stacy rudnicki, md kathryn and j thomas may chair in als university of arkansas for medical sciences...
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Weight Loss, Nutrition and ALS
Stacy Rudnicki, MD
Kathryn and J Thomas May Chair in ALS
University of Arkansas for Medical SciencesLittle Rock, AR
SAR has nothing to disclose
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Identify possible causes for weight loss in ALS patients
Understand total daily energy expenditure in ALS patients may be greater than expected using routine calculations
Recognize prognostic implications of early changes in BMI in ALS
Summarize the guidelines for feeding tubes in ALS patients
Compare and contrast the benefits and limitations of enteral nutrition in ALS patients
Objectives
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ALS: Disease of the Motor Neuron
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Dysphagia Muscle atrophy Depression / poor appetite Altered taste Impaired energy balance ◦Hypermetabolic state
Weight Loss in ALS Patients
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Body mass index and dietary intervention: Implications for prognosis of
amyotrophic lateral sclerosis Ngo ST, et al. J Neurol Sci 2014: 340:5-12.
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Total Daily Energy Expenditure
Sedentary Physically Active
TDEE
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80 ALS pts Measured total daily energy expenditure
(TDEE) over a 10-d period with doubly labeled water method
Estimated resting metabolic rate (RMR) using a variety of equations as well as by indirect calorimetry
Estimating daily energy expenditure in individuals with ALS Kasarskis EJ et al, Am J Clin Nutr 2014;99:792–803
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Functional motor work – increased work of using weak muscles◦Extremity muscles◦Respiratory muscles
Non-functional motor work◦Fasciculations◦Cramps ◦Spasticity◦Pseudobulbar manifestation
Metabolic cost of protein catabolism
Possible Causes for Increased Total Daily Energy Expenditure
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Used different equations for RMR Took into account muscle strength testing Used lean body mass, fat mass, BMI Included TSH, site of disease onset Different elements of the ALS-FRS-R ALSFRSR-6◦ Speech◦ Handwriting◦ Dressing and Hygiene◦ Turning in bed◦ Walking◦ Dyspnea
Modeling for more practical way to accurately estimate TDEE (18 models)
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TDEE = [Harris-Benedict RMR] + (55.96 x ALSFRS-6 Score) – 168
Harris Benedict for men◦ [66 + (13.7 x wt in kg) + (5 x ht in cm) – (6.76 x age
yrs)] Harris Benedict for women◦ [665+ (9.6 x wt in kg + (1.8 x ht in cm) – (4.7 x age
yrs)]
◦ https://mednet.mc.uky.edu/alscalculator/
Most Practical/Accurate of the Models Created to Better Estimate the TDEE
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TDEE traditional method – sedentary activity level◦1892 calories
TDEE specific for ALS◦2081 calories
56 year old male, 5’10 inches, 160 pounds, with ALS-FRS 6 score of 12
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Early Changes in BMI / Weight in ALS
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Loss of BMI > 1 from time of dx to 2 year f/u associated with shorter survival and faster rate of progression Jawaid et al. Amyotroph Lateral Scler 2008; 11:542-548
Weight loss >10% but not BMI <18.5 at time of dx associated with worse prognosis Limousin et al. J Neurol Sci 2010;297:36-39
Lowest mortality found in patients who at study entry were mildly obese (BMI 30-34.99) Paganoni et al. Muscle Nerve 2011;44:20-24
Significantly worse prognosis in patients with loss of BMI >2.5 per year (based on change in premorbid BMI compared to first visit) Shimizu T, Nagaoka et al. Amyotroph Lateral Scler 2012;13:363-366.
