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ScienceDirect Neuromuscular Disorders 25 (2015) 414–417 www.elsevier.com/locate/nmd
Surgical treatment of obesity in DM1 – a case report and a review of the literature K. Håkansson a, S. Kostic b, C. Lindberg a,* a
Neuromuscular Centre, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden b Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Received 24 September 2014; received in revised form 13 January 2015; accepted 9 February 2015
Abstract In patients with myotonic dystrophy type 1 overweight and obesity are frequent. When present this has further negative effects on the patients’ pulmonary and muscle function as well as social participation. Anesthesia in myotonic dystrophy type 1 patients is associated with increased risks, especially in those who are obese. We describe the outcome of the first patient reported who has undergone gastric bypass surgery. The operation went without complications. Within two years after surgery she has lost 56.5 kg corresponding to 44% of her preoperative body weight (128.5 kg). She has lost muscle mass and muscle strength, but has gained somewhat in functional tests including pulmonary function and has no longer any need for nocturnal ventilation. Surgical treatment of obesity may be feasible in selected myotonic dystrophy type 1 patients but further studies are needed to determine appropriate criteria for surgery including body mass index limits and how pre- and post-operative follow-up should best be made. © 2015 Elsevier B.V. All rights reserved. Keywords: Myotonic dystrophy type 1; Obesity; Anesthesia; Surgical treatment of obesity
1. Introduction Myotonic dystrophy type 1 (DM1) is the most prevalent form of muscular dystrophy in adults [1] and it is caused by a tri-nucleotide CTG repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene [2]. DM1 is a multisystem disorder that can affect several body systems such as muscle, the brain, the heart, the gastrointestinal tract, the eyes and the endocrine system [1]. In skeletal muscle there is an alternative splicing of the insulin receptor resulting in an expression of the lower-signaling muscle isoform [3]. This leads to a syndrome which includes impaired insulin sensitivity [4,5] and elevated serum levels of lipids [6]. In all forms of DM1 except the late onset/mild form, there is an increased risk of early death, the causes of which are mainly cardiac or respiratory [7,8]. In adults with DM1 there is a high prevalence of overweight (33%) and obesity (21–26%) [9,10]. Weight loss is difficult in DM1 patients. Low-caloric diet is hard for the patients to
* Corresponding author. Neuromuscular Centre, Department of Neurology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. Tel.: +46 31 3421000; fax: +46 31 7765532. E-mail address: [email protected] (C. Lindberg). http://dx.doi.org/10.1016/j.nmd.2015.02.002 0960-8966/© 2015 Elsevier B.V. All rights reserved.
manage due to their cognitive defects [11], and physical exercise is also difficult for DM1 patients due to loss of muscle strength, cognitive decline, and in some patients also cardiac and respiratory impairments. Gastric bypass is a method proven to help obese persons to loose weight [12]. In Sweden persons with a BMI > 40 kg/m2 are accepted for surgery. The typical weight loss is around 20% of their total pre-operative body weight or 70% of excess body weight [13]. In healthy individuals there is a very low perioperative morbidity and mortality [13,14]. Respiratory function deteriorates significantly in the early postoperative period in all patients [13], and obesity itself is thus associated with a risk of pulmonary complications in otherwise healthy individuals [15]. DM1 patients do, in addition to this, have an increased risk of perioperative complications during general anesthesia [16], especially in cases with upper abdominal surgery [16,17]. We are not aware of any previously reported DM1 patient who has gone through a gastric bypass operation. We describe a case with favorable outcome of gastric bypass surgery, and we discuss the perioperative risks, BMI limits used, possible short and long-term benefits as well as risks and possible side-effects by the weight loss itself and lastly how the outcome may be monitored in the future.
