e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
Official Journal of the European Paediatric Neurology Society
Review article
Evaluation of the efficacy of cervical perivascular sympathectomy on drooling in children with athetoid cerebral palsy Yu Duan a, Xing Gao b, Xiaoqi Luo b, Chengyan Sun a,b,* a
Department of Cerebral Palsy Center, Sichuan Rehabilitation Hospital, Bayi road, Yongning Town, Wenjiang District, Chengdu, Sichuan, 611135, China b Department of Functional Neurosurgery, Shanghai Tong Ren Hospital, # 1111, Xianxia road, Changning District, Shanghai, 200336, China
article info
abstract
Article history:
Objective: To evaluate the efficacy of cervical perivascular sympathectomy (CPVS) for
Received 29 August 2014
drooling in children with athetoid cerebral palsy (ACP).
Received in revised form
Methods: The severity and frequency of drooling and the amount of salivation of 32 ACP
16 January 2015
children with drooling were evaluated before CPVS and at 4th, 12th and 24 weeks post-
Accepted 18 January 2015
operatively by the teacher drooling scale (TDS) and salivary flow rate (SFR). Results: Fifteen children exhibited improvements on drooling according to the TDS score at
Keywords:
4th week after surgery (P < 0.05). Later, the number of children decreased to 10 at 12th week
Cervical perivascular sym-
(P < 0.05) and to 8 at 24 week after surgery (P < 0.05). SFR was 0.67 mg/min at baseline,
pathectiomy
which decreased to 0.58 mg/min (P < 0.05) at 4th week after surgery. However, SFR showed
Athetoid cerebral palsy
a gradual increase at 12th week and 24 week with no significant difference.
Drooling
Conclusions: Although CPVS was effective in improving drooling in some children with ACP,
Teacher drooling scale
the results were not satisfactory. Thus, CPVS still needs to be cautiously used. Further-
Salivary flow rate
more, more rigorous clinical studies should be performed to detect the effectiveness and safety of this procedure. © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 Subjects and method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.1. Collected subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.2. Drooling evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.3. Hospitalization process and operative procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
* Corresponding author. Department of Functional Neurosurgery, Shanghai Tong Ren Hospital, # 1111, Xianxia road, Changning District, Shanghai, 200336, China. Tel.: þ86 13512135189; fax: þ86 28 21 62908857. E-mail address: [email protected] (C. Sun). http://dx.doi.org/10.1016/j.ejpn.2015.01.007 1090-3798/© 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
3.
4. 5. 6.
1.
281
2.4. Interviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 2.5. Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.1. TDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.2. SFR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.3. Side effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
Introduction
Cerebral palsy (CP) is the commonest neurodisabling disease in childhood with 22%e40% incidence of excessive drooling co-morbidity.1,2 Compared with typically developing children, the patients with drooling do not produce excessive saliva.3 The main factors on drooling may include the serious motor or intellectual impairment, poor head control, active seizure, no useful speech, poor lip closure and dysphagia.1,3e5 “Excessive drooling” may increase the burden of care for parents and carers6 or result in low self-esteem and social isolation in some children.7 There is no definite consensus regarding the interventions that are safe and effective in managing drooling in children with CP. Physical and behavioral therapies can be combined with other treatments, oral medications, botulinum injections and salivary glands surgeries are designed to reduce the amount of saliva secretion. In some studies, these interventions have been reported to exhibit recurrence in some individuals in the long term.8,9 Constipation, urinary retention, vomiting, diarrhea are common complications of oral medications.10 It is noteworthy that BTI do not improve the swallowing function and may even make it worse.11,12 Some surgeries in salivary glands showed effective and stable results in long term follow up,13 however, a large proportion of patients experienced different complications, regrettably, a small part of which were serious and irreversible, such as hemorrhage, swelling, aspiration pneumonia.13,14 In 1970s, neurectomy was introduced in treating excessive drooling. Parasympathetic denervation or tympanic nerve sectioning is initially effective in treating drooling, but the results were disappointing in the long term,15 moreover, serious complications were reported, such as hearing and taste loss.16 Dyskinesia is a major subtype of CP with involuntary movements. If there is increased activity with reduced tone, the children with dyskinetic CP were classified as choreoathetoid or athetoid.17 In a previous study conducted in China, cervical perivascular sympathectomy (CPVS), another neurectomical intervention, was employed to treat children with athetoid cerebral palsy (ACP). After a 1-year follow-up, the parents or caregivers of 40% of the patients were satisfied with the improvement in drooling, furthermore, CPVS was also effective in improving many other symptoms in these children, such as the movements of head and neck, upper limb coordination and speech.18
However, there are few reports on the effect of CPVS in treating children with ACP. Whether CPVS could be a significant drooling choice for the children, it has not been proven by clinical study. The operation was introduced in Sichuan Rehabilitation Hospital, China, in March 2012. In this retrospective cohort study, teacher drooling scale (TDS) and salivary flow rate (SFR) were used to evaluate the frequency and degree of drooling and the amount of salivation in children with ACP before and after the intervention in 24 weeks.
