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The surgical management of children with familial dysautonomia
The Surgical Management of Children With Familial Dysautonomia By Itzhak Vinograd, Raphael Udassin, Benzion Beilin, Abraham Neuman, Chani Maayan, and Shemuel Nissan
Jerusalem, Israel 9 Familial dysautonomia (FD) is a rare incurable genetic disorder w i t h multisystem involvement. Most of its clinical manifestations are related to disorders of the autonomic nervous system. The disease is associated w i t h specific disturbances of the upper gastrointestinal tract: pharyngoesophageal dyskinesia, gastroesophageal reflux, and prolonged gastric emptying. About 40% of the dysautonomic children manifest repeat vomiting crises. In view of the extensive gastrointestinal symptomatology, children with FD are prone to repeated aspiration pneumonia and chronic respiratory failure, while inadequate calory and fluid intake may lead to a chronic state of hypovolemia and severe failure to thrive. Control of vomiting, prevention of aspiration due to abnormal swallowing, and the assurance of adequate calory intake are three major objectives in the treatment of the dysautonomic child. Medical treatment of the gastrointestinal disorders using different drugs has had limited success. This study reviews the surgical experience in ten children with FD. The type of the procedure used was determined by the severity of the upper GI disturbances. Nine children underwent gastroesophageal Nissen fundoplication and gastrostomy. In seven of them, a pyloroplasty was added. Gastrostomy alone was done in one patient only. Postoperative complications included transient dysphagia in four patients, gastric dilatation in four patients, and dumping syndrome in one. There has been no incidence of immediate postoperative death, One child died 6 months after operation from severe and irreversible respiratory failure. Following operation, the patients still suffered f r o m dysautonomic crises but these were not associated with vomiting, Pneumonia was eliminated in four children and in five, the incidence of pneumonia was reduced significantly. In s e v e n children, a consistent weight gain was achieved after a short period of adaptibUity. The surgical procedure does not eliminate the dysautonomic crises, yet it does change the quality of life and by reducing the incidence of pneumonia it should have a major effect on the life span in FD patients. 9 1985 by Grune & Stratton, Inc. I N D E X W O R D S : Familial dysautonomia; fundoplication; gastroesophageal reflux.
~AMILIAL D Y S A U T O N O M I A (FD) is a rare incurable genetic disorder with multisystem involvement. The most striking manifestations appear
F
From the Departments of Pediatric Surgery, Anesthesia, and Pediatrics, Hadassah University Hospital, Mount-Scopus, Jerusalem. Presented before the 16th Annual Meeting of the American Pediatric Surgical Association, Kohala Coast, Hawaii, May 1-4, 1985. Address reprint requests to Itzhak Vinograd, MD, Pediatric Surgery Department, Hadassah University Hospital, MountScopus, 91240 Jerusalem, Israel. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2006-0012503.00/0 632
to be disorders of the autonomic system, such as diminished lacrimation, hyperhydrosis, labile blood pressure, derangement of temperature control, and relative insensitivity to pain. Other prominent features are emotional instability and morning nausea) The disease is associated with specific disturbances of the upper gastrointestinal tract; pharngoesophageal dyskinesia, 1abnormal esophageal motility,2 decreased lower esophageal sphincter pressure, 2 abnormal motility of the antrum? and pylorospasm. 2 These result in aspiration of oral feeding and gastroesophageal reflux that is aggravated by prolonged gastric emptying. In addition, about 40% of the dysautonomic children manifest vomiting crises4: repeated, often cyclical vomiting, occurs without any well-understood cause. The typical attack lasts 24 to 72 hours with retching and vomiting as often as every 15 to 20 minutes. The attacks are associated with high blood pressure, perspiration, and red blotching of the skin. In view of the extensive gastrointestinal symptomatology, children with FD are prone to repeated aspiration pneumonia. Inadequate calory and fluid intake may lead to a severe failure to thrive and to a chronic state of hypovolemia. In recent prospective survival study in FD patients, 5 pulmonary complications were the most frequent cause of death. Medical treatment of the gastrointestinal disorders had limited S u c c e s s . 6 Control of vomiting and its life-threatening complications, prevention of aspiration of oral feeding, and adequate calory intake are three critical aims in the treatment of the dysautonomic child. Surgical procedures, such as fundoplication, prevent vomiting; pyloroplasty enables adequate gastric emptying, while gastrostomy may be used for long-term feeding when patients are unable to swallow. Although FD was described as early as 1949, 7 the first attempt of surgical treatment was described in 1982 by Vinograd et al. 8 In the same year, Axelrod et al 9 reported the results of surgical treatment in a larger group of patients. In spite of the extensive information about the clinical manifestations and the experience with medical treatment in FD, there is hardly any data concerning the surgical treatment of this disease. This study reviews our recent experience with the Surgical approach in ten patients with FD. MATERIALS A N D METHODS Ten children with FD who were operated upon in the Pediatric Surgery Service at the Hadassah University Hospital, MountScopus, were evaluated and followed up. The diagnosis of FD was
Journal of Pediatric Surgery. Vo120, No 6 (December), 1985: pp 632-636
SURGICAL MANAGEMENT
OF C H I L D R E N W I T H FD
633
confirmed in all the patients by the distinctive clinical signs of the disease, the absence of flare following intradermal injection of histamine, ~~ absence of fungiform papillae on the tongue, ~ and miosis following instillation of methacholine into the conjunctiva. 12 Preoperatively, all the patients underwent clinical and nutritional assessment. They had radiologic evaluation of the pharyngoesophageal coordination and esophageal and gastric motility studies. Twelve-hour pH monitoring and a milk scan were performed and pulmonary function tests when indicated. The type of the surgical procedure was decided upon by the following criteria: (1) Nissen fundoplication was done for gastroesophageal reflux or cyclic vomiting. (2) Pyloroplasty was performed in patients with pylorospasm or antral dysmotility. (3) Gastrostomy was done for pharyngoesophageal dyskinesia and/or poor nutritional state. Preoperative preparation included intensive pulmonary physiotherapy and deep suction. The performance of a tracheostomy, one week before operation, was considered in children with severe bronchiectasis and poor pulmonary function tests. Broad spectrum antibiotics and cimetidine were given routinely before operation. All the patients received 10 to 20 mL/kg of fresh-frozen plasma on the evening before operation. This was repeated before the induction of anesthesia together with Ringer's lactate solution (5 mL/kg). Premedication consisted of sedation alone (IV Diazepam). Anesthesia was induced and maintained by using the "moderate dose fentanyl" anesthetic technique. ~3At the end of the surgical procedure, residual muscle relaxants and fentanyl-induced respiratory depression were not reversed. All the patients were ventilated until spontaneous ventilation was adequate to permit extubation. When enteral feeding was resumed, the patients were instructed to avoid fluids by mouth and to restrict oral feeding to solids. Fluids were taken through the gastrostomy tube. Whenever the calory intake by mouth was inadequate, it was supplemented by gastrostorey feeding. Follow-up was done regularly. Complete clinical evaluation, nutritional assessment, and postoperative radiologic examinations of the GI tract were carried out.