K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
2. Patient We describe a woman who, at age 34, underwent a laparoscopic gastric bypass in 2011. DM1 was diagnosed at 32 years of age following that her son was diagnosed with congenital DM1. DM1 is also present in her brother, her sister, her father and her aunt and the son of her aunt. The DM1 diagnosis was genetically confirmed with a CTG expansion that was 450. At age 17 the right part of her thyroid gland was extirpated due to a follicular thyroid adenoma, her thyroid function tests have thereafter been normal. In 2004 she had gone through a laparoscopic cholecystectomy. She had normal HbA1c and liver function tests as shown in Table 1. At time of surgical treatment of obesity in 2011 she had mild to moderate muscle weakness in distal muscles, but normal strength in proximal muscle groups, her muscle impairment rating scale (MIRS) classification [18] was 3. She had no signs of impaired cardiac function, ECG showed normal PQ time of 178 ms and QRS time of 88 ms. She had a severe sleep apnea syndrome, with an apnea–hypopnea index of 80/hour (normal < 5) and an Oxygen Desaturation Index (ODI) of 84/hour (severe obstructive sleep apnea syndrome if ODI > 30). She was treated with nocturnal home-ventilation with a Bi-level positive airway pressure (BiPAP) since age 33, i.e. the last year before the operation. Our patient has been overweight since age 20. Before her first pregnancy at age 26 her weight was 90 kg (length 162 cm, BMI 35 kg/m2) and after her second pregnancy when she was 29 years old her bodyweight was 120 kg (BMI 45,5 kg/m2), and just prior to the gastric bypass operation her bodyweight was 128.5 (BMI 49 kg/m2). She has, without success, tried several diet programs including the low calorie diet (LCD) which is mandatory for all patients to try before surgical treatment of obesity. 3. Results 3.1. Surgery procedure The operation was performed in Nov 2011. General anesthesia was used. The surgical method was gastric bypass by
415
laparoscopy as described previously [13]. The gastrojejunostomy (GE) was created by stapling the jejunum to the posterior wall of the gastric pouch using a 45 mm 3.5-mmstaple linear cutting stapler. The remaining defect was sutured with two running resorbable 3/0 sutures anchored at both staple-line edges. The entero-entero-anastomosis (EEA) was created in a similar manner as a side-to-side anastomosis with 45–60 mm 3.5-mm stapler. The length of the Roux limb was chosen to be 120 cm. To complete the Roux-en-Y construction, the loop was divided with a linear cutting stapler between the anastomosis. There were no peri- or postoperative complications. 3.2. Outcome Her pre- and postoperative body-weight and BMI appear in Fig. 1. One year after the operation, she weighed 83 kg with a corresponding BMI of 31.2 kg/m2 and had thus lost 45 kg. At the follow-up in 2013 her body weight was 72 kg (BMI 29 kg/m2) and she had thus lost 44% of her initial bodyweight. Body mass composition was measured using dual-energy X-ray absorptiometry (DXA) which showed a reduction of body fat but also fat-free mass (Fig. 1). She no longer had any use for her nocturnal BiPAP ventilation, she had clearly less daytime fatigue, and had no longer any need for an afternoon nap. She had managed to start part-time work. Her FVC sitting was slightly higher at follow up (2.9 liters compared to 2.6 liters). We found that her muscle strength measured by a hand-held myometer [19] had decreased somewhat 2 years after the operation in most of the measured muscle functions (Table 2). This contrasts to the findings in the functional tests as walking 10 m maximum speed that increased slightly from 1.5 m/s to 1.7 m/s and the number of steps performed in the step test [20] had increased from 13.5 to 18 steps. During the last follow-up in Feb 2014, 2 years and 3 months after the operation, her weight was 70 kg and her FVC sitting was 3.0 liters (Fig. 1). Laboratory parameters appear in Table 1. Her total serum cholesterol and low density lipoprotein (LDL) levels as well as triglycerides had decreased, while the other measures were unchanged.
Table 1 Laboratory parameters – pre- and post the surgical treatment of obesity performed in November 2011 in a 34 year old female patient with DM1.
s-Cholesterol (3.3–6.9 mmol/L) s-LDL (1.4–4.7 mmol/L) s-HDL (1.0–2.7 mmol/L) s-Triglycerides (0.45–2.6 mmol/L) s-Creatinine (45–90 mol/L) s-Cystatin C (0.47–1.09 mg/L) s-HbA1c (27–42 mmol/mol) s-AST (0.25–0.60 µkat/L) s-ALT (0.15–0.75 µkat/L) s-ALP (0.6–1.8 µkat/L) s-Bilirubin (5–25 µmol/L)
Nov-10
Oct-11
Nov-12
5.3 3.5 0.85 2.5
5.2 3.6 0.92 1.8 65 1.22 28 0.99 0.78 1.4 6.6
4.0 2.5 0.9 1.26 55
1.05 26
1.8 9.3
25 0.66 0.48
Jan-13
Jan-14
3.5 2.1
3.2
1.1 57 1.19 24
1.4
1.3
26 0.45 0.28 1.1 6.8
Abbreviations: LDL: low-density lipoprotein, HDL: high-density lipoprotein, HbA1c: glycated hemoglobulin, AST: aspartate transaminase, ALT: alanine transaminase, ALP: alkaline phosphatase, L: liter.
