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Early laparoscopic fundoplication and gastrostomy in infants with spinal muscular atrophy type I
Journal of Pediatric Surgery (2008) 43, 2031–2037
www.elsevier.com/locate/jpedsurg
Early laparoscopic fundoplication and gastrostomy in infants with spinal muscular atrophy type I Emily T. Durkin a , Mary K. Schroth b , Margaret Helin a , Aimen F. Shaaban c,⁎ a
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375, USA Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA c Department of Surgery, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA b
Received 24 January 2008; revised 5 May 2008; accepted 21 May 2008
Key words: Neuromuscular disorders; Nutrition; Aspiration; Morbidity/Mortality; Enteral feeding
Abstract Background/Purpose: Spinal muscular atrophy (SMA) in children leads to progressive muscle weakness, dysphagia, aspiration, and death. We hypothesized that early laparoscopic fundoplication and gastrostomy in infants with SMA type I could be performed safely perhaps leading to fewer aspiration events and improved nutritional status. Methods: Children diagnosed with SMA type I from 2002 through 2005 were included (n = 12). All children underwent laparoscopic Nissen fundoplication with gastrostomy shortly after diagnosis. Postoperative respiratory management and discharge criteria were standardized. Results: All patients were extubated immediately postoperatively. There were no significant complications. Average time to full feeding and inpatient length of stay were 42 ± 4.9 hours (range, 30-48 hours) and 78 ± 22.5 hours (range, 44-120 hours), respectively. Mean weight-for-length percentile was doubled at 1 year postoperatively (P = .03). The number of respiratory-related hospitalizations in the cohort decreased by almost 50% in the ensuing 12 months after surgery, although this did not reach statistical significance in this small cohort (P = .34). Conclusions: Early laparoscopic fundoplication and gastrostomy is safe and is associated with improved nutritional status. A trend toward fewer significant long-term aspiration-related events was seen after fundoplication. To better assess the long-term benefits of performing an antireflux procedure in these high-risk patients, a larger prospective trial comparing current nutritional support practices is needed. © 2008 Elsevier Inc. All rights reserved.
Spinal muscular atrophy (SMA) is an autosomal recessive neurological disease that affects 1 in 6000 to 10,000 children and is caused by degeneration of the anterior horn cells in the spinal cord [1]. The most common and severe form of SMA is designated as type I, also known as Werdnig-Hoffman Disease or Floppy Baby syndrome. Children affected with ⁎ Corresponding author. Tel.: +1 608 263 9419; fax: +1 608 263 7652. E-mail address: [email protected] (A.F. Shaaban). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.05.035
SMA type I typically display the most severe neurological findings with generalized weakness appearing within the first 3 months of life. Bulbar dysfunction is universal in these patients and typically leads to feeding and swallowing difficulties, which result in aspiration pneumonia and eventual death [2]. Ninety-eight percent of children with SMA have homozygous deletion of the survival motor neuron 1 (SMN1) gene located on chromosome 5q13 [3]. The diagnosis of SMA is
2032 typically made in conjunction with physical examination findings and genetic testing for SMN gene deletion or mutation [4,5]. Traditionally, SMA has been designated into 3 types based upon the age of onset: type I is associated with symptom onset before age 6 months; type II is associated with symptom onset after age 6 months and before 18 months; and type III is associated with symptom onset after age of 18 months [2]. Recently, the International SMA Consortium significantly revised this classification system and reclassified affected individuals based on age at onset of symptoms, highest motor function achieved, and age of death [6]. The natural history of SMA type I is such that 80% of children will die within the first year of life [7]. However, in centers that routinely care for children with complex neuromuscular disorders (NMDs), the life expectancy for children with SMA type I has been extended from less than 1 year to more than 2 years of age [8]. Advances in airwayclearance, noninvasive ventilatory support and nutritional supplementation have likely led to this improved survival. In addition, systematic integration of pediatric subspecialty management, as recommended by the International SMA Consortium, greatly enhances the care of these patients [6]. Nutritional support for patients with SMA type I remains a clinical challenge without a clear consensus in the available literature. Children with SMA type I in particular tire early during feedings and quickly become unable to achieve adequate caloric intake to prevent weight loss resulting in worsening muscle atrophy. As the disease progresses, bulbar dysfunction, respiratory muscle fatigue, and malnutrition lead to aspiration events and recurrent respiratory tract infections, each of which can potentially become a lifethreatening pneumonia [9]. Although elimination of oral nutritional intake decreases the possibility of oropharyngeal aspiration, gastroesophageal reflux (GER) can still occur in these children. The true incidence of clinically significant GER in patients with SMA type I is unknown; however, it has been reported to be as high as 100% in some series [4,5]. Several studies have evaluated gastrostomy feeding without a concomitant antireflux procedure in patients with SMA in the setting of medically treated GER and have reported high rates of postoperative aspiration pneumonia and death [10,11]. A review of these reports suggest that patients with SMA type I are poor candidates for antireflux operations because of their high perioperative risk, overall poor prognosis, and short life expectancy. Presently, there is little information available in the literature to contradict this conclusion. Only 1 study to date has evaluated the outcome of patients with SMA undergoing antireflux procedures [12]. Unfortunately, this study did not evaluate type I patients, specifically those who are theoretically subject to the highest perioperative risks. Furthermore, the timing of surgical intervention was not specifically evaluated with regard to prevention of GER in SMA patients. The goal of the current study was to assess the risks and benefits of early referral for an antireflux
E.T. Durkin et al. procedure shortly after diagnosis in children with SMA type I. We hypothesized that a minimally invasive procedure coupled with an aggressive postoperative extubation and airway clearance strategy could be accomplished safely, improve patients' nutritional status, and perhaps reduce future aspiration events.
1. Methods 1.1. Subjects After receiving institutional review board approval, we reviewed the records of children diagnosed with SMA type I at our institution from 2003 to 2005. All patients newly diagnosed with SMA type I during this time were referred for surgical evaluation. At the time of surgical consultation, patients were clinically evaluated for GER by obtaining a detailed history about reflux-related events such as colicky pain episodes, irritability, frequent spitting up, poor sleep habits, frequent waking, and vomiting more than 1 hour after feeds. Patients were evaluated radiographically for the presence of aspiration by a video swallowing study performed by trained pediatric speech pathology personnel. A preoperative barium upper gastrointestinal (UGI) series was obtained to ensure normal gastric anatomy and intestinal rotation before operative intervention. The number of, and precipitating factors for, all preoperative hospitalizations were noted. Patients' baseline length and weight were recorded at all preoperative visits and at the time of surgery.