RESULTS
Ten dysautonomic patients were operated upon during the years 1978 to 1984. There were five males and five females. The mean age at the time of the initial diagnosis of FD was 4.2 years (range, 6 months to 5 years). The mean age at the time of operation was 7.7 years. The youngest patient at the time of operation
was 1.5 years old. Pertinent preoperative clinical findings of major significance are listed in Table 1. Autonomic system disorders were frequent: unstable blood pressure (8 patients), inadequate temperature regulation (5 patients), repeated episodes of breathholding (6 patients), and abnormal EEG in 6 patients, three of whom had overt seizures. Cyclic vomiting crises occurred in 7 patients, two of whom had hematemesis severe enough to require blood transfusions. Moderate to severe scoliosis was found in nine patients. Eight of the patients were in poor nutritional status and in marked growth retardation with both weight and height percentiles of less than 5% before operation. Nine patients had recurrent pneumonia before operation. In seven, the incidence of pneumonia was three or more per six months. The results of the preoperative gastrointestinal assessment and the operative procedures that were performed in each case are summarized in Table 2. Cineesophagograms studies showed objective confirmation of pharyngeoesophageal dyskinesia with aspiration during swallowing in nine patients. The cineesophagograms with the pH monitoring and milk scan confirmed gastroesophageal reflux in nine patients. Delayed gastric emptying was diagnosed in seven patients. In five patients, the radiologic contrast studies showed functional gastric outlet obstruction (pylorospasm). In two patients, the gastric antrum was "funnel shape" and failed to show any evidence of contraction during more than 10 minutes of intermittent fluoroscopic observation. Barium moved by gravity through the pylorus into the duodenum without any evidence of anatomic obstruction. These two pateints were diagnosed as having antral dysmotility. The patients were assigned the following procedures according to the preoperative evaluation: One patient with severe chronic lung disease from repeated aspiraTable 2. P r e o p e r a t i v e Gastrointestinal A s s e s s m e n t and O p e r a t i v e Procedures
Table 1. P r e o p e r a t i v e Clinical Findings in T e n FD P a t i e n t s Nutritional Status
(percentile)
Age at Patient
Sex
Operation
Wt
Ht
GI assessment
Clinicalsymptoms Cyclic Vomiting
Pneumonia*
Patient
PE Dyskinesia
GER
SR
+
+
Operative Procedures
Pylorospasm
Antral Dysmotility
G
F
P
+
--
+
+
+
SR
F
3
<
5%
< 5%
+
--
SM
+
+
+
--
+
§
+
SM
M
7
<
5%
< 5%
+
+ +
SP
--
+
+
--
+
+
+
SP
M
12
<
5%
< 5%
+B
+
KT
+
--
--
--
+
KT
F
1.5
<
5%
< 5%
--
+
DD
+
+
--
--
+
+
--
DD
M
8
50%
< 5%
--
+ +
GZ
+
+
+
--
+
+
+
GZ
M
10
<
5%
<5%
+B
++
KA
+
+
--
+
+
+
+
KA
F
6.5
<
5%
< 5%
+
++
BN
+
+
--
+
+
+
+
BN
M
5
50%
< 5%
+
+ +
SH
+
+
+
--
+
+
+
SH
M
17
<
5%
<5%
+
++
KN
+
+
+
--
+
+
+
KN
F
8
<
5%
< 5%
--
+ +
*+
= 1 t o 2 per 6 too; + + = 3 or m o r e per 6 m o ; + B
associated w i t h severe bleeding.
~ vomiting
A b b r e v i a t i o n s : PE dyskinesia, p h a r y n g e o e s o p h a g e a l dyskinesia; GER, g a s t r o e s o p h a g e a l reflux; G, g a s t r o s t o m y ; plesty.
