Summary of findings 2. Botulinum toxin A (with and without casting) compared with placebo (with and without casting) for spasticity in people with traumatic brain injury.

Botulinum toxin A (with and without casting) compared with placebo (with and without casting) for spasticity in people with traumatic brain injury
Patient or population: adults with traumatic brain injury with spasticity in their arms (1 study) or calves (1 study) Settings: rehabilitation/neurology clinics or acute general hospital, in Europe or the UK Intervention: botulinum toxin A × 1 dose (500/1000 U) or botulinum toxin A × 1 dose of 200 U + serial casting Comparison: placebo (± casting)
Outcomes	Results and conclusions	No of participants (studies)	Quality of the evidence (GRADE)
Spasticity at 4‐12 weeks (measured by both Modified Ashworth Scale, 0‐5, at 12 weeks and Tardieu Scale, 0‐5, at 4 weeks)	We are uncertain about the effect of botulinum toxin A (± casting) vs placebo (± casting) on spasticity.1	47 (2)2	⊕⊝⊝⊝ Very low3
Adverse events	We are uncertain about the effect of botulinum toxin A (± casting) vs placebo (± casting) on adverse events.4	47 (2)2	⊕⊝⊝⊝ Very low5
Sensory functions and pain	No study measured this outcome.
Neuromusculoskeletal and movement‐related functions at 12 weeks (measured by ankle dorsiflexion)	We are uncertain about the effect of botulinum toxin A (± casting) vs placebo (± casting) on adverse events.6	47 (2)2	⊕⊝⊝⊝ Very low7
General tasks and demands	No study measured this outcome.
Mobility	No study measured this outcome.
Self‐care	No study measured this outcome.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹Gracies 2015 reported that "with abobotulinumtoxinA, the angle of catch (XV3 of the Tardieu Scale) improved in finger (+35 degree), elbow (+22 degree) and wrist (+12 degree) flexors" but no further outcome data were provided. For Verplancke 2005, we calculated the between‐group difference in spasticity (as measured by the Modified Ashworth Scale) as mean difference 0.30 (95% confidence interval ‐0.87 to 1.47).

²Included studies: Gracies 2015; Verplancke 2005.

³Downgraded four times due to: risk of bias concerns for both studies (downgraded twice, because either insufficient information about random sequence generation and allocation concealment, in one study, and potential selective outcome reporting in both studies), indirectness (one study included mixed traumatic brain injury and stroke populations, and measured spasticity using the Modified Ashworth Scale) and a high likelihood of publication bias in this area.

⁴In the main trial of Gracies 2015 (in which the traumatic brain injury population was a part (9.5%)) the most common botulinum toxin A‐related adverse event was 'mild muscle weakness' and investigators reported that all adverse events were mild or moderate only. In Verplancke 2005, botulinum toxin A was reported to be well tolerated, with only one participant with 'flu‐like' symptoms (i.e. shivering, sweating and fever). In groups who received casting (either alone, or in addition to botulinum toxin A), 41% to 50% developed 'minor' skin damage. Overall, 90.9% of those resolved spontaneously or with therapeutic dressing.

⁵Downgraded three times due to: risk of bias concerns for both studies (downgraded twice, because in one study there was insufficient information about random sequence generation and allocation concealment, and in both studies the adverse events data was reporting in percentages only) and a high likelihood of publication bias in this area.

⁶Verplancke 2005 reported between‐group differences in ankle dorsiflexion, finding no differences between groups in a one‐way ANOVA (casting + placebo versus casting + botulinum toxin A: P = 0.11). However, they did not report any summary statistics for this, or any baseline scores.

⁷Downgraded four times due to: risk of bias concerns for both studies (downgraded twice, because either insufficient information about random sequence generation and allocation concealment, in one study, and potential selective outcome reporting in both studies), indirectness (one study included mixed traumatic brain injury and stroke populations) and a high likelihood of publication bias in this area.