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Feeding problems and malnutrition in spinal muscular atrophy type II
Neuromuscular Disorders 18 (2008) 389–393 www.elsevier.com/locate/nmd
Feeding problems and malnutrition in spinal muscular atrophy type II Sonia Messina a,b, Marika Pane a, Paola De Rose a, Isabella Vasta a, Domenica Sorleti c, Annie Aloysius d, Federico Sciarra e, Fortunato Mangiola e, Maria Kinali d, Enrico Bertini f, Eugenio Mercuri a,d,* a Department of Child Neurology, Policlinico Gemelli, Largo Gemelli, Rome, Italy Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy c Department of Paediatrics, University of Messina, Messina, Italy d Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK e Unione Italiana Lotta Distrofia Muscolare, Rome, Italy f Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu` Hospital, Rome, Italy b
Received 16 November 2007; received in revised form 12 February 2008; accepted 29 February 2008
Abstract The aim of the study was to conduct a survey using a dedicated questionnaire to assess feeding difficulties and weight gain in a population of 122 Spinal Muscular Atrophy (SMA) type II patients, aged between 1 and 47 years. All the answers were entered in a database and were analysed subdividing the cohort into age groups (1–5, 6–10, 11–14, 15–19, 20–29, and 30–50 years). Six out of our 122 patients (5%), all younger than 11 years, had weights more than 2SD above the median for age matched controls, whilst 45 (37%) had weights less than 2SD below the median. Chewing difficulties were reported in 34 of the 122 patients (28%) and limitation in the ability to open the mouth in 36 (30%) and both were increasingly more frequent with age. Swallowing difficulties were reported in 30 patients (25%). The results of our survey suggest that a number of patients with SMA type II have limited jaw opening, and chewing and swallowing difficulties. Our findings raise a few issues concerning standards of care that should be implemented in the monitoring and management of feeding difficulties and weight gain. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Feeding difficulties; Spinal muscular atrophy; Swallowing; Dysphagia
1. Introduction Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting the spinal cord motoneurons [1]. The classification of SMA is based on the maximal motor function achieved [2–4]. Children with the intermediate form (SMA type II) are able to sit but never achieve the ability to walk independently. It has been recently reported that in these patients the severity of functional impairment
* Corresponding author. Address: Department of Child Neurology, Policlinico Gemelli, Largo Gemelli 00168, Rome, Italy. Tel.: +39 06 30155340; fax: +39 06 30154363. E-mail address: [email protected] (E. Mercuri).
0960-8966/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2008.02.008
inversely correlates with the SMN2 copy number that is usually 2 or 3 [5]. Progressive respiratory involvement and scoliosis are frequent complications [1]. Feeding problems are frequently reported by patients with SMA type II, but there are only few studies focusing on this aspect [6–8]. In a survey on swallowing problems in neuromuscular disorders approximately one-third of the patients with SMA had feeding-related issues, with a predominance of problems related to the pre-oral phase, such as limited mouth opening and difficulties in getting food to the mouth for self-feeding [6]. It has also been reported that reduced bite force and increased fatigue of masticatory muscles can cause an increase of in length of mealtimes [9]. Chewing difficulties may also be related to craniofacial abnor-
390
S. Messina et al. / Neuromuscular Disorders 18 (2008) 389–393
malities including dental malocclusion, anterior open bite and flaring of the upper incisors associated with masticatory muscle weakness [10]. Poor head control may preclude compensatory postures used to enhance the safety of swallowing [10]. Bulbar involvement resulting in pharyngeal swallowing problems is more frequent in SMA type I [1,11,12], but has also been reported in SMA type II [6]. As a consequence of the swallowing problems, patients may be at risk of aspiration of food or liquids and consequent aspiration pneumonia. Most of the previous studies only involved small cohorts of patients with different types of SMA, and the data may have been influenced by a bias due to the inclusion of patients with SMA type I. No systematic study has been performed to assess feeding problems in patients with SMA type II. Moreover, although excessive weight gain or more often growth failure are known to be frequent in SMA patients [1,8], this aspect has not been systematically investigated. The aim of this study was to conduct a survey using a questionnaire on feeding difficulties and anthropometric data in a large cohort of SMA type II patients with ages ranging between 1.1 and 47.0 years and to correlate these findings with other variables such as age, use of ventilatory support and other aspects of clinical management. 2. Patients and methods The survey was conducted from October 2006 to May 2007. All participants had a genetically confirmed diagnosis of SMA with homozygous absence of SMN1 gene. Patients were classified as having SMA type II because they were able to sit independently but they never achieved the ability to walk unsupported [2–4]. Patients were recruited from those attending the Paediatric Neurology Unit of the Catholic University in Rome or a centre for diagnosis and rehabilitation of muscle disorders (Unione Italiana Lotta Distrofia Muscolare) of Rome or were referred by a family association (Famiglie SMA, Italy).
