Objective detection of subtle freezing of gait episodes in Parkinson's disease

Freezing of gait (FOG) is a clinically defined phenomenon of Parkinson's disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes. We included 10 PD patients with FOG, 10 PD patients without FOG, and 10 controls. Subjects walked on a motorized treadmill while avoiding unexpectedly appearing obstacles. Treadmill walking was videotaped, and FOG episodes were identified by two independent experts. Gait was also analyzed using detailed kinematics. Knee joint signals were processed using time–frequency analysis with combinations of sliding fast Fourier transform and wavelets transform. Twenty FOG episodes occurred during treadmill walking in 5 patients (all with clinically certified FOG), predominantly in relation to obstacle avoidance. FOG was brief when it occurred just before or after obstacle crossing and was characterized by short, rapid steps. Frequency analysis showed a typical qualitative pattern: before the FOG episode an increase in dominant frequency in the 0 to 3 Hz band (festination), followed by decreased power in 0 to 3 Hz band and an increased power in the 3 to 8 Hz band during the FOG episode. This pattern led to an increased FOG index as a qualitative measure. These approaches detected even very brief FOG with acceptable sensitivity (75–83%) and specificity (>95%). We conclude that time–frequency analysis is an appropriate approach to detect brief and subtle FOG episodes. Future work will need to decide whether this approach can support or even replace expert clinical opinion. © 2010 Movement Disorder Society     

Activation of plasminogen by tissue plasminogen activator on normal and thrombasthenic platelets: effects on surface proteins and platelet aggregation

Tissue plasminogen activator (TPA) converts plasminogen to plasmin within the fibrin clot, thus localizing activation of fibrinolysis. To determine the extent to which platelets promote activation of plasminogen by TPA, we studied the interaction of TPA and plasminogen with unstimulated platelets. Normal washed platelets incubated in the presence of physiologic concentrations of plasminogen (180 micrograms/mL) and TPA (20 ng/mL) failed to generate plasmin activity. In contrast, incubation of platelets with TPA concentrations achieved during thrombolytic therapy (40 to 800 ng/mL) produced a tenfold to 50- fold increase in plasmin activity. After exposure to plasminogen and 200 ng/mL of TPA for one hour, platelets failed to agglutinate in the presence of ristocetin. Incubation of platelets suspended in autologous plasma with 400 ng/mL of TPA for one hour also inhibited ristocetin- induced agglutination. Exposure of platelets to plasminogen and increasing concentrations of TPA correlated with a decrease in glycoprotein Ib (GPIb) and an increase in glycocalicin, as shown by immunoblotting. The glycoprotein IIb/IIIa (GPIIb/IIIa) complex and a 250,000-dalton protein also disappeared from washed platelets after incubation with plasminogen and 200 ng/mL of TPA for one hour. These platelets failed to aggregate in the presence of adenosine diphosphate (ADP) or gamma thrombin, although aggregation in response to calcium ionophore A23187 and arachidonic acid remained intact. However, aggregation in response to all four agonists was normal when platelets were incubated with TPA in the presence of autologous plasma. Platelets from a patient with Glanzmann's thrombasthenia also generated plasmin in the presence of TPA. Hydrolysis of GPIb and inhibition of ristocetin- induced agglutination occurred to a lesser extent with these platelets than with control platelets. We conclude that platelets provide a surface for activation of plasminogen by pharmacologic amounts of TPA. Plasmin generation leads to degradation of GPIb and decreased ristocetin-induced agglutination in normal and thrombasthenic platelets, as well as degradation of GPIIb/IIIa in normal washed platelets and inhibition of ADP and gamma thrombin-induced aggregation. These findings suggest that pharmacologic concentrations of TPA may cause platelet dysfunction due to plasmin generation on the platelet surface.     