1.2. Surgical procedure All patients underwent laparoscopic fundoplication and gastrostomy by the same experienced laparoscopic surgeon using an identical technique. An opiate-free general anesthetic was administered, and all patients received a “single-shot” caudal epidural. A 5-trocar method was used. The short gastric vessels were divided, and a hiatal repair was performed in all cases. An esophageal bougie was used to gauge the caliber of the 360° fundoplication, which was 2.5 cm in length. No procedures were converted to an open technique. After fundoplication, a percutaneous gastrostomy was created, and a gastrostomy button catheter placed primarily. All patients were extubated immediately postoperatively. Given the high risk of significant postanesthesia atelectasis, patients were observed for 24 hours after surgery in the pediatric intensive care unit with continuous cardiopulmonary monitoring.
1.3. Postoperative respiratory care and feeding After the procedure, patients were extubated to highspan inspiratory-expiratory positive airway pressure (IPAPEPAP) ≥10 bilevel positive airway pressure (BiPAP) per
Early laparoscopic fundoplication and gastrostomy in infants nasal mask ventilation and received every 4 hours airway clearance with chest physiotherapy. This was followed by mechanical insufflation-exsufflation, postural drainage, and mechanical insufflation-exsufflation again. Postoperative pain management consisted of scheduled acetaminophen and intravenous ketorolac for 48 hours. Narcotics were administered as needed for pain control. Patients were jointly managed by the surgical and pulmonary services during their hospitalization. All children were initiated on enteral feeding via gastrostomy at 24 hours postoperatively. Nutritional requirements were calculated to provide 100% of each subject's daily caloric requirement. Half of this requirement was administered during the day in the form of bolus feeds every 3 hours fed by gravity with continuous venting of the gastrostomy to an open syringe. The remainder was administered continuously over 10 hours at night via infusion pump also with continuous venting of the gastrostomy. Patients were initiated at 50% of their total daily requirements and advanced to goal requirements by the second postoperative day. During enteral feeding advancement, all subjects were observed closely for signs of feeding intolerance such as bloating, retching, or abdominal pain. Gastrostomy tubes were continuously vented for the first 2 weeks postoperatively, then progressively clamped until only vented pre- and postfeeding for 30 minutes and while on BiPAP support. Venting of the gastrostomy tubes postfundoplication was done to reduce gastric bloating resulting from the BIPAP treatments that all children received. Patients were discharged from the hospital when they tolerated goal gastrostomy feedings with regular bowel movements and had returned to their preoperative regimen of BiPAP use.
2033 hospitalizations were compared pre- and postoperatively using a 2-tailed Student t test assuming unequal variables. P values ≤.05 were considered significant.
2. Results 2.1. Subjects A total of 15 children were diagnosed with SMA of any type, all confirmed by genetic analysis, between January 2002 and December 2005 at our institution. Surgical referral was made immediately at the time of diagnosis in most cases to study the effect of early intervention for the prevention of GER. Therefore, for the purposes of inclusion in this study, children were classified as having SMA type I if the onset of symptoms began before 6 months of age rather than by the highest motor function achieved. Twelve children met this criterion and were ultimately included in the analysis. Table 1 summarizes the demographics of the study cohort. The average age at diagnosis was 6.2 months (range, 1-9 months), and all children included had symptoms present before diagnosis consistent with the most severe SMA phenotype. An attempt was made in all cases to intervene surgically as soon as possible after the diagnosis of SMA type I was established. Although early surgical referral was made in all cases, preoperative delays were occasionally encountered because of recovery from acute respiratory illness, transfer from outside institutions, and parental scheduling limitations. Ultimately, patients underwent surgery at an average age of 10.1 months (range, 5-14 months).
2.2. Surgical procedure and perioperative results 1.4. Complications and follow-up care Complications were defined as short-term if they occurred less than 30 days following operation and included reintubation for any reason after surgery, significant intraoperative or postoperative bleeding, clinically documented infection, oxygen requirement greater than 24 hours after surgery, prolonged ileus, and clinically or radiographically documented pneumonia. Long-term complications were defined as any complication that occurred more than 30 days postoperatively as a consequence of surgical intervention. Clinical GER symptoms were assessed routinely at all postoperative visits. A baseline UGI was obtained at 6 weeks postoperatively. Growth parameter measurements were obtained at all subsequent clinic visits.
1.5. Statistical methods Averages and ranges were calculated for all categorical variables. Body measurement parameters and number of
All children underwent laparoscopic Nissen fundoplication and feeding gastrostomy placement under general anesthesia in an identical manner performed by the same Table 1
Patient demographics
Patient
Sex
Age at diagnosis (mo)
Age at operation (mo)
1 2 3 4 5 6 7 8 9 10 11 12 Mean ± SD
Male Male Male Female Female Female Male Male Female Female Male Female 50% male
4 4 9 6 1 8 6 6 8 8 9 6 6.2 ± 2.4
11 7 14 12 5 14 9 8 10 12 13 8 10.1 ± 2.9
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E.T. Durkin et al.
Table 2
Perioperative outcomes
Patient
Operative time (min)
Narcotic doses required
Oxygen saturation 4 h (%)
Oxygen saturation 24 h (%)
Time to initiation of feeds (h)
Time to full feeds (h)
Time to first BM (h)
LOS (h)
Complication
1 2 3 4 5 6 7 8 9 10 11 12 Mean
195 135 165 150 173 155 161 193 144 274 161 206 176 ± 38
0 0 1 0 0 0 0 0 0 0 1 0 b1 dose
100 97 100 99 99 96 97 95 99 96 100 97 98 ± 1.8
100 100 99 94 99 95 98 99 97 100 100 95 98 ± 2.2
24 21 22 24 24 22 22 26 21 24 23 20 23 ± 1.7
45 45 41 44 42 46 30 42 45 48 45 35 42 ± 5.1
45 28 42 47 41 48 54 24 34 28 28 45 39 ± 9.8
48 70 44 96 120 60 79 75 74 72 106 74 77 ± 22
– – – – L lung atalectasis – – – – – – – b1
BM indicates bowel movement; LOS, length of stay.