One hundred and twenty-five patients/families were first contacted by mail with a letter explaining the study and asking permission for their participation. Patients were subsequently contacted by phone by a paediatric neurologist (PD) asking the families if they were happy to participate and if the time of the day was convenient for a short interview. All but three patients consented to participate in the study. The interview was performed using a semi-structured questionnaire, answered by the patients or the parents of the younger children wherever felt appropriate. All answers were recorded at the time of the interview on a dedicated proforma and subsequently transferred to a database. The questionnaire was designed by a consensus of neurologists, paediatricians, and speech therapists and has already been used in a cohort of patients with Duchenne muscular dystrophy [13]. The questionnaire includes simple specific questions on feeding abilities, including duration to complete a meal and feeding difficulties, subdivided according to whether these were related to the extrabuccal (opening mouth), anterior (keeping food in mouth, chewing) or posterior (choking, repeat attempt to swallow, food aspiration) phases of chewing and swallowing. Dietary modifications such as changes in the consistency or quantity of administered food, medications or supplements intake were also recorded. We also documented gastrointestinal dysfunction, particularly the presence of gastroesophageal reflux (GER), meteorism, constipation and abdominal pain. We collected data on ventilatory support and gastrostomy placement. Patients were also asked to report the last weight measurement. This, measured in kilograms, was converted in Z-scores calculated according to CDC’s (Center for Disease Control) age and sex specific growth charts [14]. 3. Results We analysed the questionnaires of all 122 (F/M, 54/68) SMA type II patients who consented to take part in the survey. Their ages ranged between 1.1 and 47.0 years (median: 11.9 years). The cohort was subsequently subdivided into 6 groups according to age (Table 1).
Table 1 Feeding difficulties, gastrostomy, and episodes of aspiration pneumonia
Age (years) Number Meal time in minutes (mean (±SD)) Difficulty opening mouth Difficulty chewing Choking with liquids only Choking with semisolids Choking with solids only Choking on both liquids and solids Swallowing not choking Total patients with choking and/or swallowing difficulties Dietary modifications Gastrostomy Aspiration pneumonia SD, standard deviation.
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
1–5 25 28(±15.0) 2 (8%) 2 (8%) 0 0 2 (8%) 0 0 2 (8%) 2 (8%) 0 2 (8%)
6–10 30 30 (±16.5) 7 (23%) 7 (23%) 1 (3.3%) 0 2 (6.6%) 2 (6.6%) 2 (6.6%) 7 (23%) 8 (26.6%) 1 (3.3%) 1 (3.3%)
11–14 19 28 (±13.56) 4 (21%) 7 (36.8%) 0 0 1 (5.2%) 1 (5.2%) 0 2(10.5%) 4 (21%) 1 (5.2%) 0
15–19 21 28 (±16.0) 6 (28%) 4 (19%) 0 0 3 (14.2%) 0 4 (19%) 7 (33.3%) 4 (19%) 0 1 (4.7%)
20–29 13 31 (±12.1) 6 (46%) 7 (53.8%) 0 0 5 (38.4%) 1 (7.6%) 0 6 (46%) 4 (30.7%) 0 0
30–50 14 28 (±8.9) 11 (78%) 7 (50%) 1 (7.1%) 0 1 (7.1%) 3 (21.4%) 1 (7.1%) 6 (42.8%) 5 (35.7%) 1 (7.1%) 0
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choking episode but complained of swallowing difficulties. Dietary changes, mainly consisting in cutting food in smaller pieces or preference for smooth food, were recorded in 27 patients (22%) and were also more frequent in patients older than 20 years (groups 5 and 6). Duration of meal time did not increase with age. Only four patients (3%) reported episodes of proven aspiration pneumonias. There was no difference between sexes. Details of feeding difficulties are shown in Table 1. 3.3. Gastrointestinal symptoms
Fig. 1. Body weight distribution according to age. G, group.
3.1. Weight
Five of our 122 patients (4%) had been diagnosed with GER and were on medical treatment. Another 18 patients (15%) complained of recurrent abdominal pain and 9 (7%) of other symptoms that could be possibly related to GER (Table 2). 3.4. Ventilatory support
Fig. 1 shows details of the weight in the cohort in relation to age. Compared to age and sex matched controls from standardised weight charts [14], 45 out of our 122 patients (37%) showed a weight below 2SD with some patients falling as low as below 9SD. Fourteen out of the 27 patients above the age of 20 (groups 5 and 6) (50%) had weights below 2SD. Only six out of 122 patients (5%) showed a weight above 2SD and these were all below the age of 10 (groups 1 and 2). There was no difference between sexes. 3.2. Feeding difficulties Limited mouth opening and chewing difficulties were reported in 36 and in 34 out of 122 patients, respectively, (30% and 28%) and were more frequent in patients older than 20 years (groups 5 and 6). Choking episodes were reported in 23 patients (19%) and were more frequent in patients older than 20 years (groups 5 and 6). Seven patients (6%) had choking episodes with both solids and liquids, 14 (11%) with solids only and two (2%) with liquids only. Another seven patients (6%) did not report any
Four patients (3%) had tracheostomy at mean age of 26 years (range 14–38 years) (1 in group 3; 1 in group 5 and 2 in group 6) and 15 (12%) had non-invasive ventilation (NIV) at a mean age of 11 years (range 5–26 years) (Table 2). 3.5. Gastrostomy Gastrostomy was placed in three patients (2%) at mean age of 20 years (range 10–40 years) (1 in group 2; 1 in group 3 and 1 in group 6). Of those one patient did not require any ventilator support, one was on NIV and one had tracheostomy. All patients continue to regularly feed by mouth (Table 1). 3.6. Ventilatory support and feeding difficulties Feeding difficulties were present in 15 of the 103 patients (14%) without ventilatory support, in six of the 15 patients (40%) on NIV and in two of the four patients (50%) having tracheostomy.
