ABSTRACT
Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.
ABSTRACT
OBJECTIVE: To find more accurate indices that could affect decisions in spasticity treatment by investigating the relation between ultrasonographic, electromyographic, and clinical parameters of the gastrocnemius muscle in adults with spastic equinus after stroke. DESIGN: Observational study. SETTING: University hospitals. PARTICIPANTS: Chronic patients with stroke with spastic equinus (N=43). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ultrasonographic features were spastic gastrocnemius muscle echo intensity, muscle thickness, and posterior pennation angle of the gastrocnemius medialis (GM) and gastrocnemius lateralis (GL) in both legs. Electromyographic evaluation included compound muscle action potentials (CMAPs) recorded from the GM and GL of both legs. Clinical assessment of the spastic gastrocnemius muscle was performed with the Modified Ashworth Scale (MAS) and by measuring ankle dorsiflexion passive range of motion (PROM). RESULTS: Spastic muscle echo intensity was inversely associated with proximal (GM and GL: P=.002) and distal (GM and GL: P=.001) muscle thickness, pennation angle (GM: P< .001; GL: P=.01), CMAP (GM: P=.014; GL: P=.026), and ankle PROM (GM: P=.038; GL: P=.024). The pennation angle was directly associated with the proximal (GM and GL: P< .001) and distal (GM: P=.001; GL: P< .001) muscle thickness of the spastic gastrocnemius muscle. The MAS score was directly associated with muscle echo intensity (GM: P=.039; GL: P=.027) and inversely related to the pennation angle (GM and GL: P=.001) and proximal (GM: P=.016; GL: P=.009) and distal (GL: P=.006) muscle thickness of the spastic gastrocnemius. CONCLUSIONS: Increased spastic muscle echo intensity was associated with reduced muscle thickness, posterior pennation angle, and CMAP amplitude in the gastrocnemius muscle. Building on previous evidence that these instrumental features are related to botulinum toxin response, these new findings may usefully inform spasticity treatment decisions.