surgeon. Table 2 outlines the perioperative outcome measurements for each patient. Mean operative time was 176 ± 38.6 minutes. All children were extubated immediately postoperatively and transitioned to BiPAP support in the operating room. No patient required reintubation for any reason. The mean oxygen saturation at 4, 12, and 24 hours postoperatively was 98% at each time-point for all children. No child required supplemental oxygen longer than 24 hours. Opioid analgesia in the form of intravenous morphine sulfate was required by only 2 of the children, who each received 1 dose. The average time to full feeds was 42 ± 5.1 hours (range, 30-48), and the average time to first bowel movement was 39 ± 9.8 hours (range, 24-54). One patient was noted to have significant left lung atelectasis on the first postoperative evening, which was diagnosed when a routine postoperative chest x-ray was performed. This patient was managed conservatively with airway clearance measures, identical to those outlined in the Methods section, and a second chest x-ray performed 12 hours later showed complete resolution of the atelectasis. No long-term complications were identified in any of the subjects during the period evaluated. The average length of stay was 77 ± 22 hours (range, 44120). The median length of follow-up was 10.3 ± 7.8 months (range, 1-22 months), and the mean age of the children at that time was 20.8 months (n = 11). The current mean age of the children is 28 months. One child in the series has since died from progressive respiratory failure, unrelated to aspiration, as a result of her disease.
2.3. Aspiration and GER symptom assessment Previous reports have documented a high rate of swallowing disorders in patients with SMA; therefore, this was routinely assessed clinically at the time of surgical
referral [9]. All of the children who underwent video swallow study (9/9) displayed abnormal findings ranging from delayed swallowing to severe oropharyngeal aspiration. Clinical evidence of GER was established preoperatively by history in 8 (66%) of 12 patients. Patient 10 had a previous percutaneous endoscopic gastrostomy without a concomitant fundoplication. This patient's GER symptoms dramatically worsened after initiating gastrostomy feedings prompting subsequent referral for fundoplication. After surgery, clinical evaluation of GER was conducted at all postoperative visits. None of the parents reported clinical evidence of recurrent GER in the children after fundoplication.
2.4. Nutritional status The mean preoperative weight-for-age and weight-forlength of these infants were the 11th and 15th percentiles, respectively. After surgery, all subjects gained weight. The average weight gain among the children was 3.36 kg (range, −1.8 to 4.1). Mean weight-for-age percentile of the children more than doubled postoperatively (P = .01). Fig. 1 represents the change in mean weight-for-length percentile for each of the subjects, which increased postoperatively from the 14th percentile to the 27th percentile (P = .03).
2.5. Pre- and postoperative hospitalization rate Inherent in the decision to pursue antireflux surgery is the goal of reducing aspiration-related events that contribute a great deal of morbidity and mortality to children with SMA type I. This was evidenced by the finding that 6 (50%) of the children in this study were hospitalized a total of 11 times in the 12 months preceding operation. Nearly all of these illnesses resulted in intensive care unit admissions for respiratory complications, and 2 children required
Early laparoscopic fundoplication and gastrostomy in infants
Fig. 1 Body weight-for-length percentiles for children with SMA type I after surgery. Mean weight-for-length percentile is shown for the cohort both pre- and postoperatively. Preoperative growth parameters shown are those recorded for each child at the time of operation. Postoperative growth parameters were assessed at each subsequent visit but are reported here at 12 months postoperatively or the most recent follow-up visit if 12-month data were not yet available.
endotracheal intubation. Table 3 summarizes the pre- and postoperative hospitalizations for the cohort. As shown, 4 (33%) children were hospitalized in the 12 months after surgery: 3 for respiratory distress and 1 for bronchiolitis. The total number of hospitalizations in the cohort decreased nearly 50% postoperatively; however, this difference did not reach statistical significance because of the overall low number of events (P = .34). Although the reasons for hospitalization remained respiratory-related in all cases, none of the children required invasive ventilation during this time.
3. Discussion Children with SMA type I pose a special challenge to physicians managing the nutritional and pulmonary complications of their disorder. Silent and overt GER is common in all children with NMD and is a frequent cause for referral to pediatric surgeons, particularly when the need arises for enteral nutrition access. Several studies have evaluated the outcomes after enterostomy tube placement in children with
2035 NMD and found higher rates of perioperative morbidity (42%), need for reoperation, and a 15% 30-day mortality rate [10,11]. Our study included only children with SMA type I, the most severe phenotype, who are theoretically subject to the highest perioperative complication rate. Despite the added risks of the fundoplication, our observed postoperative mortality rate of zero is far lower than that reported for gastrostomy alone emphasizing the beneficial effect of a concomitant fundoplication. Overall, the surgical and postoperative management approach used in this cohort appeared to be safe with minimal short-term complications (atelectasis in 1 patient) and no long-term complications identified. These improved outcomes may be attributable to the earlystage intervention in most of our patients; however, this is difficult to quantify because a third of the patients in our cohort were clinically asymptomatic for GER at the time of operation. Nonetheless, the reported natural history of SMA ensures that virtually all patients will eventually develop clinically significant GER at some point in their disease course [5]. Patients underwent a UGI evaluation postoperatively at 6 weeks and 1 year. It is the opinion of the authors that postoperative UGI studies greatly assist in both the evaluation and decision-making process with patients with SMA during subsequent respiratory-related hospital admissions. Upper lobe atelectasis and pneumonia are chronic problems for many of these children and likely relate to chronic aspiration of oral secretions; however, the need to rule out recurrent GER frequently arises [4]. Given the high rate of silent reflux-related aspiration events, history alone is likely inadequate. A UGI at 6 weeks postoperatively documents the postoperative appearance of fundoplication for comparison as needed. A follow-up study at 12 months confirms the integrity of the fundoplication and can be used as a comparison to the 6-week study to assess any changes in the anatomy of the fundoplication that may indicate a loosening of the wrap. Patients with SMA are subject to a particularly high morbidity associated with silent GER, and the first indication of recurrent reflux may indeed be a lifethreatening pneumonia. Alternatively, pH or impedance probe monitoring could be used to evaluate for recurrent reflux but may be more technically challenging in this patient population given their need for multiple daily BiPAP treatments. Although the significance of the decline was limited by the small size of the cohort, a 50% decrease was observed in the number of respiratory-related hospitalizations in the first 12 months postoperatively. This reduction is likely attributable to the addition of an antireflux procedure at the time of gastrostomy placement. Wales et al [10] have previously studied the impact of open gastric fundoplication and gastrostomy vs gastrostomy alone in neurologically impaired children. The authors demonstrated that significant aspiration-related respiratory events decreased from 30%-50% to 15%-17% postprocedure in children who underwent fundoplication.