2.
Subjects and method
2.1.
Collected subjects
From March 2012 to December 2013, there were 105 children with ACP who received CPVS in Sichuan Rehabilitation Hospital, China. To retrospectively evaluate the effect of CPVS on drooling, the inclusive criteria of CPVS were as follows: (1) moderate to severe drooling (TDS score 3); (2) parents' or caregivers' total understanding of the potential benefits and risks of the CPVS; (3) had no improvement in the past 6 months with rehabilitation for drooling. The exclusive criteria of the study were as follows: (1) subjects had not received any treatments such as botulinum toxin injection or anticholinergic medications in 6 months before or after CPVS. (2) previous maxillofacial surgery that might interfere in salivary production or flow. (3) moderate or serious intellectual impairment. At last, 32 patients met the inclusive criteria. The clinical data of these 32 children were collected and analyzed in our study. The age of the subjects ranged from 4 to 16 years and their data are listed in Table 1.
2.2.
Drooling evaluation
The frequency and degree of drooling were evaluated according to the Teacher Drooling Scale (TDS), consisting of a 5point scale for severity and frequency (Table 2). A score 5 indicates constantly wet and saliva leaking on clothes and furniture, score 3 means occasionally drooling, and score 1 indicates no drooling.19 1-point decrease was considered improvement in TDS. The scores was evaluated by speech therapist, parents or caregivers together according to average performance of the all daytime. The process of salivary flow rate (SFR) measurement was as follows. The children were assessed in the morning with an
282
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
erect sitting position. Drinking and eating before the assessment were not permitted. The method was based on Jongerius' study20: absorbent cotton rolls were placed at the orifices of the submandibular and parotid glands for 2 min, the procedure was repeated after 30 min. The SFR was calculated by using the following formula: SFR (mg/min) ¼ increase in the weight of the rolls [mg]/time of collection [min]. The measurement was performed in a quiet room avoiding any unnecessary stimulations. All assessments were completed at three days before CPVS (as baseline SFR) and the 4th week, 12th week, 24th week, postoperatively.
2.3.
Hospitalization process and operative procedure
The children would spend ten days in hospital for preoperative tests, assessments and postoperative recovery. Generally, the surgery would be arranged at the fourth day. Six days after the surgery, patients could be discharged. Any food or water were prohibited six h before the surgery, One hour before surgery, 250 ml of 5% glucose was infused. General anesthesia by endotracheal intubation and inhalation was employed. The subjects were placed in supine position with the head thrown back to expose anterior cervical region as much as possible. Along the inner edge of the sternocleidomastoid muscle where the carotid artery exhibited strongest pulsation, a 3-cm longitudinal incision was made. The neck tensor fascia lata was cut and the carotid sheath was exposed, the carotid artery was isolated and the 2-cm carotid adventitia was completely stripped (Fig. 1). The adventitias on right side and left would be both removed and the steps were the same. Six hours after recovery from the general anesthesia, No intravenous fluids were administrated after returning to the ward. The patients could have normal diet the next day.
2.4.
Interviews
Whether there were the improvements in swallow function, speech and movement control, the patients or caregivers would be interviewed at same time points as drooling assessment.
Table 1 e Characteristics of the children with DCP. Characteristic Male/Female Mean age, y (SD) Epilepsy Mobility Walks independently Walks with aids Non-ambulant Communication Speech clearly Speech unclearly Little/no speech Swallow function Little/no dysphagia Dysphagia
Number (32) 17/15 8.3(3.3) 7 19 8 5 2 21 9 3 29
Table 2 e Degrees of the teacher drooling scale. Degree 1 2 3 4 5
2.5.