Table 2 Gastrointestinal symptoms and ventilatory support
Age (years) Number Diagnosed GER Symptoms of GER Constipation Constipation treatment Meteorism Abdominal pain Tracheostomy NIV
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
1–5 25 0 1 (4%) 15 (60%) 14 (56%) 3 (12%) 2 (8%) 0 3 (12%)
6–10 30 0 4 (13.3%) 12 (40%) 9 (30%) 3 (10%) 6 (20%) 0 4 (13.3%)
11–14 19 2 (10.5%) 1 (5.2%) 9 (47%) 9 (47%) 1 (5.2%) 3 (15.7%) 1 (5.2%) 3 (15.7%)
15–19 21 1 (4.7%) 1 (4.7%) 9 (42.8%) 9 (42.8%) 2 (9.5%) 3 (14.2%) 0 2 (9.5%)
20–29 13 0 2 (15.3%) 4 (30.7%) 3 (23.0%) 3 (23.0%) 3 (23.0%) 1 (7.6%) 2 (15.3%)
30–50 14 2 (14.2%) 0 4 (28.5%) 4 (28.5%) 5 (35.7%) 1 (7.1%) 2 (14.2%) 1 (7.1%)
GER, gastroesophageal reflux; NIV, non-invasive ventilation.
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100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
Tracheostomy (N=3) >2SD
NIV (N=15)
No ventilatory support (N=103)
WITHIN 2SD
<2SD
Fig. 2. Ventilatory support and weight. NIV, non-invasive ventilation.
3.7. Ventilatory support and weight Fig. 2 shows the percentage of weight within 2SD, above and below 2SD in patients with tracheostomy, on nocturnal NIV and in those with no ventilatory support. 4. Discussion The aim of our study was to conduct a survey to evaluate feeding problems in a population of SMA type II patients with age between 1 and 47 years. In our cohort the most frequently reported problems were limited mouth opening and difficulties in chewing. These were present in all age groups, but were more frequent in patients older than 20 years. Predominant difficulties in the pre-oral and oral phases of deglutition have already been reported in SMA [6,9,10], but the results cannot be easily compared as previous studies included patients with different types of SMA. Furthermore, most of the previous studies were performed at a time when genetic confirmation of SMN1 deletion was not available. Our study has the advantage that our population is better characterised and more homogeneous as all our patients had a genetically confirmed diagnosis and onset, progression of the disease and maximal functional ability achieved (sitting unsupported) that were always consistent with the diagnosis of SMA type II. Swallowing difficulties were overall present in 25% of patients and reported at all ages but they were also more common in patients older than 20 years. In most of these patients the difficulties consisted in documented recurrent choking episodes with solids or with both solids and liquids. Of note 6% of our patients reported swallowing difficulties and fear rather than true occurrence of choking episodes. Because of this, most of these patients have introduced dietary modifications, such as cutting food in small pieces or preference for pureed food in order to facilitate chewing and reduce the risk of choking. In our study only four patients reported well documented aspiration pneumonias. Several other patients
had a recurrence of chest infections that were not always preceded by upper respiratory tracts infections. The results of chest X-rays however were not available to us as these acute ‘‘silent” episodes were usually managed at local hospitals, and we cannot therefore be certain of the true occurrence of signs of food aspiration. Aspiration has been reported to be frequent (68–70%) in children with severe neurological disability [15,16], but is much less frequent (approximately 6%) in patients with Duchenne Muscular Dystrophy [13]. Recent International Coordination Committee (ICC) guidelines on standards of care in SMA (ICC) have suggested that this aspect should be always examined in SMA type I, while in SMA type II patients a decision should be made according to clinical signs [17]. We were also interested to collect data regarding body weight to evaluate suboptimal and excessive weight gain at different age groups. Although we were aware that data on weight collected with a phone interview had several limitations, including the lack of consistent measurements and of other useful indexes often not routinely provided, we felt that the data could still be useful as a rough indicator of the number of patients grossly undernourished or overweight. The other limitation is that there are no normative data for patients with SMA or other neuromuscular disorders and that the measures were therefore analysed using standards charts that do not take into account muscle wasting. Even with all these limitations we found interesting that only six out of our 122 patients (5%) had a weight above 2SD for age and they were all below 10 years. Poor weight gain in contrast was more frequent, with 37% of patients having a weight below 2SD compared to age and sex matched controls from standardised weight charts [14] with approximately half of them falling below 4SD. These findings appear to be relevant even considering the limitations of the study. Although this was more frequent in patients older than 20 years (55% of patients between 21 and 47 years), it was also present in a significant number of younger patients. Not surprisingly patients with failure to thrive reported more often the association of two (22% of patients) or three (20%) problems among limited mouth opening, chewing and swallowing difficulties, than patients with weight within 2SD (9% and 2%, respectively). However the extent to which each of these factors may have contributed cannot be easily ascertained from this type of survey. As not all of these patients were followed in tertiary care centers, we also tried to examine whether the poor weight gain was associated with known possible causative factors such as nocturnal hypoventilation. On interview the great majority of our patients however reported to have routine respiratory assessments with spirometry and overnight sleep studies and there were less patients with poor weight gain in the non-ventilated group than in the groups treated with NIV or tracheostomy. We were surprised that even if poor weight gain was often associated with swallowing difficulties, only a few patients, all followed in tertiary care centers, had been
S. Messina et al. / Neuromuscular Disorders 18 (2008) 389–393
