor relearning effect of a surface peroneal nerve stimulator (PNS) versus usual care on lower limb motor impairment, activity limitation, and quality of life among chronic stroke survivors. DESIGN: Single-blinded randomized controlled trial. SETTING: Teaching hospital of academic medical center. PARTICIPANTS: Chronic stroke survivors (N=110; >12wk poststroke) with unilateral hemiparesis and dorsiflexion strength of ≤4/5 on the Medical Research Council scale. INTERVENTIONS: Subjects were stratified by motor impairment level and then randomly assigned to ambulation training with either a surface PNS device or usual care (ankle-foot orthosis or no device) intervention. Subjects were treated for 12 weeks and followed up for 6 months posttreatment. MAIN OUTCOME MEASURES: Lower limb portion of the Fugl-Meyer (FM) Assessment (motor impairment), the modified Emory Functional Ambulation Profile (mEFAP) performed without a device (functional ambulation), and the Stroke Specific Quality of Life (SSQOL) scale. RESULTS: There was no significant treatment group main effect or treatment group by time interaction effect on FM, mEFAP, or SSQOL raw scores (P>.05). The time effect was significant for the 3 raw scores (P<.05). However, when comparing average change scores from baseline (t1) to end of treatment (t2, 12wk), and at 12 weeks (t3) and 24 weeks (t4) after end of treatment, significant differences were noted only for the mEFAP and SSQOL scores. The change in the average scores for both mEFAP and SSQOL occurred between t1 and t2, followed by relative stability thereafter. CONCLUSIONS: There was no evidence of a motor relearning effect on lower limb motor impairment in either the PNS or usual-care groups. However, both the PNS and usual-care groups demonstrated significant improvements in functional mobility and quality of life during the treatment period, which were maintained at 6-month follow-up.

Crustaceans from bitumen clast in Carboniferous glacial diamictite extend fossil record of copepods.

Copepod crustaceans are extremely abundant but, because of their small size and fragility, they fossilize poorly. Their fossil record consists of one Cretaceous (c. 115 Ma) parasite and a few Miocene (c. 14 Ma) fossils. In this paper, we describe abundant crustacean fragments, including copepods, from a single bitumen clast in a glacial diamictite of late Carboniferous age (c. 303 Ma) from eastern Oman. Geochemistry identifies the source of the bitumen as an oilfield some 100-300 km to the southwest, which is consistent with an ice flow direction from glacial striae. The bitumen likely originated as an oil seep into a subglacial lake. This find extends the fossil record of copepods by some 188 Ma, and of free-living forms by 289 Ma. The copepods include evidence of the extant family Canthocamptidae, believed to have colonized fresh water in Pangaea during Carboniferous times.

A pilot study to investigate the feasibility of electrical stimulation to assist gait in Parkinson's disease.

Objectives. This study aims to investigate the effect of functional electrical stimulation (FES) on gait in people with Parkinson's disease. Materials and Methods. Seven subjects with idiopathic Parkinson's disease received single-channel electrical stimulation for eight weeks to the common peroneal nerve to improve heel strike and provide sensory stimulus during the swing phase of gait. Stride length, time, and number of steps to complete a 20-m walk and distance completed in 3 min were assessed. Episodes of freezing and incidence of falls were recorded. Statistical analysis of the walking test data was analyzed using the nonparametric Wilcoxon signed ranks test. Results. An immediate improvement was demonstrated with FES on distance and average stride length during a 3-min walk during the treatment period but not on number of steps and walking speed during a 20-m walk. A training effect was observed for all parameters of gait measured over the eight-week treatment period, which was mostly maintained four weeks after treatment was stopped. Fewer falls and episodes of freezing occurred during the treatment period. The number of falls returned to pretreatment levels when treatment was stopped. Conclusions. This study has shown that FES can improve some parameters of gait over an eight-week period of use with a carryover effect that is maintained without stimulation during that time and an immediate reduction in the frequency of falls. An immediate effect of FES was demonstrated over a 3-min walk but not over a 20-m walk. Improvements in gait largely persisted on reassessment four weeks after stopping use of FES although the frequency of falls returned to pretreatment levels. A larger study is required to support these findings, to understand the mechanisms of the effects of electrical stimulation on gait and to identify those most likely to benefit from it.

Walking on an uneven surface: the effect of common peroneal stimulation on gait parameters and relationship between perceived and measured benefits in a sample of participants with a drop-foot.