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K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
Body weight (kg) 140 120 100 80
Lean body mass 50 kg Body fat 80 kg
60 Lean body mass 42 kg Body fat 30 kg
40 Operation
20
no v10 ja n11 m ar -1 m 1 aj -1 1 ju l-1 se 1 p11 no v11 ja n1 m 2 ar -1 m 2 aj -1 2 ju l-1 se 2 p12 no v12 ja n13 m ar -1 m 3 aj -1 3 ju l-1 se 3 p13
0
Fig. 1. The figure shows, in a woman with DM1, changes in body weight in kg, lean body mass and body fat (measured by DXA) in relation to a gastric bypass operation performed in November 2011.
4. Discussion
4.2. BMI limit for surgery
Our case-report illustrates that in a DM1 patient a significant weight loss can be achieved after surgical treatment of obesity without complications. Further, our patient showed slight improvement in the gait and step test, improved serum lipid levels, and our patient also reported improved fatigue, improved participation and quality of life.
In Sweden there is a lower limit for acceptance of surgical treatment of obesity at BMI of 40 kg/m2 in patients without diabetes. However, based on DXA studies in patients with various neuromuscular disorders including DM1, it has been shown that they have a lower fat-free body mass and higher fat content than normal controls [25]. By using DXA it was shown that DM1 patients had lower regional fat-free mass index and higher fat mass index (FMI) as compared to controls, and that the FMI increases with increased muscular disability rating in DM1 patients [25]. Thus, it is our opinion that neuromuscular patients with BMI lower than 40 kg/m2 should be accepted for surgery. When considering the timing it should be borne in mind that muscle strength and function decrease over time in DM1 patients [26]. Whether a DXA should be used as a guidance and what figures of limits should be used is to be a matter of discussion and perhaps also for future studies.
4.1. Anesthetic risks Surgery under general anesthesia in DM1 patients is associated with a significantly increased risk of mainly respiratory post- or perioperative complications [16,21,22], in particular in the case of upper abdominal surgery and is also higher in the patients with increasing proximal muscle weakness [16], in particular MIRS = 5 [23]. This risk of complications may be reduced with careful monitoring and alternative anesthetic regimes [24].
4.3. Risk of sarcopenia? Table 2 Muscle strength and function measured one year before and 14 months after obesity surgery, performed in November 2011, in a 34 year old woman with DM1 showing that although she had lost muscle strength she had gained in functional tests and FVC. Step test (mean right and left)a Walking speed (m/s) FVC sitting (liters (% predicted)) FVC supine (liters) Myometryb Hip flexion (newton (% normal)) Knee extension (newton (% normal)) Elbow flexion (newton (% normal)) Elbow extension (newton (% normal)) Wrist extension (newton (% normal))
Oct-10
Jan-13
13,5 1,5 2.6 (77%) 2.5
18 1,7 2.9 (86%) 2.6
179 (97%) 327 (107%) 203 (102%) 106 (72%) 107 (55%)
158 (85%) 311 (102%) 162 (82%) 70 (47%) 111 (57%)
FVC: forced vital capacity. a Step test according to Hill et al. [20]. b Myometry according to Phillips et al. [19].
There is a rapid weight loss seen in healthy individuals after obesity surgery – typically 20% of pre-operative body weight during the first year. When this happens in DM1 patients, does this negatively affect DM1 patients’ muscle strength and function? Theoretically this may be an important risk since the degenerative process in DM1 muscle resembles that of the age related sarcopenia [27–29]. If this is the case, it may be an argument against surgical treatment of obesity as a way to loose weight. Prospective studies including muscle strength, muscle function and perhaps also DXA may shed light on this important issue. In our case we found a loss of muscle mass measured by DXA and also a loss of muscle strength measured by manual myometry, but found no signs of deterioration of gait or mobility by our measures or as reported by our patient. On the contrary she gained in several functional tests.