extensively investigated with videofluoroscopy swallow studies (VFSS) or had their weight carefully monitored by dieticians or were started on dietary supplements. Only a small minority (three patients) had gastrostomy. It is even more surprising that only five patients were treated for GER, reported as a common problem in patients with SMA [17]. On direct questioning approximately 25% of patients also complained of recurrent episodes of abdominal pain, but we were not able to distinguish, on the basis of our questionnaire, a more precise location of pain or its nature. Our results should be interpreted with caution because of the design of the study. Our patients are part of a heterogeneous cohort followed in several centres, and the majority are not followed in tertiary care centers, where care can be coordinated by multidisciplinary teams. Nevertheless our findings raise a few issues about standards of care in SMA type II and suggest some considerations. Poor weight gain appears to be common in our cohort and a systematic evaluation of weight gain should be part of the routine medical examination in order to identify early signs of failure to thrive. More accurate measurements of weight together with other measures of nutritional status such as skinfold thickness should be accurately evaluated for determining comprehensive feeding strategies and recommendations. It is well recognised that malnutrition can be associated with respiratory dysfunction, blunt immunological responses and may lead to an increased risk of chest infections [18,19]. A better management of the nutritional status may thus help to reduce the number of chest infections and of hospital admissions and to improve patients quality of life. Patients should also always be carefully interviewed for symptoms of swallowing difficulties that may require VFSS to objectively assess swallowing. A more systematic approach with chest radiographs at the time of recurrent acute chest infections not necessarily preceded by upper respiratory tract infections could also be useful to document possible ‘‘silent” aspiration pneumonias. It would also be relevant to establish whether abnormal neck postures secondary to scoliosis or scoliosis surgery, could contribute to the swallowing difficulties and suboptimal weight gain in this population. Although from our findings GER does not appear to be frequent, this was not systematically evaluated and this aspect should be more appropriately addressed. Our results also suggest how an integrated multidisciplinary approach is needed in these patients in order to identify feeding difficulties and to optimise their management. At present several treatment options such as dietary modifications, adopting safe swallowing techniques, surgical interventions and enteral feeding are available, but as suggested by a recent Cochrane review on management and therapy for dysphagia in chronic muscle disease [20], systematic randomised studies are needed to establish the
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best treatment options for feeding problems in these patients. Acknowledgements We thank patients and their families and the Families of SMA Association Italy for their kind cooperation. We also thank TREAT-NMD project for the support to S.M. References [1] Dubowitz V. Disorders of the lower motor neuron: the spinal muscular atrophies. In: Dubowitz V, editor. Muscle disorders in childhood. London: Saunders; 1995. p. 325–67. [2] Dubowitz V. Chaos in the classification of SMA: a possible resolution. Neuromuscul Disord 1995;5:3–5. [3] Munsat T, Davies KE. International SMA consortium meeting, 26– 28th June 1992, Bonn, Germany. Neuromuscul Disord 1992;2:423–8. [4] Zerres K, Rudnik-Schonenborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 1995;52:518–23. [5] Tiziano FD, Bertini E, Messina S, et al. The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study. Neuromuscul Disord 2007;17:400–3. [6] Willig TN, Paulus J, Lacau Saint Guily J, Beon C, Navarro J. Swallowing problems in Neuromuscular Disorders. Arch Phys Med Rehabil 1994;75:1175–81. [7] Willig TN, Bach JR, Venance V, Navarro J. Nutritional rehabilitation in neuromuscular disorders. Semin Neurol 1995;15:18–23. [8] Tilton AH, Miller M, Khoshoo V. Nutrition and swallowing in paediatric neuromuscular patients. Semin Pediatr Neurol 1998;5:106–15. [9] Granger MW, Buschang PH, Throckmorton GS, Iannaccone ST. Masticatory muscle function in patients with spinal muscular atrophy. Am J Orthod Dentofacial Orthop 1999;115:697–702. [10] Houston K, Buschang PH, Iannaccone ST, Seale NS. Craniofacial morphology of spinal muscular atrophy. Pediatr Res 1994;36:265–9. [11] Nutman J, Nitzan M, Grunebaum M. Swallowing disturbances in Werdnig–Hoffman disease (in Hebrew). Harefuah 1981;101:301–3. [12] Grunebaum M, Nutman J, Nitzan M. The pharyngo-laryngeal deficit in the acute form of infantile spinal muscular atrophy (Werdnig– Hoffmann disease). Pediatr Radiol 1981;11:67–70. [13] Pane M, Vasta I, Messina S, et al. Feeding problems and weight gain in Duchenne muscular dystrophy. Eur J Paediatr Neurol 2006;10:231–6. [14] Kuczmarski RJ, Ogden CL, Guo SS, et al. CDC growth charts for the United States: methods and development. Vital Health Stat 2002;246:1–190. [15] Griggs GA, Findley LJ, Suratt PM, Esau SA, Wilhoit SC, Rochester DF. Prolonged relaxation rate of inspiratory muscles in patients with sleep apnea. Am Rev Respir Dis 1989;140:706–10. [16] Mirrett PL, Riski JE, Glascott J, Johnson V. Videofluoroscopic assessment of dysphagia in children with severe spastic cerebral palsy. Dysphagia 1994;9:3174–9. [17] Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A. Consensus statement for standard care in spinal muscular atrophy. J Child Neurol 2007;22:1027–49. [18] Cunningham-Rundles S. Effects of nutritional status on immunological function. Am J Clin Nutr 1982;35:1202–10. [19] Aldrich TK. Nutritional factors in the pathogenesis and therapy of respiratory insufficiency in neuromuscular diseases. Monaldi Arch Chest Dis 1993;48:327–30. [20] Hill M, Hughes T, Milford C. Treatment for swallowing difficulties (dysphagia) in chronic muscle disease. Cochrane Database Syst Rev 2004;2:CD004303.
