BOTULINUM TOXIN TYPE A FOR CONTROL OF DROOLING IN ASIAN PATIENTS WITH CEREBRAL PALSY

Yu Ching Lin, Jen Yi Shieh, Mei Li Cheng, et al. Neurology 2008;70;316 DOI 10.1212/01.wnl.0000300421.38081.7d This information is current as of October 28, 2012

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.neurology.org/content/70/4/316.full.html

Neurology is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright 2008 by AAN Enterprises, Inc. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.

Clinical/Scientific Notes

Yu Ching Lin, MD, MSc Jen Yi Shieh, MD Mei Li Cheng, MD Pei Yu Yang, MD, MSc

BOTULINUM TOXIN TYPE A FOR CONTROL OF DROOLING IN ASIAN PATIENTS WITH CEREBRAL PALSY

Drooling is a significant problem in 10 to 37% of patients with cerebral palsy.1 Excessive drooling creates major hygienic and psychosocial problems. Current medical management is unsatisfactory.1-3 Botulinum toxin type A (BoNT-A) has increasingly been used to treat drooling in neurologic disorders. 4-7 However, the optimal technique, starting dose, expected duration of effect, and relationship to certain patient characteristics remain to be clarified. The purpose of our study was to evaluate the effect of BoNT-A injection into the contralateral parotid and submandibular glands to control drooling in children with cerebral palsy, and to determine the associated side effects of this treatment. Methods. The protocol was approved by our institutional review board. Thirteen patients with cerebral palsy with severe drooling were recruited. Three methods of drooling measurement were adapted: Drooling Severity and Frequency Scale,2 saliva weight, and drooling quotient.3 Patients were randomly assigned to either an experimental or a control group. The experimental group patients received two units of Botox (Allergan)/kg body weight into one parotid and the contralateral submandibular gland under ultrasound guidance (GE 700, GE Company). In the control group, 1.50 mL saline was similarly injected. SAS software (version 8.02; SAS Institute Inc., Cary, NC) was used for statistical analysis. The alpha level was set at 0.05 for all tests. Results. Thirteen patients with cerebral palsy (mean age 14.2 1.8 years) were recruited. No significant between-group differences were demonstrated comparing patient characteristics. Outcome measurements were assessed at 1 week before injection and at 2, 4, 6, 8, 10, 12, 14, 18, and 22 weeks after the treatment. Between-group comparison revealed significant differences for Drooling Severity and Frequency Scale at 2, 4, 6, 8, and 12 weeks after injection, for saliva weight at 6 and 12 weeks after

injection, and for drooling quotient at 2, 6, 8, and 10 weeks after injection (table). Comparing the experimental group pre- and post-injection, significant improvements were noted for all three outcome measurements within 14 weeks of treatment, with the exception of Drooling Severity and Frequency Scale and drooling quotient, both at 4 weeks after BoNT-A injection. Significant difference was also noted at the longest follow-up of 22 weeks in terms of saliva weight measurement. Discussion. Behavior modification, medications, and surgical approach had been advocated for management of drooling for decades. Behavior modification techniques8 are time-consuming and have inconsistent results. Anticholinergic agents (scopolamine, benztropine, and glycopyrrolate) had been used to treat drooling but side effects are commonly intolerable.9,10 Jongerius et al.4 conducted the first trial to evaluate the effect difference of transdermal scopolamine and BoNT-A injection. Drooling improved during the period of scopolamine application as well as within 24 weeks after BoNT-A injection, with fewer side effects in BoNT-A injection. The surgical procedures for drooling include denervation of salivary glands, salivary glands excision, transposition or ligation of salivary ducts.11 Neurectomy will affect the taste and lose its benefits due to reinnervation. Salivary glands excision will cause xerostomia. Greensmith et al.12 found bilateral submandibular duct transposition and unilateral parotid duct ligation had the problem of thicker saliva and xerostomia. Although bilateral submandibular duct transposition and bilateral sublingual gland excision decreased side effects, about 20% of patients still did not have satisfactory result.12 BoNT-A injection is a promising treatment option in drooling management. A few open-label studies have reported that BoNT-A injection in the submandibular or parotid glands is effective for control of drooling in cerebral palsy.4-7 Jongerius et al.4 injected bilateral submandibular glands with Botox (average 2 U/kg) and found the