Description No drooling Infrequent drooling, small amount Occasional drooling, intermittent all day Frequent drooling, but not profuse Constant drooling, always wet
Statistics
Statistical analysis was performed with SPSS software version 22 (SPSS, IBM, Chicago, USA). The nonparametric Wilcoxon signed-rank test was performed to compare the difference in TDS (scale data). A student's t-test was performed to analyze the changes in SFR (continuous data; P < 0.05 was considered as significant).
3.
Results
3.1.
TDS
4 weeks after CPVS, 15 children (46.9%) exhibited improvements in drooling, while the number of effective children decreased to 10 (31.2%) at the 12th week and to 8 (25%) at the 24th week. The results were all of statistical significance at every time points after surgery, p < 0.05 (Fig. 2).
3.2.
SFR
The mean SFR was 0.67 mg/min at baseline. At the 4th week after CPVS, the SFR decreased significantly to 0.58 mg/min (P < 0.05). Over time, the SFR gradually increased to 0.61 mg/ min at the 12th week and 0.64 mg/min at the 24th week, both were not significant (Fig. 3).
3.3.
Side effects
Postoperative pain were found in 5 patients. Swelling of wound was observed through careful digital palpation in one subject after the surgery, then subcutaneous hematoma (maximum of 4 ml) was detected by ultrasonic inspection. The hematoma was gradually absorbed in 3 weeks. One patient (TDS score of 3 before surgery) exhibited aggravated drooling after the CPVS, presenting a TDS score of 4 after surgery at the 12th weeks, and did not improve over time.
4.
Discussion
As a novel treatment for the ACP children with drooling, the results were not satisfied. No more than half of the children got benefit from this invasive method at short term, the number of responsive children even decreased over time. From another point of view, it is undeniable that CPVS could reduce the amount of salivation and improve drooling in some
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
Fig. 1 e Intraoperative photographs of cervical perivascular sympathectomy. A ¼ common carotid artery. B ¼ carotid adventitia.
children, however, the rate was much less than Xu lin's report.18 CPVS was initially used in children with nervous system diseases, it was reported that the surgery could prevent the deterioration of vascular malformation in patients with moyamoya disease.21,22 For the treatments of moyamoya disease at present, the surgery was not the priority, because of its inexact effectiveness.23 Periarterial sympathectomy (PAS) can also reduce sympathetic nerve effect, relieve vascular spasm and increase the blood supply. Combining with postoperative oral medications, the patients with chronic ischemic hands could receive long-term aggravation of symptoms by PAS.24 In lower limbs, PAS of the dorsalis pedis, posterior tibial and anterior tibial arteries also could ameliorate foot symptoms, facilitate healing of toe ulcerations, and reduces the incidence of toe amputations.25 There may be several reasons for improvements of drooling in the ACP children after CPVS. The superior cervical ganglion innervates many targets such as carotid artery and submandibular gland in head, neck and face.26,27 The protein secretion in saliva is evoked by the importance of sympathetic impulses according to the experiments in which electrical stimulation of the sympathetic nerve supplies to the parotid28 or submandibular glands.28 As the postganglionic fibers being resected, some postganglionic neurons could be injured and the ganglionic sympathetic impulses would be weaken, so the SFR decreased at 4 weeks. However, the SFR increased later, it may indicate the injured postganglionic axons innervated salivary glands or other targets again.27 In cat model, the blood flow increased in carotid blood artery with significant difference and decreased in salivary glands following the cervical sympathectomy. The flow could
283
reverse with the stimulation of the cervical sympathetic nerve.29 Due to the mechanism of cerebral autoregulation, the blood circulation may not change significantly after sympathectomy in brain.30 While, the decrease of the blood flow in salivary glands may impair the function of saliva secretion in short term. The patients with chronic ischemia of lower limbs could get benefits in perfusion of femoral and calf muscles and increase the maximal blood flow rate in the popliteal artery from lumbar sympethetomy.31 Currently, perivascular sympathectomy or sympathectomy is performed in treating ulcer, pain, refractory hypertension or many other diseases. It has been demonstrated the surgery could diminish sympathetic nerve effect, relieve vascular spasm, which might be another mechanism for drooling. It is well known that improved head control and swallowing abilities are key factors affecting drooling.1,32 In this study, those relative symptom improved in some different children, such as swallow function, speech or head and posture control, according to the interview of their parents or caregiver. These improvements may be helpful for drooling control. In addition, the effect of CPVS in improving the neural function has also been reported. The trigeminal ganglion which is the sensory afferent pathway of swallow function, showed an increase in nerve growth factor after sympathectomy.33 Due to increasing neurotrophic factors, the brain function or neuromodulation may be nourished, subsequently. In the present study, only three patients presented a more than 1-point decrease in TDS score after 24 weeks follow up. All of these patients exhibited the following characteristics: (1) age of 4e6 years; (2) showed no or little swallow function impaired; (3) underwent systematic swallowing function training after surgery. On the contrary, the children with poor intelligence and worse oral function demonstrated limited response; those who with most serious drooling at a score 5 in TDS showed no response from the surgery. These findings indicated that those who are younger with moderate drooling, better neural plasticity may get more benefits from the
Fig. 2 e The change of teacher drooling scale before and after the surgery. * Nonparametric Wilcoxon single test, P < 0.05.