Feeding problems and malnutrition in spinal muscular atrophy type II Sonia Messina a,b, Marika Pane a, Paola De Rose a, Isabella Vasta a, Domenica Sorleti c, Annie Aloysius d, Federico Sciarra e, Fortunato Mangiola e, Maria Kinali d, Enrico Bertini f, Eugenio Mercuri a,d,* a Department of Child Neurology, Policlinico Gemelli, Largo Gemelli, Rome, Italy Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy c Department of Paediatrics, University of Messina, Messina, Italy d Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK e Unione Italiana Lotta Distrofia Muscolare, Rome, Italy f Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu` Hospital, Rome, Italy b
Received 16 November 2007; received in revised form 12 February 2008; accepted 29 February 2008
Abstract The aim of the study was to conduct a survey using a dedicated questionnaire to assess feeding difficulties and weight gain in a population of 122 Spinal Muscular Atrophy (SMA) type II patients, aged between 1 and 47 years. All the answers were entered in a database and were analysed subdividing the cohort into age groups (1–5, 6–10, 11–14, 15–19, 20–29, and 30–50 years). Six out of our 122 patients (5%), all younger than 11 years, had weights more than 2SD above the median for age matched controls, whilst 45 (37%) had weights less than 2SD below the median. Chewing difficulties were reported in 34 of the 122 patients (28%) and limitation in the ability to open the mouth in 36 (30%) and both were increasingly more frequent with age. Swallowing difficulties were reported in 30 patients (25%). The results of our survey suggest that a number of patients with SMA type II have limited jaw opening, and chewing and swallowing difficulties. Our findings raise a few issues concerning standards of care that should be implemented in the monitoring and management of feeding difficulties and weight gain. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Feeding difficulties; Spinal muscular atrophy; Swallowing; Dysphagia
1. Introduction Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting the spinal cord motoneurons [1]. The classification of SMA is based on the maximal motor function achieved [2–4]. Children with the intermediate form (SMA type II) are able to sit but never achieve the ability to walk independently. It has been recently reported that in these patients the severity of functional impairment
* Corresponding author. Address: Department of Child Neurology, Policlinico Gemelli, Largo Gemelli 00168, Rome, Italy. Tel.: +39 06 30155340; fax: +39 06 30154363. E-mail address: [email protected] (E. Mercuri).
0960-8966/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2008.02.008
inversely correlates with the SMN2 copy number that is usually 2 or 3 [5]. Progressive respiratory involvement and scoliosis are frequent complications [1]. Feeding problems are frequently reported by patients with SMA type II, but there are only few studies focusing on this aspect [6–8]. In a survey on swallowing problems in neuromuscular disorders approximately one-third of the patients with SMA had feeding-related issues, with a predominance of problems related to the pre-oral phase, such as limited mouth opening and difficulties in getting food to the mouth for self-feeding [6]. It has also been reported that reduced bite force and increased fatigue of masticatory muscles can cause an increase of in length of mealtimes [9]. Chewing difficulties may also be related to craniofacial abnor-
390
S. Messina et al. / Neuromuscular Disorders 18 (2008) 389–393
malities including dental malocclusion, anterior open bite and flaring of the upper incisors associated with masticatory muscle weakness [10]. Poor head control may preclude compensatory postures used to enhance the safety of swallowing [10]. Bulbar involvement resulting in pharyngeal swallowing problems is more frequent in SMA type I [1,11,12], but has also been reported in SMA type II [6]. As a consequence of the swallowing problems, patients may be at risk of aspiration of food or liquids and consequent aspiration pneumonia. Most of the previous studies only involved small cohorts of patients with different types of SMA, and the data may have been influenced by a bias due to the inclusion of patients with SMA type I. No systematic study has been performed to assess feeding problems in patients with SMA type II. Moreover, although excessive weight gain or more often growth failure are known to be frequent in SMA patients [1,8], this aspect has not been systematically investigated. The aim of this study was to conduct a survey using a questionnaire on feeding difficulties and anthropometric data in a large cohort of SMA type II patients with ages ranging between 1.1 and 47.0 years and to correlate these findings with other variables such as age, use of ventilatory support and other aspects of clinical management. 2. Patients and methods The survey was conducted from October 2006 to May 2007. All participants had a genetically confirmed diagnosis of SMA with homozygous absence of SMN1 gene. Patients were classified as having SMA type II because they were able to sit independently but they never achieved the ability to walk unsupported [2–4]. Patients were recruited from those attending the Paediatric Neurology Unit of the Catholic University in Rome or a centre for diagnosis and rehabilitation of muscle disorders (Unione Italiana Lotta Distrofia Muscolare) of Rome or were referred by a family association (Famiglie SMA, Italy).