2036
E.T. Durkin et al.
Table 3
Pre- and postoperative hospitalizations
Patient
Preoperative hospitalizations (12 mo)
1 2 3 4 5 6 7 8 9 10 11 12 Total
0 1 0 0 2 0 1 0 1 2 4 0 11
Precipitating factor
Postoperative hospitalizations (12 mo)
RD
Dehydration, RD Pneumoniaa, Influenza RD RD a
b
0 2 0 0 0 0 1 1 0 2 0 0 6
Precipitating factor
RD
RSV bronchiolitis RD RD
RD indicates respiratory distress; RSV, respiratory syncytial virus. a Mechanical ventilation required at one or more hospitalizations. b Confirmed by chest x-ray.
When comparing the number of pre- and postoperative hospitalizations in the current series, there was an apparent decline in the severity of these encounters as indicated by the need for mechanical ventilatory support. Despite the chronological progression of their disease, these infants remained free from significant respiratory or other illnesses. The reasons for this are likely multifactorial and related not only to the elimination of GER and silent reflux-associated aspiration but also to improved nutritional status and better respiratory care. Although, not part of our approach, a sialoadenectomy could be considered for children who experience a significant amount of aspiration related to oropharyngeal secretions [13]. Nutritional parameters such as weight-for-age and weight-for-length percentiles often provide easily accessible
information about a child's overall nutritional status and therefore functional status in children with NMD. Most of the children in this series gained weight over the 12 months after placement of the gastrostomy tube and initiation of enteral nutrition. The average weight-for-length percentile significantly increased from 14.5% to 26.7% after our intervention (P = .01). Although age-specific comparisons, such as growth percentiles, are imperfect assessments for children with SMA because of their reduced muscle mass and increased fat-to-muscle ratio, they do represent a practical way to track the adequacy of nutritional supplementation [9]. Alternatives to these types of measurements include the use of skinfold caliper measurements or bone mineral content, data which were not available in the subjects whose records we reviewed.
Fig. 2 Multidisciplinary management protocol for patients with SMA. This table outlines the general pre- and postoperative management strategy for all patients with SMA at our institution. Specific emphasis is placed on coordination of an efficient system of multidisciplinary care.
Early laparoscopic fundoplication and gastrostomy in infants One limitation of the present study is the absence of an age-matched control group with SMA type I who underwent either open or laparoscopic gastrojejunostomy (GJ) tube placement. Such a cohort would be helpful to determine whether our results were influenced more by early surgical intervention for reflux prevention or by nutritional augmentation alone. However, given the historically poor outcomes in these patients, the addition of the fundoplication seemed necessary. A temporary GJ tube was placed in the 1 patient who presented with a preexisting gastrostomy before performing the fundoplication. However, GJ tubes are a poor long-term option in these patients because they frequently become clogged or displaced resulting in more complicated and ineffective management of the patient's nutrition. Given the current data, the options of gastrostomy alone or GJ are likely best explored in the development of a prospective, randomized multicenter study on this topic. However, the relative rarity of SMA makes establishing a larger cohort of patients limited to those with type I disease particularly difficult and would likely require the collaboration of major pediatric neuromuscular centers caring for children with SMA with similar interventions. Coordination of these multi-institutional studies is one of the major challenges facing investigators treating children with SMA but is essential to provide survival and morbidity data to aid in long-term care decisions [14]. In summary, SMA is a devastating diagnosis for children and their families. As children progress in their disease, they fall farther behind in their sensorimotor development. The findings of this study illustrate that laparoscopic fundoplication in infants with SMA type I carries a very low-risk perioperative morbidity and no observed mortality. Early surgical referral, a minimally invasive operative approach, and a standardized postoperative multidisciplinary plan of care (Fig. 2) likely contributed to a favorable outcome. Although all children with SMA type I may not be suited to such an approach, the proposed framework can be used as a general guide for assessment and management of these children both pre- and postoperatively. After surgery, patients experienced an improved overall nutritional status, which may support respiratory muscle mechanics and
2037 improve secretion clearance. Ultimately, these factors may contribute to a long-term reduction in significant aspiration events. In the future, multi-institutional trials will be needed to provide definitive answers to practical questions regarding the care of children with SMA.
References [1] Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics 2004;114:e548-53. [2] Iannaccone ST. Spinal muscular atrophy. Semin Neurol 1998;18: 19-26. [3] Hausmanowa-Petrusewicz I, Vrbova G. Spinal muscular atrophy: a delayed development hypothesis. Neuroreport 2005;16:657-61. [4] Birnkrant DJ. The assessment and management of the respiratory complications of pediatric neuromuscular diseases. Clin Pediatr 2002; 41:301-8. [5] Birnkrant DJ, Pope JF, Martin JE, et al. Treatment of type I spinal muscular atrophy with noninvasive ventilation and gastrostomy feeding. Pediatr Neurol 1998;18:407-10. [6] Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 2007;22: 1027-49. [7] Innaccone ST, Burghes A, Pourmand R, et al. Spinal muscular atrophies. Neuromuscular Disorders. Philadelphia: Lippencott Williams & Williams; 2001. p. 83-98. [8] Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol 2007;22:957-66. [9] Tilton AH, Miller MD, Khoshoo V. Nutrition and swallowing in pediatric neuromuscular patients. Sem Pediatr Neurol 1998;5:106-15. [10] Wales PW, Diamond IR, Dutta S, et al. Fundoplication and gastrostomy versus image-guided gastrojejunal tube for enteral feeding in neurologically impaired children with gastroesophageal reflux. J Pediatr Surg 2002;37:407-12. [11] Sy K, Mahant S, Taback N, et al. Enterostomy tube placement in children with spinal muscular atrophy type 1. J Pediatr 2006;149: 837-9. [12] Yuan N, Wang CH, Trela A, et al. Laparoscopic Nissen fundoplication during gastrostomy tube placement and noninvasive ventilation may improve survival in type I and severe type II spinal muscular atrophy. J Child Neurol 2007;22:727-31. [13] Becmeur F, Horta-Geraud P, Brunot B, et al. Diversion of salivary flow to treat drooling in patients with cerebral palsy. J Pediatr Surg 1996;31: 1629-33. [14] Crawford TO. Concerns about the design of clinical trials for spinal muscular atrophy. Neuromuscul Disord 2004;14:456-60.