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e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
Fig. 3 e The change of salivary flow rate before and after the surgery. * A student's t-test, P < 0.05.
surgery and postoperative training is of great importance to keep positive results in long term.
5.
Conclusion
Although CPVS was effective in improving drooling in some children with ACP, the results were not satisfactory. Thus, CPVS still needs to be cautiously used. Furthermore, more rigorous clinical studies should be performed to detect the effectiveness and safety of this procedure.
Conflict of interest statement The authors declare that they have no competing financial interests and personal relationships with other people or organizations that can inappropriately influence our work.
references
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5. Rogers B, Arvedson J. Assessment of infant oral sensorimotor and swallowing function. Ment Retard Dev Disabil Res Rev 2005;11:74e82. 6. Erasmus CE, van Hulst K, Rotteveel JJ, Willemsen MA, Jongerius PH. Clinical practice: swallowing problems in cerebral palsy. Eur J Pediatr 2012;171:409e14. 7. van der Burg JJ, Jongerius PH, van Limbeek J, van Hulst K, Rotteveel JJ. Social interaction and self-esteem of children with cerebral palsy after treatment for severe drooling. Eur J Pediatr 2006;165:37e41. 8. Ellies M, Gottstein U, Rohrbach-Volland S, Arglebe C, Laskawi R. Reduction of salivary flow with botulinum toxin: extended report on 33 patients with drooling, salivary fistulas, and sialadenitis. Laryngoscope 2004;114:1856e60. 9. Martin TJ, Conley SF. Long-term efficacy of intra-oral surgery for sialorrhea. Otolaryngol Head Neck Surg Off J Am Acad Otolaryngol Head Neck Surg 2007;137:54e8. 10. Mier RJ, Bachrach SJ, Lakin RC, Barker T, Childs J, Moran M. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000;154:1214e8. 11. Basciani M, Di Rienzo F, Fontana A, Copetti M, Pellegrini F, Intiso D. Botulinum toxin type B for sialorrhoea in children with cerebral palsy: a randomized trial comparing three doses. Dev Med Child Neurol 2011;53:559e64. 12. Chan KH, Liang C, Wilson P, Higgins D, Allen GC. Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea. JAMA Otolaryngol Head Neck Surg 2013;139:134e8. 13. Greensmith AL, Johnstone BR, Reid SM, Hazard CJ, Johnson HM, Reddihough DS. Prospective analysis of the outcome of surgical management of drooling in the pediatric population: a 10-year experience. Plast Reconstr Surg 2005;116:1233e42. 14. Glynn F, O'Dwyer TP. Does the addition of sublingual gland excision to submandibular duct relocation give better overall results in drooling control? Clin Otolaryngol Off J Ent UK Off J Neth Soc Oto Rhino Laryngol Cervico Facial Surg 2007;32:103e7. 15. Parisier SC, Blitzer A, Binder WJ, Friedman WF, Marovitz WF. Tympanic neurectomy and chorda tympanectomy for the control of drooling. Arch Otolaryngol 1978;104:273e7. 16. Wilkie TF. On the bad effects of nerve sections for the control of drooling. Plast Reconstr Surg 1977;60:439e40. 17. Shankaran S. Prevention, diagnosis, and treatment of cerebral palsy in near-term and term infants. Clin Obstet Gynecol 2008;51:829e39. 18. Xu SG, Xu L, Cao X, Jiao Y. Cervical perivascular sympathectomy for the treatment of athetoid cerebral palsy. Zhongguo Gu Shang China J Orthop Traumatol 2010;23:291e3. 19. Jongerius PH, van Hulst K, van den Hoogen FJ, Rotteveel JJ. The treatment of posterior drooling by botulinum toxin in a child with cerebral palsy. J Pediatr Gastroenterol Nutr 2005;41:351e3. 20. Jongerius PH, van den Hoogen FJ, van Limbeek J, Gabreels FJ, van Hulst K, Rotteveel JJ. Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics 2004;114:620e7. 21. Liu XJ, Zhang D, Wang S, Zhao YL, Teo M, Wang R, et al. Clinical features and long-term outcomes of moyamoya disease: a single-center experience with 528 cases in China. J Neurosurg 2014:1e8. 22. Suzuki J, Takaku A, Kodama N, Sato S. An attempt to treat cerebrovascular ‘Moyamoya’disease in children. Pediatr Neurosurg 1975;1:193e206. 23. Kuroda S, Houkin K. Bypass surgery for moyamoya disease: concept and essence of sugical techniques. Neurol Med Chir 2012;52:287e94.