Dutch Physiotherapy Guidelines for Low Back Pain

Many guidelines for the management of low back pain in primary care have been published during recent years, but guidelines for physiotherapy do not yet exist. Therefore, physiotherapy guidelines have been developed, reflecting the consequences of the current state of knowledge of effective and appropriate physiotherapy for low back pain. They aim to improve the efficiency and effectiveness of physiotherapeutic care for patients with low back pain.The guidelines were constructed on the basis of the phases of the physiotherapy process, using the Dutch method of developing physiotherapy guidelines. Scientific evidence of systematic reviews was used as the basis for the recommendations. A computerised literature search of Medline, Cinahl, the Cochrane Database of Systematic Reviews and the Database of the Dutch National Institute of Allied Health Professions was conducted to identify relevant systematic reviews. If no evidence was available, consensus between experts was obtained.The guidelines were pilot tested among one hundred physiotherapists and reviewed by an external multi-disciplinary panel.The guidelines recommend that the diagnostic process should focus on disability and participation problems resulting from back pain. The treatment should consist of an active approach, in which the patients learn to take control over their back pain. For patients with a normal course, where activities and participation gradually increase, reassurance, adequate information and advice to stay active are the most important recommendations. For patients with an abnormal course, where activities and participation do not increase, exercise therapy should also be provided, with a behavioural approach if necessary.These are the first national physiotherapy guidelines for low back pain. The recommendations are largely in line with other primary care guidelines for low back pain. Implementation will be a major challenge for the near future.     

Abstract 17: A novel microanalytical technique for assaying soft tissue demonstrates significant quantitative biochemical differences in 3 clinically distinct groups: normal, latent, and active.

Objectives: To determine (1) whether a novel microdialysis needle can successfully sample the biochemical milieu of trigger point 1 (TP1) in the upper trapezius muscle in healthy subjects and (2) whether there are measurable differences among those with symptoms and physical findings related to myofascial trigger points (MTrPs). Design: Prospective, controlled trial. Setting: Biomedical research hospital. Participants: 3 subjects were selected based on history and physical examination for 3 groups (N=9): group 1, normal (no neck pain, no MTrP); group 2, latent (no neck pain, MTrP present); and group 3, active (neck pain, MTrP present). Intervention: Pressure algometry was performed at TP1 to determine pain pressure threshold (PPT). Samples were obtained continuously with a microdialysis needle at regular intervals, starting with needle insertion, elicitation of a local twitch response, and then posttwitch. Main Outcome Measures: PPT and levels of pH, substance P, calcitonin gene-related peptide (CGRP), bradykinin, norepinephrine, tumor necrosis factor-alpha (TNF_α), and interleukin-1β (IL-1β). Results: The active group had a lower PPT (P<.08). Overall, the amount of substance P, CGRP, bradykinin, norepinephrine, TNF_α, and IL-1β was significantly higher in the active group than in the other 2 groups (P<.01). Overall, pH was significantly lower in the active group than in the other 2 groups (P<.03). At 5 minutes, peak levels of substance P and CGRP differed significantly in all 3 groups (3>2>1, P<.02). Conclusions: This technique recovered extremely small quantities (<0.5μL) of very small substances (molecular weight, <100kd) directly from soft tissue. There were significant differences in the levels of pH, substance P, CGRP, bradykinin, norepinephrine, TNF_α, and IL-1β in those subjects with an active MTrP (symptoms, MTrP present) compared with subjects with a latent MTrP (no symptoms, MTrP present) and normal subjects (no symptoms, no MTrP).     

