Botulinum toxin injection for post‐stroke spasticity

Introduction: The aim of this study was to evaluate test feasibility, validity, and reproducibility of the rate of force development scaling factor (RFD‐SF) for the hip muscles. Methods: Feasibility was assessed as the testing compliance, validity as the ability to compute the RFD‐SF from a linear regression, and reproducibility with a test–retest design in 20 healthy subjects. Reliability and agreement (reproducibility) were evaluated using intraclass correlation coefficient (ICC_3,1) and percent standard error of measurement (SEM), respectively. Results: The RFD‐SF testing protocol was completed successfully by all subjects, although the analysis had to be modified for hip rotators. Reliability was high (ICC_3,1 > 0.70) for all muscles except hip abductors (ICC_3,1 = 0.69) and internal rotators (ICC_3,1 = 0.58). Agreement was high for all muscles (SEM < 10%). Conclusions: Hip adductor, flexor, and external rotator RFD‐SF can be evaluated with confidence, provided the analysis is modified for external rotators, whereas hip abductor and internal rotator RFD‐SF assessment is not recommended. Muscle Nerve 50: 932–938, 2014     

Intracellular distribution of differentially phosphorylated dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A)

The gene encoding dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age‐associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell‐compartment‐specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two‐dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5–6.5 in the nucleus, 7.2–8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate‐affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment‐specific functions of DYRK1A may depend on its phosphorylation pattern. © 2013 Wiley Periodicals, Inc.     

When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis

Supraspinal processes in humans can have a top‐down enhancing effect on nociceptive processing in the brain and spinal cord. Studies have begun to suggest that such influences occur in conditions such as fibromyalgia (FM), but it is not clear whether this is unique to FM pain or common to other forms of chronic pain, such as that associated with osteoarthritis (OA). We assessed top‐down processes by measuring anticipation‐evoked potentials and their estimated sources, just prior (< 500 ms) to laser heat pain stimulation, in 16 patients with FM, 16 patients with OA and 15 healthy participants, by using whole‐brain statistical parametric mapping. Clinical pain and psychological coping factors (pain catastrophizing, anxiety, and depression) were well matched between the patient groups, such that these did not confound our comparisons between FM and OA patients. For the same level of heat pain, insula activity was significantly higher in FM patients than in the other two groups during anticipation, and correlated with the intensity and extent of reported clinical pain. However, the same anticipatory insula activity also correlated with OA pain, and with the number of tender points across the two patient groups, suggesting common central mechanisms of tenderness. Activation in the dorsolateral prefrontal cortex was reduced during anticipation in both patient groups, and was related to less effective psychological coping. Our findings suggest common neural correlates of pain and tenderness in FM and OA that are enhanced in FM but not unique to this condition.