Ilona A. Barash

STRUCTURAL AND FUNCTIONAL CHANGES IN SPASTIC SKELETAL MUSCLE

This review summarizes current information regarding the changes in structure or function that occur in skeletal muscle secondary to spasticity. Most published studies have reported an increase in fiber size variability in spastic muscle. There is no general agreement regarding any shift in fiber type distribution secondary to spasticity. Mechanical studies in whole limbs as well as in isolated single cells support the notion of an intrinsic change in the passive mechanical properties of muscle after spasticity in addition to the more widely reported neural changes that occur. Evidence is presented for changes within both the muscle cell and extracellular matrix that contribute to the overall changes in the tissue. Taken together, the literature supports the notion that, although spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this problem. Muscle Nerve 29: 615–627, 2004

Asynchronous functional, cellular and transcriptional changes after a bout of eccentric exercise in the rat

Thirty eccentric contractions (ECs) were imposed upon rat dorsiflexors (n= 46) by activating the peroneal nerve and plantarflexing the foot ≈40 deg, corresponding to a sarcomere length change over the range 2.27‐2.39 μm for the tibialis anterior and 2.52‐2.66 μm for the extensor digitorum longus. Animals were allowed to recover for one of 10 time periods ranging from 0.5 to 240 h, at which time muscle contractile properties, immunohistochemical labelling and gene expression were measured. Peak isometric torque dropped significantly by ≈40 % from an initial level of 0.0530 ± 0.0009 Nm to 0.0298 ± 0.0008 Nm (P < 0.0001) immediately after EC, and then recovered in a linear fashion to control levels 168 h later. Immunohistochemical labelling of cellular proteins revealed a generally asynchronous sequence of events at the cellular level, with the earliest event measured being loss of immunostaining for the intermediate filament protein, desmin. Soon after the first signs of desmin loss, infiltration of inflammatory cells occurred, followed by a transient increase in membrane permeability, manifested as inclusion of plasma fibronectin. The quantitative polymerase chain reaction (QPCR) was used to measure transcript levels of desmin, vimentin, embryonic myosin heavy chain (MHC), myostatin, myoD and myogenin. Compared to control levels, myostatin transcripts were significantly elevated after only 0.5 h, myogenic regulatory factors significantly elevated after 3 h and desmin transcripts were significantly increased 12 h after EC. None of the measured parameters provide a mechanistic explanation for muscle force loss after EC. Future studies are required to investigate whether there is a causal relationship among desmin loss, increased cellular permeability, upregulation of the myoD and desmin genes, and, ultimately, an increase in the desmin content per sarcomere of the muscle.

Stress-dependent and -independent expression of the myogenic regulatory factors and the MARP genes after eccentric contractions in rats

The relationship between muscle mechanical conditions and gene expression was investigated by varying both stress and contraction mode imposed upon rat dorsiflexors (n= 25), activating them at high or low frequencies (150 Hz or 40 Hz) either eccentrically or isometrically. Muscle physiological, immunohistochemical and gene expression changes were then measured 24 h after the exercise bout. Peak stress was the best predictor of muscle injury, independent of contraction mode (i.e. eccentric or isometric). When peak stresses were matched, no physiological or immunohistochemical differences were detected between isometric and eccentric contractions. The expression of certain myogenic regulatory and muscle ankyrin repeat protein (MARP) genes (myoD, myogenin, MLP and CARP) depended both on peak muscle stress achieved during contraction and contraction mode. In contrast, Arpp/Ankrd2 was dramatically upregulated only by eccentric contractions, but not by isometric contractions, even though the stress level of the eccentric contractions varied over a three‐fold range and overlapped with that of the isometric group. The role that Arpp/Ankrd2 upregulation plays in the biological response to eccentric contraction remains to be determined, as does the control mechanism whereby the expression of certain genes (such as myoD, myogenin, MLP and CARP) is sensitive to muscle stress while another (Arpp/Ankrd2) is sensitive only to contraction mode.

Characteristics of Spacer Device Use by Patients with Asthma and COPD

OBJECTIVE Spacer devices (SD) in conjunction with metered dose inhalers (MDI) have been shown to be as effective as saline nebulizers for the delivery of beta-agonists. A preliminary study suggests that SDs are not consistently used. The purpose of this study was to investigate patterns of SD ownership and use to identify potential targets for future educational efforts to increase ownership and use of SD. METHODS Cross-sectional convenience sample survey of patients presenting to an academic Emergency Department (ED) with a history of asthma/COPD (chronic obstructive pulmonary disease). Informed consent was obtained. Survey data included demographics, association with a primary care physician (PCP), SD ownership, patterns of use, opinions of efficacy about SD and disease severity assessed by duration of asthma/COPD, prior ED visits, hospitalizations, and history of prior intubation. Patterns of use are described and univariate and multivariate analyses were used to identify factors associated with SD ownership. RESULTS Of the 313 patients, 55.9% were female, the mean age was 46.0 years (standard deviation 14.7), 54.3% were white, and 143 patients (45.7%) reported owning a SD. A total of 36.4% reported a prior hospitalization for their condition and 24% reported a history of being intubated. Less than half of patients presenting with asthma or COPD exacerbation that reported owning a SD used it the day of presentation to the ED. Logistic regression identified having a PCP and a history of prior hospitalization for asthma/COPD as factors independently associated with SD ownership (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.7 and OR 2.2, CI 1.3-3.5, respectively). CONCLUSION A majority of patients with asthma/COPD do not own a SD. These data suggest that there is significant opportunity for educational efforts directed at a broad range of asthma/COPD patients in hopes of increasing ownership and use of SD.

Bilateral subdural hematomas after lumboperitoneal shunt placement.

BACKGROUND Lumboperitoneal shunts are commonly placed as treatment for a variety of conditions, and complications can be significant. OBJECTIVES We discuss a rare complication of these shunts, namely bilateral non-traumatic subdural hematoma formation. CASE REPORT A patient with a normal neurologic examination but severe nausea, weight loss, and dehydration presented 2 weeks after lumboperitoneal shunt placement for cryptococcal meningitis, and was found to have bilateral subdural hematomas. CONCLUSIONS Physicians should be aware of this potentially devastating complication of shunt placement so that prompt and appropriate treatment can be initiated.