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Early laparoscopic fundoplication and gastrostomy in infants with spinal muscular atrophy type I Emily T. Durkin a , Mary K. Schroth b , Margaret Helin a , Aimen F. Shaaban c,⁎ a
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375, USA Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA c Department of Surgery, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA b
Received 24 January 2008; revised 5 May 2008; accepted 21 May 2008
Key words: Neuromuscular disorders; Nutrition; Aspiration; Morbidity/Mortality; Enteral feeding
Abstract Background/Purpose: Spinal muscular atrophy (SMA) in children leads to progressive muscle weakness, dysphagia, aspiration, and death. We hypothesized that early laparoscopic fundoplication and gastrostomy in infants with SMA type I could be performed safely perhaps leading to fewer aspiration events and improved nutritional status. Methods: Children diagnosed with SMA type I from 2002 through 2005 were included (n = 12). All children underwent laparoscopic Nissen fundoplication with gastrostomy shortly after diagnosis. Postoperative respiratory management and discharge criteria were standardized. Results: All patients were extubated immediately postoperatively. There were no significant complications. Average time to full feeding and inpatient length of stay were 42 ± 4.9 hours (range, 30-48 hours) and 78 ± 22.5 hours (range, 44-120 hours), respectively. Mean weight-for-length percentile was doubled at 1 year postoperatively (P = .03). The number of respiratory-related hospitalizations in the cohort decreased by almost 50% in the ensuing 12 months after surgery, although this did not reach statistical significance in this small cohort (P = .34). Conclusions: Early laparoscopic fundoplication and gastrostomy is safe and is associated with improved nutritional status. A trend toward fewer significant long-term aspiration-related events was seen after fundoplication. To better assess the long-term benefits of performing an antireflux procedure in these high-risk patients, a larger prospective trial comparing current nutritional support practices is needed. © 2008 Elsevier Inc. All rights reserved.
Spinal muscular atrophy (SMA) is an autosomal recessive neurological disease that affects 1 in 6000 to 10,000 children and is caused by degeneration of the anterior horn cells in the spinal cord [1]. The most common and severe form of SMA is designated as type I, also known as Werdnig-Hoffman Disease or Floppy Baby syndrome. Children affected with ⁎ Corresponding author. Tel.: +1 608 263 9419; fax: +1 608 263 7652. E-mail address: [email protected] (A.F. Shaaban). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.05.035
SMA type I typically display the most severe neurological findings with generalized weakness appearing within the first 3 months of life. Bulbar dysfunction is universal in these patients and typically leads to feeding and swallowing difficulties, which result in aspiration pneumonia and eventual death [2]. Ninety-eight percent of children with SMA have homozygous deletion of the survival motor neuron 1 (SMN1) gene located on chromosome 5q13 [3]. The diagnosis of SMA is
2032 typically made in conjunction with physical examination findings and genetic testing for SMN gene deletion or mutation [4,5]. Traditionally, SMA has been designated into 3 types based upon the age of onset: type I is associated with symptom onset before age 6 months; type II is associated with symptom onset after age 6 months and before 18 months; and type III is associated with symptom onset after age of 18 months [2]. Recently, the International SMA Consortium significantly revised this classification system and reclassified affected individuals based on age at onset of symptoms, highest motor function achieved, and age of death [6]. The natural history of SMA type I is such that 80% of children will die within the first year of life [7]. However, in centers that routinely care for children with complex neuromuscular disorders (NMDs), the life expectancy for children with SMA type I has been extended from less than 1 year to more than 2 years of age [8]. Advances in airwayclearance, noninvasive ventilatory support and nutritional supplementation have likely led to this improved survival. In addition, systematic integration of pediatric subspecialty management, as recommended by the International SMA Consortium, greatly enhances the care of these patients [6]. Nutritional support for patients with SMA type I remains a clinical challenge without a clear consensus in the available literature. Children with SMA type I in particular tire early during feedings and quickly become unable to achieve adequate caloric intake to prevent weight loss resulting in worsening muscle atrophy. As the disease progresses, bulbar dysfunction, respiratory muscle fatigue, and malnutrition lead to aspiration events and recurrent respiratory tract infections, each of which can potentially become a lifethreatening pneumonia [9]. Although elimination of oral nutritional intake decreases the possibility of oropharyngeal aspiration, gastroesophageal reflux (GER) can still occur in these children. The true incidence of clinically significant GER in patients with SMA type I is unknown; however, it has been reported to be as high as 100% in some series [4,5]. Several studies have evaluated gastrostomy feeding without a concomitant antireflux procedure in patients with SMA in the setting of medically treated GER and have reported high rates of postoperative aspiration pneumonia and death [10,11]. A review of these reports suggest that patients with SMA type I are poor candidates for antireflux operations because of their high perioperative risk, overall poor prognosis, and short life expectancy. Presently, there is little information available in the literature to contradict this conclusion. Only 1 study to date has evaluated the outcome of patients with SMA undergoing antireflux procedures [12]. Unfortunately, this study did not evaluate type I patients, specifically those who are theoretically subject to the highest perioperative risks. Furthermore, the timing of surgical intervention was not specifically evaluated with regard to prevention of GER in SMA patients. The goal of the current study was to assess the risks and benefits of early referral for an antireflux
E.T. Durkin et al. procedure shortly after diagnosis in children with SMA type I. We hypothesized that a minimally invasive procedure coupled with an aggressive postoperative extubation and airway clearance strategy could be accomplished safely, improve patients' nutritional status, and perhaps reduce future aspiration events.
1. Methods 1.1. Subjects After receiving institutional review board approval, we reviewed the records of children diagnosed with SMA type I at our institution from 2003 to 2005. All patients newly diagnosed with SMA type I during this time were referred for surgical evaluation. At the time of surgical consultation, patients were clinically evaluated for GER by obtaining a detailed history about reflux-related events such as colicky pain episodes, irritability, frequent spitting up, poor sleep habits, frequent waking, and vomiting more than 1 hour after feeds. Patients were evaluated radiographically for the presence of aspiration by a video swallowing study performed by trained pediatric speech pathology personnel. A preoperative barium upper gastrointestinal (UGI) series was obtained to ensure normal gastric anatomy and intestinal rotation before operative intervention. The number of, and precipitating factors for, all preoperative hospitalizations were noted. Patients' baseline length and weight were recorded at all preoperative visits and at the time of surgery.