K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
4.4. Short and long-term benefits There are several potential benefits of weight loss. Improved blood glucose handling and reduction in serum lipids reduce the risk of diabetes and atherosclerosis. This is found in healthy individuals, and it remains to be proven that this is a finding also in DM1 patients and that it is persistent over time. Lower body weight makes it easier for the patients to move, and perhaps this can make them motivated to participate in physical activities. Inactivity is identified as one of the major factors that contribute to fatigue and loss of cognitive and social functioning often seen in DM1 patients. Improvement in respiratory function is of benefit, and may have the potential to reduce early death in this patient group, given that a substantial proportion of deaths are presumed to be primarily respiratory. 4.5. Conclusions and aspects for the future We present a case with a favorable outcome of laparoscopic gastric bypass surgery in a DM1 patient. It is known that DM1 patients are inactive, some 20 percent of cases are obese, and that traditional weight reduction i.e. physical exercise and/or diet is seldom beneficial. The patients have a reduced amount of fat-free body mass, and thus we suggest that the BMI levels used for acceptance for obesity surgery should be lower than that used in healthy individuals – but to which extent need to be investigated. Monitoring of muscle strength and function preand postoperatively can give us more knowledge if there is a clinically significant sarcopenia as a result of rapid weight loss following the operation. Every operation is a risk, and the patients’ potential benefits should be carefully compared to his or her perioperative risk. Further prospective studies are needed in order to see if the observed positive effects are present over time in this patient group, as it is in otherwise healthy patients. These aspects are probably valid also in patients with other neuromuscular diseases. References [1] Harper P.S., Monckton P.G. Myotonic dystrophy. In: Engel A.G., Franzini-Amstrong C., editors. Myology. Basic and clinical, vol. 2. 3rd ed. New York: McGraw-Hill; 2005. p. 1039–76. [2] Harley H.G., Brook J.D., Rundle S.A., et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 1992;355:545–6. [3] Savkur R.S., Philips A.V., Cooper T.A. Aberrant regulations of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 2001;29:40–7. [4] Moxley R.T. 3rd, Griggs R.C., Goldblatt D., VanGelder V., Herr B.E. Decreased insulin sensitivity of forearm muscle in myotonic dystrophy. J Clin Invest 1978;62:857–67. [5] Moxley R.T., Corbett A.J., Minaker K.L., Rowe J.W. Whole body insulin resistance in myotonic dystrophy. Ann Neurol 1984;15:157–62. [6] Daniele A., De Rosa A., De Cristofaro M., et al. Decreased concentration of adiponectin together with a selective reduction of its high molecular weight oligomers is involved in metabolic complications of myotonic dystrophy type 1. Eur J Endocrinol 2011;165:969–75. [7] Mathieu J., Allard P., Potvin L., Prevost C., Begin P. A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology 1999;52:1658–62.
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[8] Bhakta D., Groh M.R., Shen C., Pascuzzi R.M., Groh W.J. Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1. Am Heart J 2010;160:1137–41. [9] Gagnon C., Chouinard M.C., Laberge L., et al. Prevalence of lifestyle risk factors in myotonic dystrophy type 1. Can J Neurol Sci 2013;40: 42–7. [10] Kaminsky P., Poussel M., Pruna L., Deibener J., Chenuel B., Brembilla-Perrot B. Organ dysfunction and muscular disability in myotonic dystrophy type 1. Medicine (Baltimore) 2011;90:262–8. [11] Winblad S., Lindberg C., Hansen S. Cognitive deficits and CTG repeat expansion size in classical myotonic dystrophy (DM1). Behav Brain Funct 2006;2:16. [12] Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery. J Intern Med 2013;273:219–34. [13] Olbers T., Lönroth H., Fagervik-Olsén M., Lundell L. Laparoscopic gastric bypass: development of technique, respiratory function, and lon-term outcome. Obes Surg 2003;13:364–70. [14] Sucandy I., Antanavicius G. Impact of minimally invasive/bariatric surgery fellowship on perioperative complications and outcomes in the first year of practice. N Am J Med Sci 2013;5:419–21. [15] Mitchell J.E., Lancaster K.L., Burgard M.A., et al. Long-term follow-up of patients’ status after gastric bypass. Obes Surg 2001;11:464–8. [16] Mathieu J., Allard P., Gobeil G., Girard M., De Baekeleer M., Bégin P. Anesthetic and surgical complications in 219 cases with myotonic dystrophy. Neurology 1997;49:1646–50. [17] Bisinotto F.M., Fabri D.C., Calcado M.S., Perfeito P.B., Tostes L.V., Sousa G.D. Anesthesia for video laparoscopic cholecystectomy in a patient with Steinert disease. Case report and review of the literature. Rev Bras Anestesiol 2010;60:181–91. [18] Mathieu J., Boivin H., Meunier