F, fundoplication;
P, p y l o r o -
634
tion pneumonia underwent a tracheostomy one week before the surgical procedure. Nine patients underwent a Nissen fundoplication and Stamm's gastrostomy. Seven patients with either antral dysmotility or pylorospasm and one patients with neither also had pyloroplasty. Gastrostomy alone was done in one patient. In all ten patients, the operative period was uneventful. Changes in blood pressure and central venous pressure were infrequent and tended to correlate with alterations in heart rate. These changes were responsive to adjustment in the rate of fluid administration. There was no need for exogenous cathecholamines in any of the patients. Postoperatively, the patients were in full consciousness within four to eight hours. Extubation was performed whenever spontaneous ventilation was found to be adequate and usually within six to 14 hours postoperatively. One patient required reintubation for severe bronchospasm that responded to a heavy dose of steroids and bronchodilators. There was no immediate postoperative death. The follow-up period in these children has ranged from 6 months to 7 years (mean, 20.7 months). In seven children, a persistent weight gain was noted after a short adaptation period of 1 to 2 months. Weight gain was marked in four children who adhered to gastrostomy feedings regimen. The occurrence of pneumonia was reduced significantly in all nine patients who had aspiration pneumonia before operation. In four of them, pneumonia was totally eliminated. However, two children with severe bonchiectatic lung disease continued to have occasional episodes of pneumonia. Of these, the patient who had severe and irreversible lung disease and therefore underwent tracheostomy, died six months after the fundoplication. He died because of respiratory failure three months after the removal of the tracheostomy. Two other patients, who repeatedly attempted drinking against advice, also had episodes of pneumonia. In one, the pneumonia recurred shortly after the removal of gastrostomy. The gastrostomy was reluctantly removed due to excessive leakage of gastric fluid and the family objected to its reintroduction. The patient who had only a gastrostomy done, still suffered from pneumonia but at a reduced rate. Symptoms of overt cyclic vomiting as part of the dysautonomic crises were present in seven children before operation. Following operation, the crises continued but were not associated with vomiting. The patient who had placement of a gastrostomy only, developed vomiting attacks six months after operation. In two patients, breath-holding spells stopped following operation. Postoperative complications included transient dys-
VINOGRAD ET AL
phagia in five patients and "gas bloat" in four. The last was relieved by opening the gastrostomy tube. One patient developed postoperatively dumping syndrome that was treated by the reduction of carbohydrates in his diet. Excessive granulation tissue around the gastrostomy tube was a problem in three patients. A repeated UGI series was performed postoperatively in all patients. Gastric reflux was found only in the one patient in whom a gastrostomy alone was performed. In one patient, the fundoplication and the gastric fundus herniated through the hiatus into the lower mediastinum without affecting the competence of the antireflux operation. DISCUSSION
Familial dysautonomia (FD) or Riley-Day syndrome was originally described in 1949. 7 Since then, experience in treatment of FD has broadened considerably. Major advances in the understanding of the pathophysiology and the clinical features brought about a more rational and active approach to the treatment of the disease. However, mortality is still high in FD, particularly during the early years of life. 1 Acute and chronic pulmonary infections, secondary to repeated aspirations, are the most common cause of death, while delayed or inadequate management of vomiting crises and dehydration may have fatal consequences. Surgical treatment that is aimed toward prevention of vomiting, prevention of aspiration due to abnormal swallowing, and toward enabling adequate calory intake may prolong life and improve its quality. There are about 250 patients known to suffer from FD as reported by Axelrod et alS; 66% of them are younger than 20 years. To date, according to the published series, gastrointestinal operation was performed in only 33 patients, g'9 Gastrostomy alone was done in 13 and gastroesophageal fundoplication in 20. Although the results of the surgical treatment in this disease are encouraging, no distinct guidelines have yet been established for the rational approach to the gastrointestinal manifestations in FD. Various types of surgical procedures have been tried in order to prevent vomiting secondary to GER. None had complete success. However, the Nissen fundoplication has proved to be effective and with a relatively low complication rate. 14 In the typically morningnauseated FD child and in FD infants having difficulty in sucking and swallowing, gastrostomy alone was used in order to ensure adequate nutrition.9 The dysautonomic child is able to sense the position of soft food in his mouth but has greater difficulty in doing so in the case of liquids. Gastrostomy feeding can be used until the child learns how to swallow. Meanwhile, solid food should be given orally, since normal speech is related to
SURGICAL MANAGEMENT OF CHILDREN WITH FD
635
normal feeding patterns. The same groups of muscles are involved in both. The combination of pharyngoesophageal dyskinesia and gastroesophageal reflux is very common in FD patients. In the present group, 90% of the children had that combination. It appears that unless megaesophagus, described sometimes in FD patients but not found in our patients, is present, fudoplication and gastrostomy would be the operation of choice. The only patient in this series who underwent gastrostomy alone still suffers from recurrent vomiting and aspiration pneumonia though at a lesser frequency. In the presence of prolonged gastric emptying, a pyloroplasty is also indicated. Timing is of crucial importance in the surgical management of the FD child. Bronchiectasis and pulmonary disease were present in two of our patients. One of them died six months after operation and the other continued to suffer from recurrent pneumonia but to a lesser extent. Recent reviews, in non-FD population, have elaborated on the role of gastroesophageal reflux in the production of chronic pulmonary diseases and have demonstrated that gastroesophageal fundoplication can be of benefit in the treatment of refractory or recurrent pneumonia, failure to thrive, and intractable vomiting. ~4'~5 Cyclic vomiting tends to decrease after puberty in some of the dysautonomic children. But in anticipation that a major part of the pulmonary dam-
age occurs during infancy and early childhood, prevention by an early surgical procedure seems to be rational. In addition, frequent milk aspirations may cause sensitization with mucus production and wheezing on subsequent exposure. General anesthesia was considered to be associated with a considerable risk to the FD patient. However, with the increased understanding of the pathophysiology of dysautonomia and the growing experience with anesthesia in this disease, operations can be performed as indicated regardless of the patient's age. It has been suggested that if swallowing dysfunction coexists with gastroesophageal reflux, then the fundoplication results may not be as favorable. ~4 Evidence for disorders in esophageal motility and pharyngoesophageal dyskinesia exists in many of the dysautonomic patients. Yet, in the present series, the dysphagia was transient and faded with time. The surgical procedure does not eliminate the dysautonomic crises, yet it does change the quality of life and by reducing the incidence of pneumonia it should have a major effect on the life span of FD patients. This experience substantiates the efficacy and relative safety of early surgical treatment, including gastroesophageal fundoplication, gastrostomy, and pyloroplasty in patients with familial dysautonomia.