1.2. Surgical procedure All patients underwent laparoscopic fundoplication and gastrostomy by the same experienced laparoscopic surgeon using an identical technique. An opiate-free general anesthetic was administered, and all patients received a “single-shot” caudal epidural. A 5-trocar method was used. The short gastric vessels were divided, and a hiatal repair was performed in all cases. An esophageal bougie was used to gauge the caliber of the 360° fundoplication, which was 2.5 cm in length. No procedures were converted to an open technique. After fundoplication, a percutaneous gastrostomy was created, and a gastrostomy button catheter placed primarily. All patients were extubated immediately postoperatively. Given the high risk of significant postanesthesia atelectasis, patients were observed for 24 hours after surgery in the pediatric intensive care unit with continuous cardiopulmonary monitoring.
1.3. Postoperative respiratory care and feeding After the procedure, patients were extubated to highspan inspiratory-expiratory positive airway pressure (IPAPEPAP) ≥10 bilevel positive airway pressure (BiPAP) per
Early laparoscopic fundoplication and gastrostomy in infants nasal mask ventilation and received every 4 hours airway clearance with chest physiotherapy. This was followed by mechanical insufflation-exsufflation, postural drainage, and mechanical insufflation-exsufflation again. Postoperative pain management consisted of scheduled acetaminophen and intravenous ketorolac for 48 hours. Narcotics were administered as needed for pain control. Patients were jointly managed by the surgical and pulmonary services during their hospitalization. All children were initiated on enteral feeding via gastrostomy at 24 hours postoperatively. Nutritional requirements were calculated to provide 100% of each subject's daily caloric requirement. Half of this requirement was administered during the day in the form of bolus feeds every 3 hours fed by gravity with continuous venting of the gastrostomy to an open syringe. The remainder was administered continuously over 10 hours at night via infusion pump also with continuous venting of the gastrostomy. Patients were initiated at 50% of their total daily requirements and advanced to goal requirements by the second postoperative day. During enteral feeding advancement, all subjects were observed closely for signs of feeding intolerance such as bloating, retching, or abdominal pain. Gastrostomy tubes were continuously vented for the first 2 weeks postoperatively, then progressively clamped until only vented pre- and postfeeding for 30 minutes and while on BiPAP support. Venting of the gastrostomy tubes postfundoplication was done to reduce gastric bloating resulting from the BIPAP treatments that all children received. Patients were discharged from the hospital when they tolerated goal gastrostomy feedings with regular bowel movements and had returned to their preoperative regimen of BiPAP use.
2033 hospitalizations were compared pre- and postoperatively using a 2-tailed Student t test assuming unequal variables. P values ≤.05 were considered significant.
2. Results 2.1. Subjects A total of 15 children were diagnosed with SMA of any type, all confirmed by genetic analysis, between January 2002 and December 2005 at our institution. Surgical referral was made immediately at the time of diagnosis in most cases to study the effect of early intervention for the prevention of GER. Therefore, for the purposes of inclusion in this study, children were classified as having SMA type I if the onset of symptoms began before 6 months of age rather than by the highest motor function achieved. Twelve children met this criterion and were ultimately included in the analysis. Table 1 summarizes the demographics of the study cohort. The average age at diagnosis was 6.2 months (range, 1-9 months), and all children included had symptoms present before diagnosis consistent with the most severe SMA phenotype. An attempt was made in all cases to intervene surgically as soon as possible after the diagnosis of SMA type I was established. Although early surgical referral was made in all cases, preoperative delays were occasionally encountered because of recovery from acute respiratory illness, transfer from outside institutions, and parental scheduling limitations. Ultimately, patients underwent surgery at an average age of 10.1 months (range, 5-14 months).
2.2. Surgical procedure and perioperative results 1.4. Complications and follow-up care Complications were defined as short-term if they occurred less than 30 days following operation and included reintubation for any reason after surgery, significant intraoperative or postoperative bleeding, clinically documented infection, oxygen requirement greater than 24 hours after surgery, prolonged ileus, and clinically or radiographically documented pneumonia. Long-term complications were defined as any complication that occurred more than 30 days postoperatively as a consequence of surgical intervention. Clinical GER symptoms were assessed routinely at all postoperative visits. A baseline UGI was obtained at 6 weeks postoperatively. Growth parameter measurements were obtained at all subsequent clinic visits.
1.5. Statistical methods Averages and ranges were calculated for all categorical variables. Body measurement parameters and number of
All children underwent laparoscopic Nissen fundoplication and feeding gastrostomy placement under general anesthesia in an identical manner performed by the same Table 1
Patient demographics
Patient
Sex
Age at diagnosis (mo)
Age at operation (mo)
1 2 3 4 5 6 7 8 9 10 11 12 Mean ± SD
Male Male Male Female Female Female Male Male Female Female Male Female 50% male
4 4 9 6 1 8 6 6 8 8 9 6 6.2 ± 2.4
11 7 14 12 5 14 9 8 10 12 13 8 10.1 ± 2.9
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Table 2
Perioperative outcomes
Patient
Operative time (min)
Narcotic doses required
Oxygen saturation 4 h (%)
Oxygen saturation 24 h (%)
Time to initiation of feeds (h)
Time to full feeds (h)
Time to first BM (h)
LOS (h)
Complication
1 2 3 4 5 6 7 8 9 10 11 12 Mean
195 135 165 150 173 155 161 193 144 274 161 206 176 ± 38
0 0 1 0 0 0 0 0 0 0 1 0 b1 dose
100 97 100 99 99 96 97 95 99 96 100 97 98 ± 1.8
100 100 99 94 99 95 98 99 97 100 100 95 98 ± 2.2
24 21 22 24 24 22 22 26 21 24 23 20 23 ± 1.7
45 45 41 44 42 46 30 42 45 48 45 35 42 ± 5.1
45 28 42 47 41 48 54 24 34 28 28 45 39 ± 9.8
48 70 44 96 120 60 79 75 74 72 106 74 77 ± 22
– – – – L lung atalectasis – – – – – – – b1
BM indicates bowel movement; LOS, length of stay.