D., Gaudreault M., Bégin P. Assessment of a disease-specific muscular impairment rating scale in myotonic dystrophy. Neurology 2001;56:336–40. [19] Phillips B.A., Lo S.K., Mastaglia F.L. Muscle force measured using “break” testing with a hand-held myometer in normal subjects aged 20 to 69 years. Arch Phys Med Rehabil 2000;81:653–61. [20] Hill K.D., Bernhardt J., McGann A.M., Maltese D., Berkovits D. A new test of dynamic standing balance for stroke patients: reliability, validity and comparison with healthy elderly. Physiother Can 1996;257–62. [21] Aldridge L.M. Anaesthetic problems in myotonic dystrophy. A case report and review of the Aberdeen experience comprising 48 general anaesthetics in a further 16 patients. Br J Anaesth 1985;57: 1119–30. [22] Veyckemans F., Scholtes J.-L. Myotonic dystrophies type 1 and 2: anesthetic care. Paediatr Anaesth 2013;23:794–803. [23] Sinclair J.L., Reed P.W. Risk factors for peri-operative adverse events in children with myotonic dystrophy. Paediatr Anaesth 2009;19:740–7. [24] Urciuoli P., Buonopane C.E., Sottile D., et al. Laparoscopic cholecystectomy in Steinert’s myotonic dystrophy. About two clinical cases. Ann Ital Chir 2014;85:385–8. [25] Pruna L., Chatelin J., Pascal-Vigneron V., Kaminsky P. Regional body composition and functional impairment in patients with myotonic dystrophy. Muscle Nerve 2011;44:503–8. [26] Mathieu J., Boivin H., Richards C.L. Quantitative motor assessment in myotonic dystrophy. Can J Neurol Sci 2003;30:129–36. [27] Malatesta M. Skeletal muscle features in myotonic dystrophy and sarcopenia: do similar nuclear mechanisms lead to skeletal muscle wasting? Eur J Histochem 2012;56:e36. [28] Malatesta M., Giagnacovo M., Costanzo M., Cisterna B., Cardani R., Meola G. Muscleblind-like1 undergoes ectopic relocation in the nuclei of skeletal muscles in myotonic dystrophy and sarcopenia. Eur J Histochem 2013;57:e15. [29] Malatesta M., Cardani R., Pellicciari C., Meola G. RNA transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia: the ultrastructural evidence. Front Aging Neurosci 2014;6:196.
ScienceDirect Neuromuscular Disorders 25 (2015) 414–417 www.elsevier.com/locate/nmd
Surgical treatment of obesity in DM1 – a case report and a review of the literature K. Håkansson a, S. Kostic b, C. Lindberg a,* a
Neuromuscular Centre, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden b Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Received 24 September 2014; received in revised form 13 January 2015; accepted 9 February 2015
Abstract In patients with myotonic dystrophy type 1 overweight and obesity are frequent. When present this has further negative effects on the patients’ pulmonary and muscle function as well as social participation. Anesthesia in myotonic dystrophy type 1 patients is associated with increased risks, especially in those who are obese. We describe the outcome of the first patient reported who has undergone gastric bypass surgery. The operation went without complications. Within two years after surgery she has lost 56.5 kg corresponding to 44% of her preoperative body weight (128.5 kg). She has lost muscle mass and muscle strength, but has gained somewhat in functional tests including pulmonary function and has no longer any need for nocturnal ventilation. Surgical treatment of obesity may be feasible in selected myotonic dystrophy type 1 patients but further studies are needed to determine appropriate criteria for surgery including body mass index limits and how pre- and post-operative follow-up should best be made. © 2015 Elsevier B.V. All rights reserved. Keywords: Myotonic dystrophy type 1; Obesity; Anesthesia; Surgical treatment of obesity
1. Introduction Myotonic dystrophy type 1 (DM1) is the most prevalent form of muscular dystrophy in adults [1] and it is caused by a tri-nucleotide CTG repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene [2]. DM1 is a multisystem disorder that can affect several body systems such as muscle, the brain, the heart, the gastrointestinal tract, the eyes and the endocrine system [1]. In skeletal muscle there is an alternative splicing of the insulin receptor resulting in an expression of the lower-signaling muscle isoform [3]. This leads to a syndrome which includes impaired insulin sensitivity [4,5] and elevated serum levels of lipids [6]. In all forms of DM1 except the late onset/mild form, there is an increased risk of early death, the causes of which are mainly cardiac or respiratory [7,8]. In adults with DM1 there is a high prevalence of overweight (33%) and obesity (21–26%) [9,10]. Weight loss is difficult in DM1 patients. Low-caloric diet is hard for the patients to
* Corresponding author. Neuromuscular Centre, Department of Neurology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. Tel.: +46 31 3421000; fax: +46 31 7765532. E-mail address: [email protected] (C. Lindberg). http://dx.doi.org/10.1016/j.nmd.2015.02.002 0960-8966/© 2015 Elsevier B.V. All rights reserved.