REFERENCES 1. Axelrod FB, Nachtigal R, Dancis J: Familial dysautonomia: Diagnosis, pathogenesis and management, in Schulman I (ed): Advances in Pediatrics (Vol 21). Chicago, Year Book Medical, 1974, pp 75-96 2. Linde LM, Westover JL: Esophageal and gastric abnormalities in dysautonomia. Pediatrics 29:303-306, 1962 3. Mulvihill S J, Fonkalsrud EW: Pyloroplasty in infancy and childhood. J Pediatr Surg 18:930-936, 1983 4. Riley CM: Familial dysautonomia, in Levine SZ (ed): Advances in Pediatrics (Vol 9). Chicago, Year Book Medical, 1957, pp 157-190 5. Axelrod FB, Abularrage J J: Familial dysautonomia: A prospective study of survival. J Pediatr 101:234-236, 1982 6. Axelrod FB, Branom N, Becker M, et al: Treatment of familial dysautonomia with bethanechol (urecholine). J Pediatr 81:573-578, 1971 7. Riley CM, Day RL, Greeley DMcL, et al: Central autonomic dysfunction with defective lacrimation. Pediatrics 3:468-476, 1949 8. Vinograd I, Lernau OZ, Frand M, et al: Fundoplication and
pyloroplasty--a surgical treatment for intractable "cyclic vomiting" in familial dysautonomia. J Pediatr Surg 17:80-81, 1982 9. Axelrod FB, Schneider KM, Ament ME, et al: Gastroesophageal fundoplication and gastrostomy in familial dysautonomia. Ann Surg 195:253-258, 1982 10. Smith AA, Dancis J: Response to intradermal histamine in familial dysautonomia--a diagnostic sign. J Pediatr 63:889-894, 1963 11. Smith AA, Farhman A, Dancis J: Tongue in familial dysautonomia, a diagnostic sign. Am J Dis Child 110:152-154, 1965 12. Smith AA, Dancis J, Breinin G: Ocular responses to autonomic drugs in familial dysautonomia. Invest Ophtalmol 4:358-361, 1965 13. Beilin B, Maayan Ch, Vatashsky E, et al: Fentanyl anesthesia in familial dysautonomia. Anesth Analg 64:72-76, 1985 14. Leape LL, Ramenofsky ML: Surgical treatment of gastroesophageal reflux in children. Results in Nissen's fundoplication in 100 children. Am J Dis Child 134:935-938, 1980 15. Jolley SG, Herbst J J, Johnson DG, et al: Surgery in children with gastroesophageal reflux and respiratory symptoms. J Pediatr 96:194-198, 1980
Discussion Eric Fonkalsrud (Los Angeles): Dr Vinograd and his colleagues from Jerusalem have compiled the largest single hospital experience in the surgical manage-
ment of these unfortunate children with familial dysautonomia, and are to be congratulated on their excellent results. Neither gastrostomy nor fundoplica-
636
tion cures the dysautonomic crises, as the authors have pointed out; and drug therapy is still required for the systemic manifestations of the disease. However, the vomiting can be limited to retching, without aspiration and recurrent pneumonia. Some of the retching, however, can be severe, and in one of our patients, a Mallory-Weiss tear occurred, even after a fundoplication. Two and a half years ago, in a combined hospital study in the United States, it was found that nine patients with gastrostomy alone fared about as well as the 12 patients in that series that had fundoplication and pyloroplasty, although we tend to favor the latter combination of pyloroplasty and fundoplication as being a more definitive procedure. It is imperative to construct the fundoplication very loosely, since esophageal dysmotility is very common in these children. If one makes the wrap too tight, one is likely to compound the problem of swallowing in these patients. I would like to ask the authors if they perform routine gastric emptying studies preoperatively, to determine which
VINOGRAD ET AL
patients need pyloroplasty, or do they now do fundoplication and pyloroplasty routinely? How many of your patients have required prolonged gastrostomy feedings? This was necessary in many of the patients in the US study. L Vinograd (closing): Our current policy is to perform a gastrostomy and Nissen fundoplication if surgery is needed and indicated. Only in those cases that radiologic evaluation of the stomach shows pylorospasm or delayed gastric emptying we will add also pyloroplasty. Regarding the second question, our current approach is not to do a gastrostomy alone. We did it only in one of our patients, and this child continues to vomit and suffers from recurrent episodes of aspiration pneumonia. We tend to leave the gastrostomy as long as possible, maybe for 10 or 20 years, as we know that some of the symptoms of familial dysautonomia tends to decrease after puberty, and maybe that by then there will be an indication to remove the gastrostomy.