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24. Murata K, Omokawa S, Kobata Y, Tanaka Y, Yajima H, Tamai S. Long-term follow-up of periarterial sympathectomy for chronic digital ischaemia. J Hand Surg Eur Vol 2012;37:788e93. 25. Li Z, Smith BP, Holden M, Koman LA. Periarterial sympathectomy of the foot for the treatment of necrotizing Raynaud's phenomena. J Reconstr Microsurg 2009;25:133e7. 26. Proctor GB, Carpenter GH. Regulation of salivary gland function by autonomic nerves. Aut Neurosci Basic Clin 2007;133:3e18. 27. Hesp ZC, Zhu Z, Morris TA, Walker RG, Isaacson LG. Sympathetic reinnervation of peripheral targets following bilateral axotomy of the adult superior cervical ganglion. Brain Res 2012;1473:44e54. 28. Asking B, Gjorstrup P. Synthesis and secretion of amylase in the rat parotid gland following autonomic nerve stimulation in vivo. Acta Physiol Scand 1987;130:439e45.
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29. Spierings EL. Headache following cervical sympathectomy and results of a blood flow study in the cat. Headache 2003;43:410e4. 30. Spierings EL. Acute and chronic hypertensive headache and hypertensive encephalopathy. Cephalalgia Int J Headache 2002;22:313e6. 31. Dabrowski J, Mikosinski J, Kusmierek J. Scintigraphic and ultrasonographic assessment of the effect of lumbar sympathectomy upon chronic arteriosclerotic ischaemia of lower extremities. Nucl Med Rev Central East Eur 2003;6:17e22. 32. Waterman ET, Koltai PJ, Downey JC, Cacace AT. Swallowing disorders in a population of children with cerebral palsy. Int J Pediatr Otorhinolaryngol 1992;24:63e71. 33. Randolph CL, Bierl MA, Isaacson LG. Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input. Brain Res 2007;1144:59e69.
Official Journal of the European Paediatric Neurology Society
Review article
Evaluation of the efficacy of cervical perivascular sympathectomy on drooling in children with athetoid cerebral palsy Yu Duan a, Xing Gao b, Xiaoqi Luo b, Chengyan Sun a,b,* a
Department of Cerebral Palsy Center, Sichuan Rehabilitation Hospital, Bayi road, Yongning Town, Wenjiang District, Chengdu, Sichuan, 611135, China b Department of Functional Neurosurgery, Shanghai Tong Ren Hospital, # 1111, Xianxia road, Changning District, Shanghai, 200336, China
article info
abstract
Article history:
Objective: To evaluate the efficacy of cervical perivascular sympathectomy (CPVS) for
Received 29 August 2014
drooling in children with athetoid cerebral palsy (ACP).
Received in revised form
Methods: The severity and frequency of drooling and the amount of salivation of 32 ACP
16 January 2015
children with drooling were evaluated before CPVS and at 4th, 12th and 24 weeks post-
Accepted 18 January 2015
operatively by the teacher drooling scale (TDS) and salivary flow rate (SFR). Results: Fifteen children exhibited improvements on drooling according to the TDS score at
Keywords:
4th week after surgery (P < 0.05). Later, the number of children decreased to 10 at 12th week
Cervical perivascular sym-
(P < 0.05) and to 8 at 24 week after surgery (P < 0.05). SFR was 0.67 mg/min at baseline,
pathectiomy
which decreased to 0.58 mg/min (P < 0.05) at 4th week after surgery. However, SFR showed
Athetoid cerebral palsy
a gradual increase at 12th week and 24 week with no significant difference.