manage due to their cognitive defects [11], and physical exercise is also difficult for DM1 patients due to loss of muscle strength, cognitive decline, and in some patients also cardiac and respiratory impairments. Gastric bypass is a method proven to help obese persons to loose weight [12]. In Sweden persons with a BMI > 40 kg/m2 are accepted for surgery. The typical weight loss is around 20% of their total pre-operative body weight or 70% of excess body weight [13]. In healthy individuals there is a very low perioperative morbidity and mortality [13,14]. Respiratory function deteriorates significantly in the early postoperative period in all patients [13], and obesity itself is thus associated with a risk of pulmonary complications in otherwise healthy individuals [15]. DM1 patients do, in addition to this, have an increased risk of perioperative complications during general anesthesia [16], especially in cases with upper abdominal surgery [16,17]. We are not aware of any previously reported DM1 patient who has gone through a gastric bypass operation. We describe a case with favorable outcome of gastric bypass surgery, and we discuss the perioperative risks, BMI limits used, possible short and long-term benefits as well as risks and possible side-effects by the weight loss itself and lastly how the outcome may be monitored in the future.
K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
2. Patient We describe a woman who, at age 34, underwent a laparoscopic gastric bypass in 2011. DM1 was diagnosed at 32 years of age following that her son was diagnosed with congenital DM1. DM1 is also present in her brother, her sister, her father and her aunt and the son of her aunt. The DM1 diagnosis was genetically confirmed with a CTG expansion that was 450. At age 17 the right part of her thyroid gland was extirpated due to a follicular thyroid adenoma, her thyroid function tests have thereafter been normal. In 2004 she had gone through a laparoscopic cholecystectomy. She had normal HbA1c and liver function tests as shown in Table 1. At time of surgical treatment of obesity in 2011 she had mild to moderate muscle weakness in distal muscles, but normal strength in proximal muscle groups, her muscle impairment rating scale (MIRS) classification [18] was 3. She had no signs of impaired cardiac function, ECG showed normal PQ time of 178 ms and QRS time of 88 ms. She had a severe sleep apnea syndrome, with an apnea–hypopnea index of 80/hour (normal < 5) and an Oxygen Desaturation Index (ODI) of 84/hour (severe obstructive sleep apnea syndrome if ODI > 30). She was treated with nocturnal home-ventilation with a Bi-level positive airway pressure (BiPAP) since age 33, i.e. the last year before the operation. Our patient has been overweight since age 20. Before her first pregnancy at age 26 her weight was 90 kg (length 162 cm, BMI 35 kg/m2) and after her second pregnancy when she was 29 years old her bodyweight was 120 kg (BMI 45,5 kg/m2), and just prior to the gastric bypass operation her bodyweight was 128.5 (BMI 49 kg/m2). She has, without success, tried several diet programs including the low calorie diet (LCD) which is mandatory for all patients to try before surgical treatment of obesity. 3. Results 3.1. Surgery procedure The operation was performed in Nov 2011. General anesthesia was used. The surgical method was gastric bypass by
415
laparoscopy as described previously [13]. The gastrojejunostomy (GE) was created by stapling the jejunum to the posterior wall of the gastric pouch using a 45 mm 3.5-mmstaple linear cutting stapler. The remaining defect was sutured with two running resorbable 3/0 sutures anchored at both staple-line edges. The entero-entero-anastomosis (EEA) was created in a similar manner as a side-to-side anastomosis with 45–60 mm 3.5-mm stapler. The length of the Roux limb was chosen to be 120 cm. To complete the Roux-en-Y construction, the loop was divided with a linear cutting stapler between the anastomosis. There were no peri- or postoperative complications. 3.2. Outcome Her pre- and postoperative body-weight and BMI appear in Fig. 1. One year after the operation, she weighed 83 kg with a corresponding BMI of 31.2 kg/m2 and had thus lost 45 kg. At the follow-up in 2013 her body weight was 72 kg (BMI 29 kg/m2) and she had thus lost 44% of her initial bodyweight. Body mass composition was measured using dual-energy X-ray absorptiometry (DXA) which showed a reduction of body fat but also fat-free mass (Fig. 1). She no longer had any use for her nocturnal BiPAP ventilation, she had clearly less daytime fatigue, and had no longer any need for an afternoon nap. She had managed to start part-time work. Her FVC sitting was slightly higher at follow up (2.9 liters compared to 2.6 liters). We found that her muscle strength measured by a hand-held myometer [19] had decreased somewhat 2 years after the operation in most of the measured muscle functions (Table 2). This contrasts to the findings in the functional tests as walking 10 m maximum speed that increased slightly from 1.5 m/s to 1.7 m/s and the number of steps performed in the step test [20] had increased from 13.5 to 18 steps. During the last follow-up in Feb 2014, 2 years and 3 months after the operation, her weight was 70 kg and her FVC sitting was 3.0 liters (Fig. 1). Laboratory parameters appear in Table 1. Her total serum cholesterol and low density lipoprotein (LDL) levels as well as triglycerides had decreased, while the other measures were unchanged.
