Imaging spasticity

Are you a baclofen zombie? #MSBlog #MSResearch

"This study simply shows that MSers are more likely to have spasticity if they have MRI lesions loads and if those lesions are in a pathway that affects the nerve fibres that control motor function. This is what we expect. However, it stresses the link between the number of MRI lesions, or burden of disease, and spasticity. The corollary of  this is if can prevent these lesions from forming the first place you will prevent the damage to the motor pathway and spasticity developing."
"Spasticity is when any passive fast movement of the leg is resisted by the muscles contracting. If severe spasticity can cause spasms and limb jerks. This is a particular problem at night when you are asleep; limb jerks tend to keep you awake at night. When spasticity is bad it often associated with pain and discomfort in the muscles. Spasticity is made worse by pressure and ill fitting orthotics and shoes; please check to make sure this is not a problem. In addition, spasticity typically gets worse with infections and when you are tired."

Are you a baclofen zombie?

"We have many drugs for treating spasticity, all of them cause sedation and can make cognitive impairment worse. Baclofen the most commonly prescribed anti-spastic agent has a short half-life (time it takes for the concentration in the blood to halve itself) and hence wears off too quickly. This is why you need to take it 3 or 4 times a day and in some circumstance more often. Because of the problems with baclofen, and other antispastic agents, MouseDoctor 1 & 2, have been working hard to address this unmet need. They have discovered a class of agents that works in the periphery and does not cause sedation in our animal model of MS. To commercialise these compounds they have formed a University spin-off company called Canbex. The first-in-man or phase 1 studies are about to start. So please watch this space if you are interested to see if this gets through the pipeline."

"Is the Canbex business model flawed? If we treat MS early and actively with highly-effective therapies and prevent or delay secondary progressive MS we may reduce the market for Canbex's products substantially. Do you think they we have a conflict of interest?"

Bertoni et al. Neuroimaging assessment of spasticity developed after acquired brain injuries and multiple sclerosis. Neuroradiol J. 2012;25(3):311-7. 

Background: This study evaluated whether different imaging techniques correlate with specific variables routinely used to grade the types and complexities of people with conditions in neurorehabilitation services and their clinical outcomes, and if there are radiological patterns, topography or distribution of the lesions correlated to spasticity. 

Subjects & Methods: The cohort studied included 75 patients, 38 MSers and 37 patients with acquired brain injuries (ABI) referred to the neurorehabilitation department from April 2009 to March 2010. Data included age, gender, diagnoses, complications, spasticity, length of stay, Rehabilitation Complexity Scale (RCS) and Northwick Park Dependency (NPDS) scores on admission and discharge. Forward stepwise multiple regressions were performed considering Spasticity as dependent and considering NPDS, RCS on admission and discharge, age, gender and length of stay as independent variables. Standardized intra-axial lesions in those with spasticity were fused with standardized axial DTIs from normal controls obtained under 3 T and 1.5 T MRI scanners.

Results: Spasticity was present in 36 patients. Regression was found between spasticity and all the other variables with r = 0.42, r(2) = 0.17, p < 0.01. Residuals were acceptable. If the same is calculated excluding MS patients the results are higher with: r = 0.59, r(2) = 0.35, p < 0.003. In MS subjects, spasticity appeared if lesions affected pyramidal tracts, callosal radiations extensively or brainstem. 

Conclusions: Findings suggest that NPDSa and discharge and RCSd are higher in those developing spasticity. No obvious correlation between spasticity and RCSa was found. Subjects with MS are more likely to develop spasticity especially if the lesions are numerous and affect the corticospinal tracts, callosal radiations extensively or brainstem. In patients with ABI lesions affecting pyramidal tracts, pericommissural areas and optochiasmatic cisterns seem more likely to develop spasticity.

To read more about Canbex:

25 Apr 2013
Canbex Therapeutics Ltd has completed a £2.1m ($3.2m) fundraising round that will enable the Company to complete the early development of its lead candidate for the treatment of spasticity in multiple sclerosis (MS).

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