One hundred and twenty-five patients/families were first contacted by mail with a letter explaining the study and asking permission for their participation. Patients were subsequently contacted by phone by a paediatric neurologist (PD) asking the families if they were happy to participate and if the time of the day was convenient for a short interview. All but three patients consented to participate in the study. The interview was performed using a semi-structured questionnaire, answered by the patients or the parents of the younger children wherever felt appropriate. All answers were recorded at the time of the interview on a dedicated proforma and subsequently transferred to a database. The questionnaire was designed by a consensus of neurologists, paediatricians, and speech therapists and has already been used in a cohort of patients with Duchenne muscular dystrophy [13]. The questionnaire includes simple specific questions on feeding abilities, including duration to complete a meal and feeding difficulties, subdivided according to whether these were related to the extrabuccal (opening mouth), anterior (keeping food in mouth, chewing) or posterior (choking, repeat attempt to swallow, food aspiration) phases of chewing and swallowing. Dietary modifications such as changes in the consistency or quantity of administered food, medications or supplements intake were also recorded. We also documented gastrointestinal dysfunction, particularly the presence of gastroesophageal reflux (GER), meteorism, constipation and abdominal pain. We collected data on ventilatory support and gastrostomy placement. Patients were also asked to report the last weight measurement. This, measured in kilograms, was converted in Z-scores calculated according to CDC’s (Center for Disease Control) age and sex specific growth charts [14]. 3. Results We analysed the questionnaires of all 122 (F/M, 54/68) SMA type II patients who consented to take part in the survey. Their ages ranged between 1.1 and 47.0 years (median: 11.9 years). The cohort was subsequently subdivided into 6 groups according to age (Table 1).
Table 1 Feeding difficulties, gastrostomy, and episodes of aspiration pneumonia
Age (years) Number Meal time in minutes (mean (±SD)) Difficulty opening mouth Difficulty chewing Choking with liquids only Choking with semisolids Choking with solids only Choking on both liquids and solids Swallowing not choking Total patients with choking and/or swallowing difficulties Dietary modifications Gastrostomy Aspiration pneumonia SD, standard deviation.
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
1–5 25 28(±15.0) 2 (8%) 2 (8%) 0 0 2 (8%) 0 0 2 (8%) 2 (8%) 0 2 (8%)
6–10 30 30 (±16.5) 7 (23%) 7 (23%) 1 (3.3%) 0 2 (6.6%) 2 (6.6%) 2 (6.6%) 7 (23%) 8 (26.6%) 1 (3.3%) 1 (3.3%)
11–14 19 28 (±13.56) 4 (21%) 7 (36.8%) 0 0 1 (5.2%) 1 (5.2%) 0 2(10.5%) 4 (21%) 1 (5.2%) 0
15–19 21 28 (±16.0) 6 (28%) 4 (19%) 0 0 3 (14.2%) 0 4 (19%) 7 (33.3%) 4 (19%) 0 1 (4.7%)
20–29 13 31 (±12.1) 6 (46%) 7 (53.8%) 0 0 5 (38.4%) 1 (7.6%) 0 6 (46%) 4 (30.7%) 0 0
30–50 14 28 (±8.9) 11 (78%) 7 (50%) 1 (7.1%) 0 1 (7.1%) 3 (21.4%) 1 (7.1%) 6 (42.8%) 5 (35.7%) 1 (7.1%) 0
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choking episode but complained of swallowing difficulties. Dietary changes, mainly consisting in cutting food in smaller pieces or preference for smooth food, were recorded in 27 patients (22%) and were also more frequent in patients older than 20 years (groups 5 and 6). Duration of meal time did not increase with age. Only four patients (3%) reported episodes of proven aspiration pneumonias. There was no difference between sexes. Details of feeding difficulties are shown in Table 1. 3.3. Gastrointestinal symptoms
Fig. 1. Body weight distribution according to age. G, group.
3.1. Weight
Five of our 122 patients (4%) had been diagnosed with GER and were on medical treatment. Another 18 patients (15%) complained of recurrent abdominal pain and 9 (7%) of other symptoms that could be possibly related to GER (Table 2). 3.4. Ventilatory support
Fig. 1 shows details of the weight in the cohort in relation to age. Compared to age and sex matched controls from standardised weight charts [14], 45 out of our 122 patients (37%) showed a weight below 2SD with some patients falling as low as below 9SD. Fourteen out of the 27 patients above the age of 20 (groups 5 and 6) (50%) had weights below 2SD. Only six out of 122 patients (5%) showed a weight above 2SD and these were all below the age of 10 (groups 1 and 2). There was no difference between sexes. 3.2. Feeding difficulties Limited mouth opening and chewing difficulties were reported in 36 and in 34 out of 122 patients, respectively, (30% and 28%) and were more frequent in patients older than 20 years (groups 5 and 6). Choking episodes were reported in 23 patients (19%) and were more frequent in patients older than 20 years (groups 5 and 6). Seven patients (6%) had choking episodes with both solids and liquids, 14 (11%) with solids only and two (2%) with liquids only. Another seven patients (6%) did not report any
Four patients (3%) had tracheostomy at mean age of 26 years (range 14–38 years) (1 in group 3; 1 in group 5 and 2 in group 6) and 15 (12%) had non-invasive ventilation (NIV) at a mean age of 11 years (range 5–26 years) (Table 2). 3.5. Gastrostomy Gastrostomy was placed in three patients (2%) at mean age of 20 years (range 10–40 years) (1 in group 2; 1 in group 3 and 1 in group 6). Of those one patient did not require any ventilator support, one was on NIV and one had tracheostomy. All patients continue to regularly feed by mouth (Table 1). 3.6. Ventilatory support and feeding difficulties Feeding difficulties were present in 15 of the 103 patients (14%) without ventilatory support, in six of the 15 patients (40%) on NIV and in two of the four patients (50%) having tracheostomy.