Table 1 Laboratory parameters – pre- and post the surgical treatment of obesity performed in November 2011 in a 34 year old female patient with DM1.
s-Cholesterol (3.3–6.9 mmol/L) s-LDL (1.4–4.7 mmol/L) s-HDL (1.0–2.7 mmol/L) s-Triglycerides (0.45–2.6 mmol/L) s-Creatinine (45–90 mol/L) s-Cystatin C (0.47–1.09 mg/L) s-HbA1c (27–42 mmol/mol) s-AST (0.25–0.60 µkat/L) s-ALT (0.15–0.75 µkat/L) s-ALP (0.6–1.8 µkat/L) s-Bilirubin (5–25 µmol/L)
Nov-10
Oct-11
Nov-12
5.3 3.5 0.85 2.5
5.2 3.6 0.92 1.8 65 1.22 28 0.99 0.78 1.4 6.6
4.0 2.5 0.9 1.26 55
1.05 26
1.8 9.3
25 0.66 0.48
Jan-13
Jan-14
3.5 2.1
3.2
1.1 57 1.19 24
1.4
1.3
26 0.45 0.28 1.1 6.8
Abbreviations: LDL: low-density lipoprotein, HDL: high-density lipoprotein, HbA1c: glycated hemoglobulin, AST: aspartate transaminase, ALT: alanine transaminase, ALP: alkaline phosphatase, L: liter.
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K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
Body weight (kg) 140 120 100 80
Lean body mass 50 kg Body fat 80 kg
60 Lean body mass 42 kg Body fat 30 kg
40 Operation
20
no v10 ja n11 m ar -1 m 1 aj -1 1 ju l-1 se 1 p11 no v11 ja n1 m 2 ar -1 m 2 aj -1 2 ju l-1 se 2 p12 no v12 ja n13 m ar -1 m 3 aj -1 3 ju l-1 se 3 p13
0
Fig. 1. The figure shows, in a woman with DM1, changes in body weight in kg, lean body mass and body fat (measured by DXA) in relation to a gastric bypass operation performed in November 2011.
4. Discussion
4.2. BMI limit for surgery
Our case-report illustrates that in a DM1 patient a significant weight loss can be achieved after surgical treatment of obesity without complications. Further, our patient showed slight improvement in the gait and step test, improved serum lipid levels, and our patient also reported improved fatigue, improved participation and quality of life.
In Sweden there is a lower limit for acceptance of surgical treatment of obesity at BMI of 40 kg/m2 in patients without diabetes. However, based on DXA studies in patients with various neuromuscular disorders including DM1, it has been shown that they have a lower fat-free body mass and higher fat content than normal controls [25]. By using DXA it was shown that DM1 patients had lower regional fat-free mass index and higher fat mass index (FMI) as compared to controls, and that the FMI increases with increased muscular disability rating in DM1 patients [25]. Thus, it is our opinion that neuromuscular patients with BMI lower than 40 kg/m2 should be accepted for surgery. When considering the timing it should be borne in mind that muscle strength and function decrease over time in DM1 patients [26]. Whether a DXA should be used as a guidance and what figures of limits should be used is to be a matter of discussion and perhaps also for future studies.
4.1. Anesthetic risks Surgery under general anesthesia in DM1 patients is associated with a significantly increased risk of mainly respiratory post- or perioperative complications [16,21,22], in particular in the case of upper abdominal surgery and is also higher in the patients with increasing proximal muscle weakness [16], in particular MIRS = 5 [23]. This risk of complications may be reduced with careful monitoring and alternative anesthetic regimes [24].