Drooling
Conclusions: Although CPVS was effective in improving drooling in some children with ACP,
Teacher drooling scale
the results were not satisfactory. Thus, CPVS still needs to be cautiously used. Further-
Salivary flow rate
more, more rigorous clinical studies should be performed to detect the effectiveness and safety of this procedure. © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 Subjects and method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.1. Collected subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.2. Drooling evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2.3. Hospitalization process and operative procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
* Corresponding author. Department of Functional Neurosurgery, Shanghai Tong Ren Hospital, # 1111, Xianxia road, Changning District, Shanghai, 200336, China. Tel.: þ86 13512135189; fax: þ86 28 21 62908857. E-mail address: [email protected] (C. Sun). http://dx.doi.org/10.1016/j.ejpn.2015.01.007 1090-3798/© 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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3.
4. 5. 6.
1.
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2.4. Interviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 2.5. Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.1. TDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.2. SFR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3.3. Side effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
Introduction
Cerebral palsy (CP) is the commonest neurodisabling disease in childhood with 22%e40% incidence of excessive drooling co-morbidity.1,2 Compared with typically developing children, the patients with drooling do not produce excessive saliva.3 The main factors on drooling may include the serious motor or intellectual impairment, poor head control, active seizure, no useful speech, poor lip closure and dysphagia.1,3e5 “Excessive drooling” may increase the burden of care for parents and carers6 or result in low self-esteem and social isolation in some children.7 There is no definite consensus regarding the interventions that are safe and effective in managing drooling in children with CP. Physical and behavioral therapies can be combined with other treatments, oral medications, botulinum injections and salivary glands surgeries are designed to reduce the amount of saliva secretion. In some studies, these interventions have been reported to exhibit recurrence in some individuals in the long term.8,9 Constipation, urinary retention, vomiting, diarrhea are common complications of oral medications.10 It is noteworthy that BTI do not improve the swallowing function and may even make it worse.11,12 Some surgeries in salivary glands showed effective and stable results in long term follow up,13 however, a large proportion of patients experienced different complications, regrettably, a small part of which were serious and irreversible, such as hemorrhage, swelling, aspiration pneumonia.13,14 In 1970s, neurectomy was introduced in treating excessive drooling. Parasympathetic denervation or tympanic nerve sectioning is initially effective in treating drooling, but the results were disappointing in the long term,15 moreover, serious complications were reported, such as hearing and taste loss.16 Dyskinesia is a major subtype of CP with involuntary movements. If there is increased activity with reduced tone, the children with dyskinetic CP were classified as choreoathetoid or athetoid.17 In a previous study conducted in China, cervical perivascular sympathectomy (CPVS), another neurectomical intervention, was employed to treat children with athetoid cerebral palsy (ACP). After a 1-year follow-up, the parents or caregivers of 40% of the patients were satisfied with the improvement in drooling, furthermore, CPVS was also effective in improving many other symptoms in these children, such as the movements of head and neck, upper limb coordination and speech.18
However, there are few reports on the effect of CPVS in treating children with ACP. Whether CPVS could be a significant drooling choice for the children, it has not been proven by clinical study. The operation was introduced in Sichuan Rehabilitation Hospital, China, in March 2012. In this retrospective cohort study, teacher drooling scale (TDS) and salivary flow rate (SFR) were used to evaluate the frequency and degree of drooling and the amount of salivation in children with ACP before and after the intervention in 24 weeks.
2.
Subjects and method
2.1.
Collected subjects
From March 2012 to December 2013, there were 105 children with ACP who received CPVS in Sichuan Rehabilitation Hospital, China. To retrospectively evaluate the effect of CPVS on drooling, the inclusive criteria of CPVS were as follows: (1) moderate to severe drooling (TDS score 3); (2) parents' or caregivers' total understanding of the potential benefits and risks of the CPVS; (3) had no improvement in the past 6 months with rehabilitation for drooling. The exclusive criteria of the study were as follows: (1) subjects had not received any treatments such as botulinum toxin injection or anticholinergic medications in 6 months before or after CPVS. (2) previous maxillofacial surgery that might interfere in salivary production or flow. (3) moderate or serious intellectual impairment. At last, 32 patients met the inclusive criteria. The clinical data of these 32 children were collected and analyzed in our study. The age of the subjects ranged from 4 to 16 years and their data are listed in Table 1.