Table 2 Gastrointestinal symptoms and ventilatory support
Age (years) Number Diagnosed GER Symptoms of GER Constipation Constipation treatment Meteorism Abdominal pain Tracheostomy NIV
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
1–5 25 0 1 (4%) 15 (60%) 14 (56%) 3 (12%) 2 (8%) 0 3 (12%)
6–10 30 0 4 (13.3%) 12 (40%) 9 (30%) 3 (10%) 6 (20%) 0 4 (13.3%)
11–14 19 2 (10.5%) 1 (5.2%) 9 (47%) 9 (47%) 1 (5.2%) 3 (15.7%) 1 (5.2%) 3 (15.7%)
15–19 21 1 (4.7%) 1 (4.7%) 9 (42.8%) 9 (42.8%) 2 (9.5%) 3 (14.2%) 0 2 (9.5%)
20–29 13 0 2 (15.3%) 4 (30.7%) 3 (23.0%) 3 (23.0%) 3 (23.0%) 1 (7.6%) 2 (15.3%)
30–50 14 2 (14.2%) 0 4 (28.5%) 4 (28.5%) 5 (35.7%) 1 (7.1%) 2 (14.2%) 1 (7.1%)
GER, gastroesophageal reflux; NIV, non-invasive ventilation.
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100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
Tracheostomy (N=3) >2SD
NIV (N=15)
No ventilatory support (N=103)
WITHIN 2SD
<2SD
Fig. 2. Ventilatory support and weight. NIV, non-invasive ventilation.
3.7. Ventilatory support and weight Fig. 2 shows the percentage of weight within 2SD, above and below 2SD in patients with tracheostomy, on nocturnal NIV and in those with no ventilatory support. 4. Discussion The aim of our study was to conduct a survey to evaluate feeding problems in a population of SMA type II patients with age between 1 and 47 years. In our cohort the most frequently reported problems were limited mouth opening and difficulties in chewing. These were present in all age groups, but were more frequent in patients older than 20 years. Predominant difficulties in the pre-oral and oral phases of deglutition have already been reported in SMA [6,9,10], but the results cannot be easily compared as previous studies included patients with different types of SMA. Furthermore, most of the previous studies were performed at a time when genetic confirmation of SMN1 deletion was not available. Our study has the advantage that our population is better characterised and more homogeneous as all our patients had a genetically confirmed diagnosis and onset, progression of the disease and maximal functional ability achieved (sitting unsupported) that were always consistent with the diagnosis of SMA type II. Swallowing difficulties were overall present in 25% of patients and reported at all ages but they were also more common in patients older than 20 years. In most of these patients the difficulties consisted in documented recurrent choking episodes with solids or with both solids and liquids. Of note 6% of our patients reported swallowing difficulties and fear rather than true occurrence of choking episodes. Because of this, most of these patients have introduced dietary modifications, such as cutting food in small pieces or preference for pureed food in order to facilitate chewing and reduce the risk of choking. In our study only four patients reported well documented aspiration pneumonias. Several other patients
had a recurrence of chest infections that were not always preceded by upper respiratory tracts infections. The results of chest X-rays however were not available to us as these acute ‘‘silent” episodes were usually managed at local hospitals, and we cannot therefore be certain of the true occurrence of signs of food aspiration. Aspiration has been reported to be frequent (68–70%) in children with severe neurological disability [15,16], but is much less frequent (approximately 6%) in patients with Duchenne Muscular Dystrophy [13]. Recent International Coordination Committee (ICC) guidelines on standards of care in SMA (ICC) have suggested that this aspect should be always examined in SMA type I, while in SMA type II patients a decision should be made according to clinical signs [17]. We were also interested to collect data regarding body weight to evaluate suboptimal and excessive weight gain at different age groups. Although we were aware that data on weight collected with a phone interview had several limitations, including the lack of consistent measurements and of other useful indexes often not routinely provided, we felt that the data could still be useful as a rough indicator of the number of patients grossly undernourished or overweight. The other limitation is that there are no normative data for patients with SMA or other neuromuscular disorders and that the measures were therefore analysed using standards charts that do not take into account muscle wasting. Even with all these limitations we found interesting that only six out of our 122 patients (5%) had a weight above 2SD for age and they were all below 10 years. Poor weight gain in contrast was more frequent, with 37% of patients having a weight below 2SD compared to age and sex matched controls from standardised weight charts [14] with approximately half of them falling below 4SD. These findings appear to be relevant even considering the limitations of the study. Although this was more frequent in patients older than 20 years (55% of patients between 21 and 47 years), it was also present in a significant number of younger patients. Not surprisingly patients with failure to thrive reported more often the association of two (22% of patients) or three (20%) problems among limited mouth opening, chewing and swallowing difficulties, than patients with weight within 2SD (9% and 2%, respectively). However the extent to which each of these factors may have contributed cannot be easily ascertained from this type of survey. As not all of these patients were followed in tertiary care centers, we also tried to examine whether the poor weight gain was associated with known possible causative factors such as nocturnal hypoventilation. On interview the great majority of our patients however reported to have routine respiratory assessments with spirometry and overnight sleep studies and there were less patients with poor weight gain in the non-ventilated group than in the groups treated with NIV or tracheostomy. We were surprised that even if poor weight gain was often associated with swallowing difficulties, only a few patients, all followed in tertiary care centers, had been
