Botulinum toxin A dosage: autonomic function as a measure of side effects' SIR-Treatment of spasticity in cerebral palsy (CP) with botulinum toxin A (BTX-A) is limited by the escape of the toxin from the muscle causing local and distant side effects. 1 This study aimed to increase BTX-A dose (over 30 units/kg for Dysport) safely. We noted signs of autonomic spread of the toxin following injection of a range of doses (18-44 units/kg) in 30 patients. In previous work on BTX-A treatment we have looked for changes in resting heart rate, change in heart rate on standing, change in blood pressure on standing, and pupilometry. None of these parameters revealed a statistically significant relationship with BTX-A dose 2 , and so in this study cardiac variability was chosen. Our hypothesis was that BTX-A might reduce parasympathetic activity and, therefore, cardiac variability.The Southern Derbyshire Acute Hospitals NHS Trust's ethics committee approved the study, and patients and controls were included after they or their caregivers gave informed consent. All patients attending our clinic for lower limb BTX-A injections were invited to participate. The healthy siblings of participants were invited to be controls. The control group was composed of six males and eight females aged between 8 and 11 years (mean 11y 4mo, SD 2mo). The patient group included 22 males and eight females aged between 3 and 15 years (mean 8y 7mo, SD 4mo). Nine patients had quadriplegic CP and 21 had diplegic CP. Gross Motor Function Classification System (GMFCS) levels were: level II, n=3; level III, n=12; level IV, n=9; level V, n=6. A 6-hour overnight electrocardiogram (ECG) recording was made for each patient before and 14 to 21 days after BTX-A treatment, and the recordings were compared with those of 14 untreated siblings. The ECGs were analyzed and the mean of the standard deviations of duration of R-R (beat-tobeat) interval (SDNN [NN equates to one cardiac cycle]) was calculated. The posttreatment SDNN divided by the pretreatment SDNN gave the autonomic ratio (AR).The 14 untreated, normal controls had a median AR of 1.12 (interquartile range 0.94-1.22). Median AR at a standard dose of BTX-A (18-30 units/kg) was 1.02 (range 0.64-1.10) and at a high dose (31-44 units/kg) was 0.88 (range 0.79-1.08). Results were compared using the Mann-Whitney U test. There was no statistical significance between the control group and the conventionally dosed group (p=0.06) or between the conventionally dosed group and the high dose group. When all those treated with BTX-A were compared with controls there was a small statistical difference between them (p=0.02); when the control group was compared with the high dose group this difference was also statistically significant (p=0.03). When BTX-A dose was plotted against AR there was no significant correlation (r=-0.13, p=0.42). Clinically, only one child had distant side effects which lasted for 6 weeks; he had the lowest AR in the study group (0.33) after receiving 37 units/kg BTX-A.These results offer further re...

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