surgeon. Table 2 outlines the perioperative outcome measurements for each patient. Mean operative time was 176 ± 38.6 minutes. All children were extubated immediately postoperatively and transitioned to BiPAP support in the operating room. No patient required reintubation for any reason. The mean oxygen saturation at 4, 12, and 24 hours postoperatively was 98% at each time-point for all children. No child required supplemental oxygen longer than 24 hours. Opioid analgesia in the form of intravenous morphine sulfate was required by only 2 of the children, who each received 1 dose. The average time to full feeds was 42 ± 5.1 hours (range, 30-48), and the average time to first bowel movement was 39 ± 9.8 hours (range, 24-54). One patient was noted to have significant left lung atelectasis on the first postoperative evening, which was diagnosed when a routine postoperative chest x-ray was performed. This patient was managed conservatively with airway clearance measures, identical to those outlined in the Methods section, and a second chest x-ray performed 12 hours later showed complete resolution of the atelectasis. No long-term complications were identified in any of the subjects during the period evaluated. The average length of stay was 77 ± 22 hours (range, 44120). The median length of follow-up was 10.3 ± 7.8 months (range, 1-22 months), and the mean age of the children at that time was 20.8 months (n = 11). The current mean age of the children is 28 months. One child in the series has since died from progressive respiratory failure, unrelated to aspiration, as a result of her disease.
2.3. Aspiration and GER symptom assessment Previous reports have documented a high rate of swallowing disorders in patients with SMA; therefore, this was routinely assessed clinically at the time of surgical
referral [9]. All of the children who underwent video swallow study (9/9) displayed abnormal findings ranging from delayed swallowing to severe oropharyngeal aspiration. Clinical evidence of GER was established preoperatively by history in 8 (66%) of 12 patients. Patient 10 had a previous percutaneous endoscopic gastrostomy without a concomitant fundoplication. This patient's GER symptoms dramatically worsened after initiating gastrostomy feedings prompting subsequent referral for fundoplication. After surgery, clinical evaluation of GER was conducted at all postoperative visits. None of the parents reported clinical evidence of recurrent GER in the children after fundoplication.
2.4. Nutritional status The mean preoperative weight-for-age and weight-forlength of these infants were the 11th and 15th percentiles, respectively. After surgery, all subjects gained weight. The average weight gain among the children was 3.36 kg (range, −1.8 to 4.1). Mean weight-for-age percentile of the children more than doubled postoperatively (P = .01). Fig. 1 represents the change in mean weight-for-length percentile for each of the subjects, which increased postoperatively from the 14th percentile to the 27th percentile (P = .03).
2.5. Pre- and postoperative hospitalization rate Inherent in the decision to pursue antireflux surgery is the goal of reducing aspiration-related events that contribute a great deal of morbidity and mortality to children with SMA type I. This was evidenced by the finding that 6 (50%) of the children in this study were hospitalized a total of 11 times in the 12 months preceding operation. Nearly all of these illnesses resulted in intensive care unit admissions for respiratory complications, and 2 children required
Early laparoscopic fundoplication and gastrostomy in infants
Fig. 1 Body weight-for-length percentiles for children with SMA type I after surgery. Mean weight-for-length percentile is shown for the cohort both pre- and postoperatively. Preoperative growth parameters shown are those recorded for each child at the time of operation. Postoperative growth parameters were assessed at each subsequent visit but are reported here at 12 months postoperatively or the most recent follow-up visit if 12-month data were not yet available.
endotracheal intubation. Table 3 summarizes the pre- and postoperative hospitalizations for the cohort. As shown, 4 (33%) children were hospitalized in the 12 months after surgery: 3 for respiratory distress and 1 for bronchiolitis. The total number of hospitalizations in the cohort decreased nearly 50% postoperatively; however, this difference did not reach statistical significance because of the overall low number of events (P = .34). Although the reasons for hospitalization remained respiratory-related in all cases, none of the children required invasive ventilation during this time.
3. Discussion Children with SMA type I pose a special challenge to physicians managing the nutritional and pulmonary complications of their disorder. Silent and overt GER is common in all children with NMD and is a frequent cause for referral to pediatric surgeons, particularly when the need arises for enteral nutrition access. Several studies have evaluated the outcomes after enterostomy tube placement in children with
2035 NMD and found higher rates of perioperative morbidity (42%), need for reoperation, and a 15% 30-day mortality rate [10,11]. Our study included only children with SMA type I, the most severe phenotype, who are theoretically subject to the highest perioperative complication rate. Despite the added risks of the fundoplication, our observed postoperative mortality rate of zero is far lower than that reported for gastrostomy alone emphasizing the beneficial effect of a concomitant fundoplication. Overall, the surgical and postoperative management approach used in this cohort appeared to be safe with minimal short-term complications (atelectasis in 1 patient) and no long-term complications identified. These improved outcomes may be attributable to the earlystage intervention in most of our patients; however, this is difficult to quantify because a third of the patients in our cohort were clinically asymptomatic for GER at the time of operation. Nonetheless, the reported natural history of SMA ensures that virtually all patients will eventually develop clinically significant GER at some point in their disease course [5]. Patients underwent a UGI evaluation postoperatively at 6 weeks and 1 year. It is the opinion of the authors that postoperative UGI studies greatly assist in both the evaluation and decision-making process with patients with SMA during subsequent respiratory-related hospital admissions. Upper lobe atelectasis and pneumonia are chronic problems for many of these children and likely relate to chronic aspiration of oral secretions; however, the need to rule out recurrent GER frequently arises [4]. Given the high rate of silent reflux-related aspiration events, history alone is likely inadequate. A UGI at 6 weeks postoperatively documents the postoperative appearance of fundoplication for comparison as needed. A follow-up study at 12 months confirms the integrity of the fundoplication and can be used as a comparison to the 6-week study to assess any changes in the anatomy of the fundoplication that may indicate a loosening of the wrap. Patients with SMA are subject to a particularly high morbidity associated with silent GER, and the first indication of recurrent reflux may indeed be a lifethreatening pneumonia. Alternatively, pH or impedance probe monitoring could be used to evaluate for recurrent reflux but may be more technically challenging in this patient population given their need for multiple daily BiPAP treatments. Although the significance of the decline was limited by the small size of the cohort, a 50% decrease was observed in the number of respiratory-related hospitalizations in the first 12 months postoperatively. This reduction is likely attributable to the addition of an antireflux procedure at the time of gastrostomy placement. Wales et al [10] have previously studied the impact of open gastric fundoplication and gastrostomy vs gastrostomy alone in neurologically impaired children. The authors demonstrated that significant aspiration-related respiratory events decreased from 30%-50% to 15%-17% postprocedure in children who underwent fundoplication.