4.3. Risk of sarcopenia? Table 2 Muscle strength and function measured one year before and 14 months after obesity surgery, performed in November 2011, in a 34 year old woman with DM1 showing that although she had lost muscle strength she had gained in functional tests and FVC. Step test (mean right and left)a Walking speed (m/s) FVC sitting (liters (% predicted)) FVC supine (liters) Myometryb Hip flexion (newton (% normal)) Knee extension (newton (% normal)) Elbow flexion (newton (% normal)) Elbow extension (newton (% normal)) Wrist extension (newton (% normal))
Oct-10
Jan-13
13,5 1,5 2.6 (77%) 2.5
18 1,7 2.9 (86%) 2.6
179 (97%) 327 (107%) 203 (102%) 106 (72%) 107 (55%)
158 (85%) 311 (102%) 162 (82%) 70 (47%) 111 (57%)
FVC: forced vital capacity. a Step test according to Hill et al. [20]. b Myometry according to Phillips et al. [19].
There is a rapid weight loss seen in healthy individuals after obesity surgery – typically 20% of pre-operative body weight during the first year. When this happens in DM1 patients, does this negatively affect DM1 patients’ muscle strength and function? Theoretically this may be an important risk since the degenerative process in DM1 muscle resembles that of the age related sarcopenia [27–29]. If this is the case, it may be an argument against surgical treatment of obesity as a way to loose weight. Prospective studies including muscle strength, muscle function and perhaps also DXA may shed light on this important issue. In our case we found a loss of muscle mass measured by DXA and also a loss of muscle strength measured by manual myometry, but found no signs of deterioration of gait or mobility by our measures or as reported by our patient. On the contrary she gained in several functional tests.
K. Håkansson et al. / Neuromuscular Disorders 25 (2015) 414–417
4.4. Short and long-term benefits There are several potential benefits of weight loss. Improved blood glucose handling and reduction in serum lipids reduce the risk of diabetes and atherosclerosis. This is found in healthy individuals, and it remains to be proven that this is a finding also in DM1 patients and that it is persistent over time. Lower body weight makes it easier for the patients to move, and perhaps this can make them motivated to participate in physical activities. Inactivity is identified as one of the major factors that contribute to fatigue and loss of cognitive and social functioning often seen in DM1 patients. Improvement in respiratory function is of benefit, and may have the potential to reduce early death in this patient group, given that a substantial proportion of deaths are presumed to be primarily respiratory. 4.5. Conclusions and aspects for the future We present a case with a favorable outcome of laparoscopic gastric bypass surgery in a DM1 patient. It is known that DM1 patients are inactive, some 20 percent of cases are obese, and that traditional weight reduction i.e. physical exercise and/or diet is seldom beneficial. The patients have a reduced amount of fat-free body mass, and thus we suggest that the BMI levels used for acceptance for obesity surgery should be lower than that used in healthy individuals – but to which extent need to be investigated. Monitoring of muscle strength and function preand postoperatively can give us more knowledge if there is a clinically significant sarcopenia as a result of rapid weight loss following the operation. Every operation is a risk, and the patients’ potential benefits should be carefully compared to his or her perioperative risk. Further prospective studies are needed in order to see if the observed positive effects are present over time in this patient group, as it is in otherwise healthy patients. These aspects are probably valid also in patients with other neuromuscular diseases. References [1] Harper P.S., Monckton P.G. Myotonic dystrophy. In: Engel A.G., Franzini-Amstrong C., editors. Myology. Basic and clinical, vol. 2. 3rd ed. New York: McGraw-Hill; 2005. p. 1039–76. [2] Harley H.G., Brook J.D., Rundle S.A., et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 1992;355:545–6. [3] Savkur R.S., Philips A.V., Cooper T.A. Aberrant regulations of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 2001;29:40–7. [4] Moxley R.T. 3rd, Griggs R.C., Goldblatt D., VanGelder V., Herr B.E. Decreased insulin sensitivity of forearm muscle in myotonic dystrophy. J Clin Invest 1978;62:857–67. [5] Moxley R.T., Corbett A.J., Minaker K.L., Rowe J.W. Whole body insulin resistance in myotonic dystrophy. Ann Neurol 1984;15:157–62. [6] Daniele A., De Rosa A., De Cristofaro M., et al. Decreased concentration of adiponectin together with a selective reduction of its high molecular weight oligomers is involved in metabolic complications of myotonic dystrophy type 1. Eur J Endocrinol 2011;165:969–75. [7] Mathieu J., Allard P., Potvin L., Prevost C., Begin P. A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology 1999;52:1658–62.
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