Jerusalem, Israel 9 Familial dysautonomia (FD) is a rare incurable genetic disorder w i t h multisystem involvement. Most of its clinical manifestations are related to disorders of the autonomic nervous system. The disease is associated w i t h specific disturbances of the upper gastrointestinal tract: pharyngoesophageal dyskinesia, gastroesophageal reflux, and prolonged gastric emptying. About 40% of the dysautonomic children manifest repeat vomiting crises. In view of the extensive gastrointestinal symptomatology, children with FD are prone to repeated aspiration pneumonia and chronic respiratory failure, while inadequate calory and fluid intake may lead to a chronic state of hypovolemia and severe failure to thrive. Control of vomiting, prevention of aspiration due to abnormal swallowing, and the assurance of adequate calory intake are three major objectives in the treatment of the dysautonomic child. Medical treatment of the gastrointestinal disorders using different drugs has had limited success. This study reviews the surgical experience in ten children with FD. The type of the procedure used was determined by the severity of the upper GI disturbances. Nine children underwent gastroesophageal Nissen fundoplication and gastrostomy. In seven of them, a pyloroplasty was added. Gastrostomy alone was done in one patient only. Postoperative complications included transient dysphagia in four patients, gastric dilatation in four patients, and dumping syndrome in one. There has been no incidence of immediate postoperative death, One child died 6 months after operation from severe and irreversible respiratory failure. Following operation, the patients still suffered f r o m dysautonomic crises but these were not associated with vomiting, Pneumonia was eliminated in four children and in five, the incidence of pneumonia was reduced significantly. In s e v e n children, a consistent weight gain was achieved after a short period of adaptibUity. The surgical procedure does not eliminate the dysautonomic crises, yet it does change the quality of life and by reducing the incidence of pneumonia it should have a major effect on the life span in FD patients. 9 1985 by Grune & Stratton, Inc. I N D E X W O R D S : Familial dysautonomia; fundoplication; gastroesophageal reflux.
~AMILIAL D Y S A U T O N O M I A (FD) is a rare incurable genetic disorder with multisystem involvement. The most striking manifestations appear
F
From the Departments of Pediatric Surgery, Anesthesia, and Pediatrics, Hadassah University Hospital, Mount-Scopus, Jerusalem. Presented before the 16th Annual Meeting of the American Pediatric Surgical Association, Kohala Coast, Hawaii, May 1-4, 1985. Address reprint requests to Itzhak Vinograd, MD, Pediatric Surgery Department, Hadassah University Hospital, MountScopus, 91240 Jerusalem, Israel. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2006-0012503.00/0 632
to be disorders of the autonomic system, such as diminished lacrimation, hyperhydrosis, labile blood pressure, derangement of temperature control, and relative insensitivity to pain. Other prominent features are emotional instability and morning nausea) The disease is associated with specific disturbances of the upper gastrointestinal tract; pharngoesophageal dyskinesia, 1abnormal esophageal motility,2 decreased lower esophageal sphincter pressure, 2 abnormal motility of the antrum? and pylorospasm. 2 These result in aspiration of oral feeding and gastroesophageal reflux that is aggravated by prolonged gastric emptying. In addition, about 40% of the dysautonomic children manifest vomiting crises4: repeated, often cyclical vomiting, occurs without any well-understood cause. The typical attack lasts 24 to 72 hours with retching and vomiting as often as every 15 to 20 minutes. The attacks are associated with high blood pressure, perspiration, and red blotching of the skin. In view of the extensive gastrointestinal symptomatology, children with FD are prone to repeated aspiration pneumonia. Inadequate calory and fluid intake may lead to a severe failure to thrive and to a chronic state of hypovolemia. In recent prospective survival study in FD patients, 5 pulmonary complications were the most frequent cause of death. Medical treatment of the gastrointestinal disorders had limited S u c c e s s . 6 Control of vomiting and its life-threatening complications, prevention of aspiration of oral feeding, and adequate calory intake are three critical aims in the treatment of the dysautonomic child. Surgical procedures, such as fundoplication, prevent vomiting; pyloroplasty enables adequate gastric emptying, while gastrostomy may be used for long-term feeding when patients are unable to swallow. Although FD was described as early as 1949, 7 the first attempt of surgical treatment was described in 1982 by Vinograd et al. 8 In the same year, Axelrod et al 9 reported the results of surgical treatment in a larger group of patients. In spite of the extensive information about the clinical manifestations and the experience with medical treatment in FD, there is hardly any data concerning the surgical treatment of this disease. This study reviews our recent experience with the Surgical approach in ten patients with FD. MATERIALS A N D METHODS Ten children with FD who were operated upon in the Pediatric Surgery Service at the Hadassah University Hospital, MountScopus, were evaluated and followed up. The diagnosis of FD was
Journal of Pediatric Surgery. Vo120, No 6 (December), 1985: pp 632-636
SURGICAL MANAGEMENT
OF C H I L D R E N W I T H FD
633
confirmed in all the patients by the distinctive clinical signs of the disease, the absence of flare following intradermal injection of histamine, ~~ absence of fungiform papillae on the tongue, ~ and miosis following instillation of methacholine into the conjunctiva. 12 Preoperatively, all the patients underwent clinical and nutritional assessment. They had radiologic evaluation of the pharyngoesophageal coordination and esophageal and gastric motility studies. Twelve-hour pH monitoring and a milk scan were performed and pulmonary function tests when indicated. The type of the surgical procedure was decided upon by the following criteria: (1) Nissen fundoplication was done for gastroesophageal reflux or cyclic vomiting. (2) Pyloroplasty was performed in patients with pylorospasm or antral dysmotility. (3) Gastrostomy was done for pharyngoesophageal dyskinesia and/or poor nutritional state. Preoperative preparation included intensive pulmonary physiotherapy and deep suction. The performance of a tracheostomy, one week before operation, was considered in children with severe bronchiectasis and poor pulmonary function tests. Broad spectrum antibiotics and cimetidine were given routinely before operation. All the patients received 10 to 20 mL/kg of fresh-frozen plasma on the evening before operation. This was repeated before the induction of anesthesia together with Ringer's lactate solution (5 mL/kg). Premedication consisted of sedation alone (IV Diazepam). Anesthesia was induced and maintained by using the "moderate dose fentanyl" anesthetic technique. ~3At the end of the surgical procedure, residual muscle relaxants and fentanyl-induced respiratory depression were not reversed. All the patients were ventilated until spontaneous ventilation was adequate to permit extubation. When enteral feeding was resumed, the patients were instructed to avoid fluids by mouth and to restrict oral feeding to solids. Fluids were taken through the gastrostomy tube. Whenever the calory intake by mouth was inadequate, it was supplemented by gastrostorey feeding. Follow-up was done regularly. Complete clinical evaluation, nutritional assessment, and postoperative radiologic examinations of the GI tract were carried out.