2.2.
Drooling evaluation
The frequency and degree of drooling were evaluated according to the Teacher Drooling Scale (TDS), consisting of a 5point scale for severity and frequency (Table 2). A score 5 indicates constantly wet and saliva leaking on clothes and furniture, score 3 means occasionally drooling, and score 1 indicates no drooling.19 1-point decrease was considered improvement in TDS. The scores was evaluated by speech therapist, parents or caregivers together according to average performance of the all daytime. The process of salivary flow rate (SFR) measurement was as follows. The children were assessed in the morning with an
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erect sitting position. Drinking and eating before the assessment were not permitted. The method was based on Jongerius' study20: absorbent cotton rolls were placed at the orifices of the submandibular and parotid glands for 2 min, the procedure was repeated after 30 min. The SFR was calculated by using the following formula: SFR (mg/min) ¼ increase in the weight of the rolls [mg]/time of collection [min]. The measurement was performed in a quiet room avoiding any unnecessary stimulations. All assessments were completed at three days before CPVS (as baseline SFR) and the 4th week, 12th week, 24th week, postoperatively.
2.3.
Hospitalization process and operative procedure
The children would spend ten days in hospital for preoperative tests, assessments and postoperative recovery. Generally, the surgery would be arranged at the fourth day. Six days after the surgery, patients could be discharged. Any food or water were prohibited six h before the surgery, One hour before surgery, 250 ml of 5% glucose was infused. General anesthesia by endotracheal intubation and inhalation was employed. The subjects were placed in supine position with the head thrown back to expose anterior cervical region as much as possible. Along the inner edge of the sternocleidomastoid muscle where the carotid artery exhibited strongest pulsation, a 3-cm longitudinal incision was made. The neck tensor fascia lata was cut and the carotid sheath was exposed, the carotid artery was isolated and the 2-cm carotid adventitia was completely stripped (Fig. 1). The adventitias on right side and left would be both removed and the steps were the same. Six hours after recovery from the general anesthesia, No intravenous fluids were administrated after returning to the ward. The patients could have normal diet the next day.
2.4.
Interviews
Whether there were the improvements in swallow function, speech and movement control, the patients or caregivers would be interviewed at same time points as drooling assessment.
Table 1 e Characteristics of the children with DCP. Characteristic Male/Female Mean age, y (SD) Epilepsy Mobility Walks independently Walks with aids Non-ambulant Communication Speech clearly Speech unclearly Little/no speech Swallow function Little/no dysphagia Dysphagia
Number (32) 17/15 8.3(3.3) 7 19 8 5 2 21 9 3 29
Table 2 e Degrees of the teacher drooling scale. Degree 1 2 3 4 5
2.5.
Description No drooling Infrequent drooling, small amount Occasional drooling, intermittent all day Frequent drooling, but not profuse Constant drooling, always wet
Statistics
Statistical analysis was performed with SPSS software version 22 (SPSS, IBM, Chicago, USA). The nonparametric Wilcoxon signed-rank test was performed to compare the difference in TDS (scale data). A student's t-test was performed to analyze the changes in SFR (continuous data; P < 0.05 was considered as significant).
3.
Results
3.1.
TDS
4 weeks after CPVS, 15 children (46.9%) exhibited improvements in drooling, while the number of effective children decreased to 10 (31.2%) at the 12th week and to 8 (25%) at the 24th week. The results were all of statistical significance at every time points after surgery, p < 0.05 (Fig. 2).
3.2.
SFR
The mean SFR was 0.67 mg/min at baseline. At the 4th week after CPVS, the SFR decreased significantly to 0.58 mg/min (P < 0.05). Over time, the SFR gradually increased to 0.61 mg/ min at the 12th week and 0.64 mg/min at the 24th week, both were not significant (Fig. 3).
3.3.
Side effects
Postoperative pain were found in 5 patients. Swelling of wound was observed through careful digital palpation in one subject after the surgery, then subcutaneous hematoma (maximum of 4 ml) was detected by ultrasonic inspection. The hematoma was gradually absorbed in 3 weeks. One patient (TDS score of 3 before surgery) exhibited aggravated drooling after the CPVS, presenting a TDS score of 4 after surgery at the 12th weeks, and did not improve over time.
4.