Poster 20: Effects of a cognitive training program on outcomes in extended acute inpatient medical rehabilitation for patients with cardiac disease

Objectives: To test the hypotheses that (1) a structured learning environment and computer-based cognitive training will improve cognition in elderly, extended acute (phase 1B) medical inpatients admitted for deconditioning secondary to cardiac disease, who demonstrate cognitive deficits on admission; and (2) a change in cognition will lead to improved functional outcomes. Design: Experimental, prospective, randomized, single-factor, pretest-posttest design. Setting: Phase 1B inpatient medical rehabilitation unit using a multidisciplinary approach. Participants: 50 patients (47 completed the study) admitted to a phase 1B inpatient medical rehabilitation unit who met study inclusion criteria (Mini-Mental State Examination score, <25; >1wk length of stay [LOS], cardiac diagnosis) were randomly assigned to a cognitive training group (experimental, n=25) or standard treatment (control, n=22) group. Interventions: Groups received 3 to 6 hours of daily standard therapy. The experimental group also received computer-based cognitive training sessions 3 times/wk, 20 min/session, and a morning and evening group session designed to improve memory and organization skills. Main Outcome Measures: For hypothesis 1, cognitive portion of the FIM™ instrument. For hypothesis 2, LOS, falls, number of home services on discharge, discharge placement, total and motor FIM scores, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Results: There were no significant differences in baseline characteristics. The experimental group showed a significantly greater percentage improvement for the cognitive portion of the FIM (23.6%±18.4% vs 11.8%±17.2%, P=.035). LOS, falls, home services, discharge placement, total FIM, motor FIM, and 7 of 8 of the SF-36 subscales did not differ between the groups. The control group showed a significantly greater percentage improvement on the physical functioning subscale of the SF-36 (130.0%±67.1% vs 83.3%±66.5%, P=.008). Conclusions: The structured learning environment and computer-based training program showed improvements in cognition, as measured by the cognitive portion of the FIM. However, there were no differences in functional outcomes.     

Small-molecule nociceptin receptor agonist ameliorates mast cell activation and pain in sickle mice

Treatment of pain with morphine and its congeners in sickle cell anemia is suboptimal, warranting the need for analgesics devoid of side effects, addiction and tolerance liability. Small-molecule nociceptin opioid receptor ligands show analgesic efficacy in acute and chronic pain models. We show that AT-200, a high affinity nociceptin opioid receptor agonist with low efficacy at the mu opioid receptor, ameliorated chronic and hypoxia/reoxygenation-induced mechanical, thermal and deep tissue/musculoskeletal hyperalgesia in HbSS-BERK sickle mice. The antinociceptive effect of AT-200 was antagonized by SB-612111, a nociceptin opioid receptor antagonist, but not naloxone, a non-selective mu opioid receptor antagonist. Daily 7-day treatment with AT-200 did not develop tolerance and showed a sustained anti-nociceptive effect, which improved over time and led to reduced plasma serum amyloid protein, neuropeptides, inflammatory cytokines and mast cell activation in the periphery. These data suggest that AT-200 ameliorates pain in sickle mice via the nociceptin opioid receptor by reducing inflammation and mast cell activation without causing tolerance. Thus, nociceptin opioid receptor agonists are promising drugs for treating pain in sickle cell anemia.     

‘I've Been Walking on Eggshells All My Life’: Fibromyalgia Patients' Narratives About Experienced Violence and Abuse

According to earlier research, the prevalence of violence and abuse in the life history of patients with chronic widespread pain and fibromyalgia seems to be high in comparison with other pain patients and healthy controls. The purpose of the present study was to explore how experiences of violence and abuse are expressed and reflected on and how the causes and consequences of violence are interpreted by female patients with a long history of fibromyalgia. The data were drawn from narrative interviews of 11 women who had earlier participated in a fibromyalgia‐specific rehabilitation course. The findings are presented through three main themes: loss of self‐esteem, physical and mental bruises, and loss of womanhood. The onset of fibromyalgia was perceived as an inevitable result of physical or mental trauma. In conclusion, the narrated life stories indicated that violence is still hidden behind a wall of silence and non‐interference in our society. The devastating mental and physical consequences of violence in different forms may be carried by the individual for years, even decades. Understanding any exposure to violence that a patient has endured may help healthcare professionals to understand the individual's health behaviour and any possible reluctance to undergo treatment and rehabilitation. Copyright © 2015 John Wiley & Sons, Ltd.