RESULTS
Ten dysautonomic patients were operated upon during the years 1978 to 1984. There were five males and five females. The mean age at the time of the initial diagnosis of FD was 4.2 years (range, 6 months to 5 years). The mean age at the time of operation was 7.7 years. The youngest patient at the time of operation
was 1.5 years old. Pertinent preoperative clinical findings of major significance are listed in Table 1. Autonomic system disorders were frequent: unstable blood pressure (8 patients), inadequate temperature regulation (5 patients), repeated episodes of breathholding (6 patients), and abnormal EEG in 6 patients, three of whom had overt seizures. Cyclic vomiting crises occurred in 7 patients, two of whom had hematemesis severe enough to require blood transfusions. Moderate to severe scoliosis was found in nine patients. Eight of the patients were in poor nutritional status and in marked growth retardation with both weight and height percentiles of less than 5% before operation. Nine patients had recurrent pneumonia before operation. In seven, the incidence of pneumonia was three or more per six months. The results of the preoperative gastrointestinal assessment and the operative procedures that were performed in each case are summarized in Table 2. Cineesophagograms studies showed objective confirmation of pharyngeoesophageal dyskinesia with aspiration during swallowing in nine patients. The cineesophagograms with the pH monitoring and milk scan confirmed gastroesophageal reflux in nine patients. Delayed gastric emptying was diagnosed in seven patients. In five patients, the radiologic contrast studies showed functional gastric outlet obstruction (pylorospasm). In two patients, the gastric antrum was "funnel shape" and failed to show any evidence of contraction during more than 10 minutes of intermittent fluoroscopic observation. Barium moved by gravity through the pylorus into the duodenum without any evidence of anatomic obstruction. These two pateints were diagnosed as having antral dysmotility. The patients were assigned the following procedures according to the preoperative evaluation: One patient with severe chronic lung disease from repeated aspiraTable 2. P r e o p e r a t i v e Gastrointestinal A s s e s s m e n t and O p e r a t i v e Procedures
Table 1. P r e o p e r a t i v e Clinical Findings in T e n FD P a t i e n t s Nutritional Status
(percentile)
Age at Patient
Sex
Operation
Wt
Ht
GI assessment
Clinicalsymptoms Cyclic Vomiting
Pneumonia*
Patient
PE Dyskinesia
GER
SR
+
+
Operative Procedures
Pylorospasm
Antral Dysmotility
G
F
P
+
--
+
+
+
SR
F
3
<
5%
< 5%
+
--
SM
+
+
+
--
+
§
+
SM
M
7
<
5%
< 5%
+
+ +
SP
--
+
+
--
+
+
+
SP
M
12
<
5%
< 5%
+B
+
KT
+
--
--
--
+
KT
F
1.5
<
5%
< 5%
--
+
DD
+
+
--
--
+
+
--
DD
M
8
50%
< 5%
--
+ +
GZ
+
+
+
--
+
+
+
GZ
M
10
<
5%
<5%
+B
++
KA
+
+
--
+
+
+
+
KA
F
6.5
<
5%
< 5%
+
++
BN
+
+
--
+
+
+
+
BN
M
5
50%
< 5%
+
+ +
SH
+
+
+
--
+
+
+
SH
M
17
<
5%
<5%
+
++
KN
+
+
+
--
+
+
+
KN
F
8
<
5%
< 5%
--
+ +
*+
= 1 t o 2 per 6 too; + + = 3 or m o r e per 6 m o ; + B
associated w i t h severe bleeding.
~ vomiting
A b b r e v i a t i o n s : PE dyskinesia, p h a r y n g e o e s o p h a g e a l dyskinesia; GER, g a s t r o e s o p h a g e a l reflux; G, g a s t r o s t o m y ; plesty.