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Table 3
Pre- and postoperative hospitalizations
Patient
Preoperative hospitalizations (12 mo)
1 2 3 4 5 6 7 8 9 10 11 12 Total
0 1 0 0 2 0 1 0 1 2 4 0 11
Precipitating factor
Postoperative hospitalizations (12 mo)
RD
Dehydration, RD Pneumoniaa, Influenza RD RD a
b
0 2 0 0 0 0 1 1 0 2 0 0 6
Precipitating factor
RD
RSV bronchiolitis RD RD
RD indicates respiratory distress; RSV, respiratory syncytial virus. a Mechanical ventilation required at one or more hospitalizations. b Confirmed by chest x-ray.
When comparing the number of pre- and postoperative hospitalizations in the current series, there was an apparent decline in the severity of these encounters as indicated by the need for mechanical ventilatory support. Despite the chronological progression of their disease, these infants remained free from significant respiratory or other illnesses. The reasons for this are likely multifactorial and related not only to the elimination of GER and silent reflux-associated aspiration but also to improved nutritional status and better respiratory care. Although, not part of our approach, a sialoadenectomy could be considered for children who experience a significant amount of aspiration related to oropharyngeal secretions [13]. Nutritional parameters such as weight-for-age and weight-for-length percentiles often provide easily accessible
information about a child's overall nutritional status and therefore functional status in children with NMD. Most of the children in this series gained weight over the 12 months after placement of the gastrostomy tube and initiation of enteral nutrition. The average weight-for-length percentile significantly increased from 14.5% to 26.7% after our intervention (P = .01). Although age-specific comparisons, such as growth percentiles, are imperfect assessments for children with SMA because of their reduced muscle mass and increased fat-to-muscle ratio, they do represent a practical way to track the adequacy of nutritional supplementation [9]. Alternatives to these types of measurements include the use of skinfold caliper measurements or bone mineral content, data which were not available in the subjects whose records we reviewed.
Fig. 2 Multidisciplinary management protocol for patients with SMA. This table outlines the general pre- and postoperative management strategy for all patients with SMA at our institution. Specific emphasis is placed on coordination of an efficient system of multidisciplinary care.
Early laparoscopic fundoplication and gastrostomy in infants One limitation of the present study is the absence of an age-matched control group with SMA type I who underwent either open or laparoscopic gastrojejunostomy (GJ) tube placement. Such a cohort would be helpful to determine whether our results were influenced more by early surgical intervention for reflux prevention or by nutritional augmentation alone. However, given the historically poor outcomes in these patients, the addition of the fundoplication seemed necessary. A temporary GJ tube was placed in the 1 patient who presented with a preexisting gastrostomy before performing the fundoplication. However, GJ tubes are a poor long-term option in these patients because they frequently become clogged or displaced resulting in more complicated and ineffective management of the patient's nutrition. Given the current data, the options of gastrostomy alone or GJ are likely best explored in the development of a prospective, randomized multicenter study on this topic. However, the relative rarity of SMA makes establishing a larger cohort of patients limited to those with type I disease particularly difficult and would likely require the collaboration of major pediatric neuromuscular centers caring for children with SMA with similar interventions. Coordination of these multi-institutional studies is one of the major challenges facing investigators treating children with SMA but is essential to provide survival and morbidity data to aid in long-term care decisions [14]. In summary, SMA is a devastating diagnosis for children and their families. As children progress in their disease, they fall farther behind in their sensorimotor development. The findings of this study illustrate that laparoscopic fundoplication in infants with SMA type I carries a very low-risk perioperative morbidity and no observed mortality. Early surgical referral, a minimally invasive operative approach, and a standardized postoperative multidisciplinary plan of care (Fig. 2) likely contributed to a favorable outcome. Although all children with SMA type I may not be suited to such an approach, the proposed framework can be used as a general guide for assessment and management of these children both pre- and postoperatively. After surgery, patients experienced an improved overall nutritional status, which may support respiratory muscle mechanics and
2037 improve secretion clearance. Ultimately, these factors may contribute to a long-term reduction in significant aspiration events. In the future, multi-institutional trials will be needed to provide definitive answers to practical questions regarding the care of children with SMA.
References [1] Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics 2004;114:e548-53. [2] Iannaccone ST. Spinal muscular atrophy. Semin Neurol 1998;18: 19-26. [3] Hausmanowa-Petrusewicz I, Vrbova G. Spinal muscular atrophy: a delayed development hypothesis. Neuroreport 2005;16:657-61. [4] Birnkrant DJ. The assessment and management of the respiratory complications of pediatric neuromuscular diseases. Clin Pediatr 2002; 41:301-8. [5] Birnkrant DJ, Pope JF, Martin JE, et al. Treatment of type I spinal muscular atrophy with noninvasive ventilation and gastrostomy feeding. Pediatr Neurol 1998;18:407-10. [6] Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 2007;22: 1027-49. [7] Innaccone ST, Burghes A, Pourmand R, et al. Spinal muscular atrophies. Neuromuscular Disorders. Philadelphia: Lippencott Williams & Williams; 2001. p. 83-98. [8] Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol 2007;22:957-66. [9] Tilton AH, Miller MD, Khoshoo V. Nutrition and swallowing in pediatric neuromuscular patients. Sem Pediatr Neurol 1998;5:106-15. [10] Wales PW, Diamond IR, Dutta S, et al. Fundoplication and gastrostomy versus image-guided gastrojejunal tube for enteral feeding in neurologically impaired children with gastroesophageal reflux. J Pediatr Surg 2002;37:407-12. [11] Sy K, Mahant S, Taback N, et al. Enterostomy tube placement in children with spinal muscular atrophy type 1. J Pediatr 2006;149: 837-9. [12] Yuan N, Wang CH, Trela A, et al. Laparoscopic Nissen fundoplication during gastrostomy tube placement and noninvasive ventilation may improve survival in type I and severe type II spinal muscular atrophy. J Child Neurol 2007;22:727-31. [13] Becmeur F, Horta-Geraud P, Brunot B, et al. Diversion of salivary flow to treat drooling in patients with cerebral palsy. J Pediatr Surg 1996;31: 1629-33. [14] Crawford TO. Concerns about the design of clinical trials for spinal muscular atrophy. Neuromuscul Disord 2004;14:456-60.