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Table

Mean differences between measurements for botulinum toxin and saline treatment groups
Mean S&F scale Mean weight p Value 0.17 No. 7 6 0.03* 7 6 0.01* 7 6 0.04* 7 6 0.05* 7 6 0.08 7 6 0.05* 7 6 0.08 7 6 0.21 7 6 0.28 7 6 Mean SD 2.86 1.24 2.45 0.90 2.05 0.76 1.56 0.93 2.15 0.55 1.38 0.81 2.24 0.78 1.26 0.71 2.04 1.14 1.58 0.73 2.11 1.11 1.40 0.59 1.87 0.56 1.10 0.77 1.95 0.87 1.49 0.88 1.99 0.97 1.63 0.54 2.21 1.11 1.58 1.21 0.21 0.33 0.22 0.02* 0.26 0.16 0.02* 0.10 0.09 p Value 0.20 Mean DQ No. 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6 Mean SD 6.00 3.03 8.43 2.99 6.71 1.80 2.67 1.51 9.29 4.82 5.17 1.17 5.57 1.81 3.33 1.75 6.86 3.89 1.83 1.33 6.57 2.99 3.50 1.87 5.00 1.83 4.00 2.76 6.00 1.83 4.83 2.40 5.29 3.99 5.83 3.71 6.43 2.23 5.17 4.49 0.21 0.44 0.12 0.26 0.02* 0.01* 0.03* 0.07 0.01* p Value 0.10

Timing Baseline

Groups Control Treatment

No. 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6 7 6

Mean SD 6.86 1.21 6.17 1.33 6.29 0.76 5.33 0.82 6.71 0.95 5.17 0.75 6.29 0.76 5.00 1.26 6.29 1.11 5.00 1.26 6.14 1.57 4.83 1.47 6.43 1.72 5.00 1.55 6.57 1.81 5.33 1.51 6.43 2.07 5.50 2.07 6.43 1.81 5.67 2.25

INJ-2

Control Treatment

INF-4

Control Treatment

INJ-6

Control Treatment

INJ-8

Control Treatment

INJ-10

Control Treatment

INJ-12

Control Treatment

INJ-14

Control Treatment

INJ-18

Control Treatment

INJ-22

Control Treatment

INJ-2 (4, 6, 8, 10, 12, 14, 18, 22) indicates 2 (4, 6, 8, 10, 12, 14, 18, 22) weeks after saline or botulinum toxin injection. *Wilcoxon rank sum test, one-sided p 0.05. Mean S&F scale mean Drooling Severity and Frequency Scale; mean weight mean net saliva weight; mean DQ mean drooling quotient.

effect lasted for 6 months. Hassin-Baer et al5 treated drooling using 40 U Botox administration to the bilateral parotid glands in nine pediatric cases. Suskind and Tilton6 evaluated the effect of Botox in a sample of 17 children with cerebral palsy according to two treatment groups: 10 to 30 U into the submandibular glands or 30 U and 20 to 40 U into the submandibular and parotid glands, with more nonresponders noted in the former group. The duration of effect varied from 2 weeks to 6 months. Ellies et al7 also treated drooling in five patients by injecting both parotid and submandibular glands, with a mean duration of effect about 3 months. BoNT-A injection into bilateral submandibular and parotid glands caused thicker saliva,6 mineral and endocrine change.7 There is no consensus or guideline about the dosage of BoNT-A and which salivary glands to be injected so far. We proposed the first double-blind placebo-controlled randomized clinical trial studying the effect of unilateral injection of parotid and submandibular glands with BoNT-A for treating drooling in Asian pa-

tients with cerebral palsy. Our method of unilateral injection is intended to keep at least 50% of the resting and post-prandial saliva production. This method might theoretically minimize side effects. Our results show significant between-group differences in the Drooling Severity and Frequency Scale and in drooling quotient at most follow-up periods. Interestingly, there were only significant changes at 6 and 12 weeks in saliva weight assessment. The nonsignificant findings are possibly a function of the particular dose used, small sample size, and probably of the marked individual variation. The statistical power was only 69.5% in our study. In the experimental group, the within-subject comparisons were used to eliminate the effect of between-subject variation. Salivary weight was significantly reduced throughout the follow-up period up to 22 weeks postinjection. These differences in saliva weight persisted longer than the other two outcome assessments. BoNT-A injection to contralateral submandibular and parotid glands is a safe and effective
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method for control of drooling in patients with cerebral palsy for at least 12 weeks. Further wellcontrolled studies may provide additional insights into the optimal way to manage drooling in this patient population.
From the Department of Physical Medicine and Rehabilitation (Y.C.L.), E-Da Hospital, Kaohsiung; Department of Physical Therapy (Y.C.L.), I-Shou University, Taiwan; Department of Physical Medicine and Rehabilitation (J.Y.S.), National Taiwan University Hospital, Taipei; Department of Physical Medicine and Rehabilitation (M.L.C.), Show Chwan Memorial Hospital, Changhua; and Department of Physical Medicine and Rehabilitation, China Medical University Hospital School of Medicine (P.Y.Y.), China Medical University, Taiwan. Disclosure: The authors report no conflicts of interest. Received December 4, 2006. Accepted in final form June 1, 2007. Address correspondence and reprint requests to Dr. Pei-Yu Yang, Department of Physical Medicine and Rehabilitation, China Medical University Hospital, 2 Yu-Der Road, Taichung 404, Taiwan, ROC; d7857@www.cmuh.org.tw Copyright 2008 by AAN Enterprises, Inc.