F, fundoplication;
P, p y l o r o -
634
tion pneumonia underwent a tracheostomy one week before the surgical procedure. Nine patients underwent a Nissen fundoplication and Stamm's gastrostomy. Seven patients with either antral dysmotility or pylorospasm and one patients with neither also had pyloroplasty. Gastrostomy alone was done in one patient. In all ten patients, the operative period was uneventful. Changes in blood pressure and central venous pressure were infrequent and tended to correlate with alterations in heart rate. These changes were responsive to adjustment in the rate of fluid administration. There was no need for exogenous cathecholamines in any of the patients. Postoperatively, the patients were in full consciousness within four to eight hours. Extubation was performed whenever spontaneous ventilation was found to be adequate and usually within six to 14 hours postoperatively. One patient required reintubation for severe bronchospasm that responded to a heavy dose of steroids and bronchodilators. There was no immediate postoperative death. The follow-up period in these children has ranged from 6 months to 7 years (mean, 20.7 months). In seven children, a persistent weight gain was noted after a short adaptation period of 1 to 2 months. Weight gain was marked in four children who adhered to gastrostomy feedings regimen. The occurrence of pneumonia was reduced significantly in all nine patients who had aspiration pneumonia before operation. In four of them, pneumonia was totally eliminated. However, two children with severe bonchiectatic lung disease continued to have occasional episodes of pneumonia. Of these, the patient who had severe and irreversible lung disease and therefore underwent tracheostomy, died six months after the fundoplication. He died because of respiratory failure three months after the removal of the tracheostomy. Two other patients, who repeatedly attempted drinking against advice, also had episodes of pneumonia. In one, the pneumonia recurred shortly after the removal of gastrostomy. The gastrostomy was reluctantly removed due to excessive leakage of gastric fluid and the family objected to its reintroduction. The patient who had only a gastrostomy done, still suffered from pneumonia but at a reduced rate. Symptoms of overt cyclic vomiting as part of the dysautonomic crises were present in seven children before operation. Following operation, the crises continued but were not associated with vomiting. The patient who had placement of a gastrostomy only, developed vomiting attacks six months after operation. In two patients, breath-holding spells stopped following operation. Postoperative complications included transient dys-
VINOGRAD ET AL
phagia in five patients and "gas bloat" in four. The last was relieved by opening the gastrostomy tube. One patient developed postoperatively dumping syndrome that was treated by the reduction of carbohydrates in his diet. Excessive granulation tissue around the gastrostomy tube was a problem in three patients. A repeated UGI series was performed postoperatively in all patients. Gastric reflux was found only in the one patient in whom a gastrostomy alone was performed. In one patient, the fundoplication and the gastric fundus herniated through the hiatus into the lower mediastinum without affecting the competence of the antireflux operation. DISCUSSION
Familial dysautonomia (FD) or Riley-Day syndrome was originally described in 1949. 7 Since then, experience in treatment of FD has broadened considerably. Major advances in the understanding of the pathophysiology and the clinical features brought about a more rational and active approach to the treatment of the disease. However, mortality is still high in FD, particularly during the early years of life. 1 Acute and chronic pulmonary infections, secondary to repeated aspirations, are the most common cause of death, while delayed or inadequate management of vomiting crises and dehydration may have fatal consequences. Surgical treatment that is aimed toward prevention of vomiting, prevention of aspiration due to abnormal swallowing, and toward enabling adequate calory intake may prolong life and improve its quality. There are about 250 patients known to suffer from FD as reported by Axelrod et alS; 66% of them are younger than 20 years. To date, according to the published series, gastrointestinal operation was performed in only 33 patients, g'9 Gastrostomy alone was done in 13 and gastroesophageal fundoplication in 20. Although the results of the surgical treatment in this disease are encouraging, no distinct guidelines have yet been established for the rational approach to the gastrointestinal manifestations in FD. Various types of surgical procedures have been tried in order to prevent vomiting secondary to GER. None had complete success. However, the Nissen fundoplication has proved to be effective and with a relatively low complication rate. 14 In the typically morningnauseated FD child and in FD infants having difficulty in sucking and swallowing, gastrostomy alone was used in order to ensure adequate nutrition.9 The dysautonomic child is able to sense the position of soft food in his mouth but has greater difficulty in doing so in the case of liquids. Gastrostomy feeding can be used until the child learns how to swallow. Meanwhile, solid food should be given orally, since normal speech is related to
SURGICAL MANAGEMENT OF CHILDREN WITH FD
635
normal feeding patterns. The same groups of muscles are involved in both. The combination of pharyngoesophageal dyskinesia and gastroesophageal reflux is very common in FD patients. In the present group, 90% of the children had that combination. It appears that unless megaesophagus, described sometimes in FD patients but not found in our patients, is present, fudoplication and gastrostomy would be the operation of choice. The only patient in this series who underwent gastrostomy alone still suffers from recurrent vomiting and aspiration pneumonia though at a lesser frequency. In the presence of prolonged gastric emptying, a pyloroplasty is also indicated. Timing is of crucial importance in the surgical management of the FD child. Bronchiectasis and pulmonary disease were present in two of our patients. One of them died six months after operation and the other continued to suffer from recurrent pneumonia but to a lesser extent. Recent reviews, in non-FD population, have elaborated on the role of gastroesophageal reflux in the production of chronic pulmonary diseases and have demonstrated that gastroesophageal fundoplication can be of benefit in the treatment of refractory or recurrent pneumonia, failure to thrive, and intractable vomiting. ~4'~5 Cyclic vomiting tends to decrease after puberty in some of the dysautonomic children. But in anticipation that a major part of the pulmonary dam-
age occurs during infancy and early childhood, prevention by an early surgical procedure seems to be rational. In addition, frequent milk aspirations may cause sensitization with mucus production and wheezing on subsequent exposure. General anesthesia was considered to be associated with a considerable risk to the FD patient. However, with the increased understanding of the pathophysiology of dysautonomia and the growing experience with anesthesia in this disease, operations can be performed as indicated regardless of the patient's age. It has been suggested that if swallowing dysfunction coexists with gastroesophageal reflux, then the fundoplication results may not be as favorable. ~4 Evidence for disorders in esophageal motility and pharyngoesophageal dyskinesia exists in many of the dysautonomic patients. Yet, in the present series, the dysphagia was transient and faded with time. The surgical procedure does not eliminate the dysautonomic crises, yet it does change the quality of life and by reducing the incidence of pneumonia it should have a major effect on the life span of FD patients. This experience substantiates the efficacy and relative safety of early surgical treatment, including gastroesophageal fundoplication, gastrostomy, and pyloroplasty in patients with familial dysautonomia.