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extensively investigated with videofluoroscopy swallow studies (VFSS) or had their weight carefully monitored by dieticians or were started on dietary supplements. Only a small minority (three patients) had gastrostomy. It is even more surprising that only five patients were treated for GER, reported as a common problem in patients with SMA [17]. On direct questioning approximately 25% of patients also complained of recurrent episodes of abdominal pain, but we were not able to distinguish, on the basis of our questionnaire, a more precise location of pain or its nature. Our results should be interpreted with caution because of the design of the study. Our patients are part of a heterogeneous cohort followed in several centres, and the majority are not followed in tertiary care centers, where care can be coordinated by multidisciplinary teams. Nevertheless our findings raise a few issues about standards of care in SMA type II and suggest some considerations. Poor weight gain appears to be common in our cohort and a systematic evaluation of weight gain should be part of the routine medical examination in order to identify early signs of failure to thrive. More accurate measurements of weight together with other measures of nutritional status such as skinfold thickness should be accurately evaluated for determining comprehensive feeding strategies and recommendations. It is well recognised that malnutrition can be associated with respiratory dysfunction, blunt immunological responses and may lead to an increased risk of chest infections [18,19]. A better management of the nutritional status may thus help to reduce the number of chest infections and of hospital admissions and to improve patients quality of life. Patients should also always be carefully interviewed for symptoms of swallowing difficulties that may require VFSS to objectively assess swallowing. A more systematic approach with chest radiographs at the time of recurrent acute chest infections not necessarily preceded by upper respiratory tract infections could also be useful to document possible ‘‘silent” aspiration pneumonias. It would also be relevant to establish whether abnormal neck postures secondary to scoliosis or scoliosis surgery, could contribute to the swallowing difficulties and suboptimal weight gain in this population. Although from our findings GER does not appear to be frequent, this was not systematically evaluated and this aspect should be more appropriately addressed. Our results also suggest how an integrated multidisciplinary approach is needed in these patients in order to identify feeding difficulties and to optimise their management. At present several treatment options such as dietary modifications, adopting safe swallowing techniques, surgical interventions and enteral feeding are available, but as suggested by a recent Cochrane review on management and therapy for dysphagia in chronic muscle disease [20], systematic randomised studies are needed to establish the
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best treatment options for feeding problems in these patients. Acknowledgements We thank patients and their families and the Families of SMA Association Italy for their kind cooperation. We also thank TREAT-NMD project for the support to S.M. References [1] Dubowitz V. Disorders of the lower motor neuron: the spinal muscular atrophies. In: Dubowitz V, editor. Muscle disorders in childhood. London: Saunders; 1995. p. 325–67. [2] Dubowitz V. Chaos in the classification of SMA: a possible resolution. Neuromuscul Disord 1995;5:3–5. [3] Munsat T, Davies KE. International SMA consortium meeting, 26– 28th June 1992, Bonn, Germany. Neuromuscul Disord 1992;2:423–8. [4] Zerres K, Rudnik-Schonenborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 1995;52:518–23. [5] Tiziano FD, Bertini E, Messina S, et al. The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study. Neuromuscul Disord 2007;17:400–3. [6] Willig TN, Paulus J, Lacau Saint Guily J, Beon C, Navarro J. Swallowing problems in Neuromuscular Disorders. Arch Phys Med Rehabil 1994;75:1175–81. [7] Willig TN, Bach JR, Venance V, Navarro J. Nutritional rehabilitation in neuromuscular disorders. Semin Neurol 1995;15:18–23. [8] Tilton AH, Miller M, Khoshoo V. Nutrition and swallowing in paediatric neuromuscular patients. Semin Pediatr Neurol 1998;5:106–15. [9] Granger MW, Buschang PH, Throckmorton GS, Iannaccone ST. Masticatory muscle function in patients with spinal muscular atrophy. Am J Orthod Dentofacial Orthop 1999;115:697–702. [10] Houston K, Buschang PH, Iannaccone ST, Seale NS. Craniofacial morphology of spinal muscular atrophy. Pediatr Res 1994;36:265–9. [11] Nutman J, Nitzan M, Grunebaum M. Swallowing disturbances in Werdnig–Hoffman disease (in Hebrew). Harefuah 1981;101:301–3. [12] Grunebaum M, Nutman J, Nitzan M. The pharyngo-laryngeal deficit in the acute form of infantile spinal muscular atrophy (Werdnig– Hoffmann disease). Pediatr Radiol 1981;11:67–70. [13] Pane M, Vasta I, Messina S, et al. Feeding problems and weight gain in Duchenne muscular dystrophy. Eur J Paediatr Neurol 2006;10:231–6. [14] Kuczmarski RJ, Ogden CL, Guo SS, et al. CDC growth charts for the United States: methods and development. Vital Health Stat 2002;246:1–190. [15] Griggs GA, Findley LJ, Suratt PM, Esau SA, Wilhoit SC, Rochester DF. Prolonged relaxation rate of inspiratory muscles in patients with sleep apnea. Am Rev Respir Dis 1989;140:706–10. [16] Mirrett PL, Riski JE, Glascott J, Johnson V. Videofluoroscopic assessment of dysphagia in children with severe spastic cerebral palsy. Dysphagia 1994;9:3174–9. [17] Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A. Consensus statement for standard care in spinal muscular atrophy. J Child Neurol 2007;22:1027–49. [18] Cunningham-Rundles S. Effects of nutritional status on immunological function. Am J Clin Nutr 1982;35:1202–10. [19] Aldrich TK. Nutritional factors in the pathogenesis and therapy of respiratory insufficiency in neuromuscular diseases. Monaldi Arch Chest Dis 1993;48:327–30. [20] Hill M, Hughes T, Milford C. Treatment for swallowing difficulties (dysphagia) in chronic muscle disease. Cochrane Database Syst Rev 2004;2:CD004303.