Objectives. To examine the effect of using a common peroneal stimulator on an even and an uneven surface, and to compare measures with perceived response to stimulation. Method. Participants had a drop-foot caused by a stroke (N = 13) or multiple sclerosis (N = 7) and had used a common peroneal stimulator for > 3 months prior to the study. Walking speed and physiological cost index (PCI) were recorded under four conditions: with and without stimulation over an even and an uneven surface. Participants also completed a questionnaire. Results. A statistically significant increase in walking speed and decrease in PCI was identified when the stimulator was used. There was a trend to greater improvement on the uneven compared to the even surface. A correlation between perceived benefit of stimulation and a measured decrease in PCI was detected. Conclusion. Stimulation may be particularly beneficial for the more difficult task of walking on an uneven surface. Perceived benefit was related to a reduction in effort of walking, not in increased speed.

Effectiveness of electric stimulation of the vastus medialis muscle in the rehabilitation of patients after total knee arthroplasty.

OBJECTIVE: To investigate the possible effect of electric muscle stimulation (EMS) of the vastus medialis on the walking speed, Hospital for Special Surgery (HSS) knee score, and Physiological Cost Index (PCI) of patients during rehabilitation after total knee arthroplasty (TKA). DESIGN: Prospective, randomized controlled trial. SETTING: Various departments at a district general hospital in the United Kingdom. PARTICIPANTS: Thirty patients with unilateral osteoarthritis of the knee admitted for elective TKA were randomly assigned to 1 of 2 groups (15 per group): control and treatment. Both groups received standard physical therapy. The treatment group also received EMS of the vastus medialis. INTERVENTION: EMS (40Hz, 300micros) of the vastus medialis muscle for 4 hours a day, starting on postoperative day 2, over the first 6 postoperative weeks. MAIN OUTCOME MEASURES: Changes in walking speed, HSS knee score, and effort of walking as measured by the PCI. RESULTS: A statistically significant increase in walking speed was observed in the treatment group in relation to the control group at both 6 weeks (P=.0002) and 12 weeks (P<.0001) postoperatively. No statistically significant difference was observed in relation to the PCI or the HSS knee score variables. CONCLUSIONS: Application of EMS after TKA resulted in a statistically significant improvement in patients' walking speed. There was also a carry-over effect after the discontinuation of treatment.

New leptin receptor mutations in mice: Lepr(db-rtnd), Lepr(db-dmpg) and Lepr(db-rlpy).

Three new spontaneous recessive mouse mutations in the leptin receptor gene (Lepr), Lepr(db-rtnd), Lepr(db-dmpg) and Lepr(db-rlpy), originated in the CBA/J (CBA), B10.D2-H8(b)(57N)/Sn (B10) and NU/J strains, respectively. Lepr(db-rtnd) and Lepr(db-dmpg) were maintained on C57BL/6J (B6), resulting in congenic lines of B6.CBA-Lepr(db-rtnd) and B6.B10-Lepr(db-dmpg). Lepr(db-rtnd) was also maintained on CBA post F1 generation of a cross between the B6 and the CBA, generating the congenic line CBA.B6CBA-Lepr(db-rtnd). Lepr(db-rlpy) was maintained as a coisogenic strain. The aims of this study were to determine the molecular bases for these new Lepr mutations and to characterize the new mutant stocks, with respect to obesity and diabetes. Mutations were analyzed by Southern blot analysis, reverse transcriptase-polymerase chain reaction and sequencing. Body weights and plasma glucose and insulin levels were measured, and the histology of the pancreas was carried out. Lepr(db-rtnd) contained one G deletion in exon 4 of Lepr, introducing a frameshift and premature termination. Lepr(db-dmpg) had a deletion in the extracellular domain of LEPR: Lepr(db-rlpy) exhibited a large DNA deletion, leading to a complete lack of LEPR: All three mutations led to morbid obesity and diabetes. It is noteworthy that Lepr(db-rtnd) caused milder hyperglycemia accompanied by higher plasma and pancreatic insulin contents on B6 compared to that on CBA backgrounds. In summary, we discovered three new mutations of Lepr, providing new mouse models for obesity and diabetes. Furthermore, our mutant stocks will be useful in elucidating the effects of the genetic background on the Lepr mutations and in testing the specificity of antibodies to LEPR.