REFERENCES 1. Axelrod FB, Nachtigal R, Dancis J: Familial dysautonomia: Diagnosis, pathogenesis and management, in Schulman I (ed): Advances in Pediatrics (Vol 21). Chicago, Year Book Medical, 1974, pp 75-96 2. Linde LM, Westover JL: Esophageal and gastric abnormalities in dysautonomia. Pediatrics 29:303-306, 1962 3. Mulvihill S J, Fonkalsrud EW: Pyloroplasty in infancy and childhood. J Pediatr Surg 18:930-936, 1983 4. Riley CM: Familial dysautonomia, in Levine SZ (ed): Advances in Pediatrics (Vol 9). Chicago, Year Book Medical, 1957, pp 157-190 5. Axelrod FB, Abularrage J J: Familial dysautonomia: A prospective study of survival. J Pediatr 101:234-236, 1982 6. Axelrod FB, Branom N, Becker M, et al: Treatment of familial dysautonomia with bethanechol (urecholine). J Pediatr 81:573-578, 1971 7. Riley CM, Day RL, Greeley DMcL, et al: Central autonomic dysfunction with defective lacrimation. Pediatrics 3:468-476, 1949 8. Vinograd I, Lernau OZ, Frand M, et al: Fundoplication and
pyloroplasty--a surgical treatment for intractable "cyclic vomiting" in familial dysautonomia. J Pediatr Surg 17:80-81, 1982 9. Axelrod FB, Schneider KM, Ament ME, et al: Gastroesophageal fundoplication and gastrostomy in familial dysautonomia. Ann Surg 195:253-258, 1982 10. Smith AA, Dancis J: Response to intradermal histamine in familial dysautonomia--a diagnostic sign. J Pediatr 63:889-894, 1963 11. Smith AA, Farhman A, Dancis J: Tongue in familial dysautonomia, a diagnostic sign. Am J Dis Child 110:152-154, 1965 12. Smith AA, Dancis J, Breinin G: Ocular responses to autonomic drugs in familial dysautonomia. Invest Ophtalmol 4:358-361, 1965 13. Beilin B, Maayan Ch, Vatashsky E, et al: Fentanyl anesthesia in familial dysautonomia. Anesth Analg 64:72-76, 1985 14. Leape LL, Ramenofsky ML: Surgical treatment of gastroesophageal reflux in children. Results in Nissen's fundoplication in 100 children. Am J Dis Child 134:935-938, 1980 15. Jolley SG, Herbst J J, Johnson DG, et al: Surgery in children with gastroesophageal reflux and respiratory symptoms. J Pediatr 96:194-198, 1980
Discussion Eric Fonkalsrud (Los Angeles): Dr Vinograd and his colleagues from Jerusalem have compiled the largest single hospital experience in the surgical manage-
ment of these unfortunate children with familial dysautonomia, and are to be congratulated on their excellent results. Neither gastrostomy nor fundoplica-
636
tion cures the dysautonomic crises, as the authors have pointed out; and drug therapy is still required for the systemic manifestations of the disease. However, the vomiting can be limited to retching, without aspiration and recurrent pneumonia. Some of the retching, however, can be severe, and in one of our patients, a Mallory-Weiss tear occurred, even after a fundoplication. Two and a half years ago, in a combined hospital study in the United States, it was found that nine patients with gastrostomy alone fared about as well as the 12 patients in that series that had fundoplication and pyloroplasty, although we tend to favor the latter combination of pyloroplasty and fundoplication as being a more definitive procedure. It is imperative to construct the fundoplication very loosely, since esophageal dysmotility is very common in these children. If one makes the wrap too tight, one is likely to compound the problem of swallowing in these patients. I would like to ask the authors if they perform routine gastric emptying studies preoperatively, to determine which
VINOGRAD ET AL
patients need pyloroplasty, or do they now do fundoplication and pyloroplasty routinely? How many of your patients have required prolonged gastrostomy feedings? This was necessary in many of the patients in the US study. L Vinograd (closing): Our current policy is to perform a gastrostomy and Nissen fundoplication if surgery is needed and indicated. Only in those cases that radiologic evaluation of the stomach shows pylorospasm or delayed gastric emptying we will add also pyloroplasty. Regarding the second question, our current approach is not to do a gastrostomy alone. We did it only in one of our patients, and this child continues to vomit and suffers from recurrent episodes of aspiration pneumonia. We tend to leave the gastrostomy as long as possible, maybe for 10 or 20 years, as we know that some of the symptoms of familial dysautonomia tends to decrease after puberty, and maybe that by then there will be an indication to remove the gastrostomy.