Discussion
As a novel treatment for the ACP children with drooling, the results were not satisfied. No more than half of the children got benefit from this invasive method at short term, the number of responsive children even decreased over time. From another point of view, it is undeniable that CPVS could reduce the amount of salivation and improve drooling in some
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
Fig. 1 e Intraoperative photographs of cervical perivascular sympathectomy. A ¼ common carotid artery. B ¼ carotid adventitia.
children, however, the rate was much less than Xu lin's report.18 CPVS was initially used in children with nervous system diseases, it was reported that the surgery could prevent the deterioration of vascular malformation in patients with moyamoya disease.21,22 For the treatments of moyamoya disease at present, the surgery was not the priority, because of its inexact effectiveness.23 Periarterial sympathectomy (PAS) can also reduce sympathetic nerve effect, relieve vascular spasm and increase the blood supply. Combining with postoperative oral medications, the patients with chronic ischemic hands could receive long-term aggravation of symptoms by PAS.24 In lower limbs, PAS of the dorsalis pedis, posterior tibial and anterior tibial arteries also could ameliorate foot symptoms, facilitate healing of toe ulcerations, and reduces the incidence of toe amputations.25 There may be several reasons for improvements of drooling in the ACP children after CPVS. The superior cervical ganglion innervates many targets such as carotid artery and submandibular gland in head, neck and face.26,27 The protein secretion in saliva is evoked by the importance of sympathetic impulses according to the experiments in which electrical stimulation of the sympathetic nerve supplies to the parotid28 or submandibular glands.28 As the postganglionic fibers being resected, some postganglionic neurons could be injured and the ganglionic sympathetic impulses would be weaken, so the SFR decreased at 4 weeks. However, the SFR increased later, it may indicate the injured postganglionic axons innervated salivary glands or other targets again.27 In cat model, the blood flow increased in carotid blood artery with significant difference and decreased in salivary glands following the cervical sympathectomy. The flow could
283
reverse with the stimulation of the cervical sympathetic nerve.29 Due to the mechanism of cerebral autoregulation, the blood circulation may not change significantly after sympathectomy in brain.30 While, the decrease of the blood flow in salivary glands may impair the function of saliva secretion in short term. The patients with chronic ischemia of lower limbs could get benefits in perfusion of femoral and calf muscles and increase the maximal blood flow rate in the popliteal artery from lumbar sympethetomy.31 Currently, perivascular sympathectomy or sympathectomy is performed in treating ulcer, pain, refractory hypertension or many other diseases. It has been demonstrated the surgery could diminish sympathetic nerve effect, relieve vascular spasm, which might be another mechanism for drooling. It is well known that improved head control and swallowing abilities are key factors affecting drooling.1,32 In this study, those relative symptom improved in some different children, such as swallow function, speech or head and posture control, according to the interview of their parents or caregiver. These improvements may be helpful for drooling control. In addition, the effect of CPVS in improving the neural function has also been reported. The trigeminal ganglion which is the sensory afferent pathway of swallow function, showed an increase in nerve growth factor after sympathectomy.33 Due to increasing neurotrophic factors, the brain function or neuromodulation may be nourished, subsequently. In the present study, only three patients presented a more than 1-point decrease in TDS score after 24 weeks follow up. All of these patients exhibited the following characteristics: (1) age of 4e6 years; (2) showed no or little swallow function impaired; (3) underwent systematic swallowing function training after surgery. On the contrary, the children with poor intelligence and worse oral function demonstrated limited response; those who with most serious drooling at a score 5 in TDS showed no response from the surgery. These findings indicated that those who are younger with moderate drooling, better neural plasticity may get more benefits from the
Fig. 2 e The change of teacher drooling scale before and after the surgery. * Nonparametric Wilcoxon single test, P < 0.05.
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e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 9 ( 2 0 1 5 ) 2 8 0 e2 8 5
Fig. 3 e The change of salivary flow rate before and after the surgery. * A student's t-test, P < 0.05.
surgery and postoperative training is of great importance to keep positive results in long term.
5.
Conclusion
Although CPVS was effective in improving drooling in some children with ACP, the results were not satisfactory. Thus, CPVS still needs to be cautiously used. Furthermore, more rigorous clinical studies should be performed to detect the effectiveness and safety of this procedure.
Conflict of interest statement The authors declare that they have no competing financial interests and personal relationships with other people or organizations that can inappropriately influence our work.
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