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9.

10. REFERENCES 11. 1. Van De Heyning PH, Marquet JF, Creten WL. Drooling in children with cerebral palsy. Acta Otorhinolaryngol Belg 1980;34:691705. Thomas-Stonell N, Greenberg J. Three treatment approaches and clinical factors in the reduction of drooling. Dysphagia 1988;3:7378. 12.

2.

Webb K, Reddihough DS, Johnson H, Bennett CS, Byrt T. Long-term outcome of saliva-control surgery. Dev Med Child Neurol 1995;37:755762. Jongerius PH, Hoogen FJ, Limbeek J, Gabreels FJ, Hulst K, Rotteveel JJ. Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics 2004;114:620627. Hassin-Baer S, Scheuer E, Buchman AS, Jacobson I, Ben-Zeev B. Botulinum toxin injections for children with excessive drooling. J Child Neurol 2005;20:120123. Suskind DL, Tilton A. Clinical study of Botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy. Laryngoscope 2002;112:7381. Ellies M, Rohrbach-Volland S, Arglebe C, Wilken B, Laskawi R, Hanefeld F.. Successful management of drooling with botulinum toxin A in neurologically disabled children. Neuropediatrics 2002;33:327330. Koheil R, Sochaniwskyj AE, Bablich K, Kenny DJ, Milner M. Biofeedback techniques and behavior modification in the conservative remediation of drooling by children with cerebral palsy. Dev Med Child Neurol 1987;29:1926. Siegel LK, Klingbeil MA. Control of drooling with transdermal scopolamine in a child with cerebral palsy. Dev Med Child Neurol 1991;33:10131014. Camp-Bruno JA, Winsberg BG, Green-Parsons AR, et al. Efficacy of benztropine therapy for drooling. Dev Med Child Neurol 1989;31:30919. Crysdale WS. Management options for the drooling patient. Ear Nose Throat J 1989;68:820830. Greensmith AL, Johnstone BR, Reid SM, Hazard CJ, Johnson SM, Reddihough DS. Prospective analysis of the outcome of surgical management of drooling in the pediatric population: a 10-year experience. Plast Reconstr Surg 2005;116:12331242.

Scott D.Z. Eggers, MD Mark L. Moster, MD Kevin Cranmer, MD

SELECTIVE SACCADIC PALSY AFTER CARDIAC SURGERY

Saccades are rapid eye movements that shift gaze between successive fixation points. We report three patients who awoke from cardiopulmonary bypass with complete persistent loss of all fast eye movements, including voluntary and involuntary saccades and quick phases of nystagmus, with all other eye movements preserved. Case reports. Patient 1. A healthy 50-year-old woman underwent otherwise uncomplicated aortic valve replacement for an incidentally discovered ascending aortic aneurysm. Upon awakening from anesthesia, she noted difficulties directing her gaze and began using head movements to facilitate gaze shifts. She had no dysarthria, dysphagia, or gait instability. She was discharged and had no problems other than her visual symptoms for 3 months when she developed complex partial seizures that responded to levetiracetam.
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Ten months postoperatively, general neurologic examination was notable only for diffuse hyporeflexia. Visual acuity, pupils, visual fields, and funduscopic examination results were normal. Straight-ahead fixation was steady, and no spontaneous saccades, square wave jerks, or nystagmus was seen with ophthalmoscopy. She made no fast volitional or reflexive saccades in any direction, but instead made extremely slow eye movements to eventually reach a target, except for slightly faster downward saccades. Pursuit was smooth and of full range horizontally and vertically, even at high frequencies. With a horizontal optokinetic drum, the eyes became fixed laterally in the orbits without any corrective quick phases, but she made a few downbeats of nystagmus with upward optokinetic drum. Vestibular slow phases, with slow oculocephalics and with rapid head impulse testing, were normal. Torsional head rolling produced excellent ocular counter-rolling, but without any torsional quick phases. Fixation suppression of vestibulo-ocular

BOTULINUM TOXIN TYPE A FOR CONTROL OF DROOLING IN ASIAN PATIENTS WITH CEREBRAL PALSY Yu Ching Lin, Jen Yi Shieh, Mei Li Cheng, et al. Neurology 2008;70;316 DOI 10.1212/01.wnl.0000300421.38081.7d This information is current as of October 28, 2012
Updated Information & Services References Citations including high resolution figures, can be found at: http://www.neurology.org/content/70/4/316.full.html This article cites 12 articles, 2 of which can be accessed free at: http://www.neurology.org/content/70/4/316.full.html#ref-list-1 This article has been cited by 1 HighWire-hosted articles: http://www.neurology.org/content/70/4/316.full.html#related-ur ls Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus

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