BMI / Weight loss and survival
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Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory 2014
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Is survival related to◦Premorbid BMI (pBMI) Increased pre-diagnostic body fat is associated
with a decreased risk of ALS mortality EPIC Cohort Neurology 2013;80:829–838
◦BMI classification at first visit (1BMI)◦Rate of change in BMI (rcBMI) rcBMI = 1BMI – pBMI / months since sxs
onset Are there clinical features that are associated
with greater rcBMI
Questions Asked
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Retrospective chart review of MND patients seen from January 2001 – February 2013
Survival recorded through April 2013 Data abstracted◦Onset site◦Time to first clinic visit (months)◦Gender◦ALS-FRS at first visit ◦Vital capacity at first visit◦Self reported premorbid weight – used to calculate
the pBMI ◦1BMI
Study Design
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Exclusions◦PLS◦Missing premorbid weight◦Transfers from another ALS clinic
BMI Classification◦<18.5 Underweight◦18.5 – 24.9 Normal weight◦25 – 29.9 Overweight◦30 + Obese
Statistical analysis done using MedCalc
Study Design
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Clinical Features (n=289)Site Onset Bulbar 86 (29.8%) Extremity 203 (70.2%)Gender Female 132 (45.7%) Male 157 (54.3%)Age of Onset 59.0 + 12.1 yearsTime to first clinic visit 12.7 + 9.2 monthsALS FRS R 36.8 + 7.6Vital Capacity (% predicted) 71.4 + 23.6BMI pBMI 28.8 + 5.8 1BMI 26.8 + 5.6
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Underweight Normal Weight
Overweight Obese0
20
40
60
80
100
120
140
pBMI
1BMI
p=0.47
p=0.94
p = 0.0028
p=0.014
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Absolute Change in BMI(kg/m2)
Range -19.3 to 5.6
Mean -2.0 + 2.8
rcBMI (kg/m2/month)
Range -2.0 to 1.53
Mean -0.21 + 0.42
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Site of Onset rcBMI P Value Bulbar -0.28 + 0.42 0.1027 Extremity -0.19 + 0.42Gender Female -0.17 + 0.29 0.1543 Male -0.24 + 0.50ALS-FRS-R < 37 -0.26 + 0.37 0.1317 > 37 -0.17 + 0.49Age of Onset < 59 years -0.19 + 0.33 0.0573* > 59 years -0.24 + 0.50Vital Capacity < 71% -0.25 + 0.34 0.0137** > 71% -0.18 + 0.37Premorbid BMI Classification Under, Normal, and Over Weight -0.15 + 0.31 0.0012** Obese -0.31 + 0.55Time to Clinic < 13 -0.26 + 0.50 0.0050** > 13 -0.12 + 0.20
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Kaplan Meier Survival AnalysispBMI Classification
p = 0.1822
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Kaplan Meier Survival Analysis1BMI Classification
p = 0.020
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Kaplan Meier Survival AnalysisrcBMI
p = 0.001
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Kaplan Meier Survival AnalysisFactor Median Survival P value
Gender Female 31 0.6192 Male 30Site of Onset Bulbar 26 0.0054* Non-bulbar 34Vital Capacity < 71% 25 <0.0001* > 71% 36ALS-FRS-R < 37 23 <0.0001* > 37 36Time to clinic < 13 24 <0.0001* > 13 37
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Covariate HazardRatio
95% CI p value
Time to clinic < 13 months
1.8140 1.3832 to 2.3791 <0.0001
Age > 59 yrs 1.7125 1.2973 to 2.2605 0.0002
rcBMI > - 0.21 1.6312 1.2395 to 2.1467 0.0005
Non Obese 1.3030 0.9437 to 1.7991 0.1096
Bulbar Onset 1.2519 0.9371 to 1.6725 0.1304
Cox Proportional Hazards Model
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Early and rapid rcBMI is a poor prognostic indicator
Bulbar onset patients did not have a significantly greater rcBMI
1BMI classification was only modestly associated with prognosis
Study limited by depending upon self reported premorbid weight
Conclusions
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What happens to rcBMI after the diagnosis? Will rcBMI improve with
Aggressive nutritional support Noninvasive ventilation
Should rcBMI be taken into account in future treatment trials?
Future Questions
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Gastrostomy in ALS
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Weight loss >10% compared to premorbid weight
VC < 50% of predicted Symptoms◦Frequent choking / evidence for aspiration◦Lengthy meals
Practical considerations
Gastrostomy Timing
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Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: Effect on survival Spartaro et al.. J Neurol Sc 2011;304:44-48
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Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: Effect on survival Spartaro et al.. J Neurol Sc 2011;304:44-48
Bulbar Onset Extremity Onset
P = 0.14PEG 28 mos no PEG 25 mos
P=.046PEG 44 mos no PEG 36 mos
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Survival curves of the RIG group( )and PEG group (-----)Chiò A et al. J Neurol Neurosurg Psychiatry 2004;75:645-647
Median survival from RIG/PEG204 days vs 85 days, p=0.004
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Gastrostomy in patients with ALS (Progas):a prospective cohort study ProGas Study Group Lancet Neurology Vol 14 Jul 2015
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Gastrostomy in patients with ALS (Progas):a prospective cohort study ProGas Study Group Lancet Neurology Vol 14 Jul 2015
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Cox Proportional Hazards Model for Survival After Gastrostomy Worse survival with◦ Greater weight loss from dx
to gastrostomy◦ Increasing age at time of dx
No differences found related to◦ VC at time of procedure◦ Procedure type
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25% gained > 1 kg 25% lost/gained < 1 kg 49% lost > 1 kg◦Continued weight loss at 3 months was associated with
poor survival
Weight Changes after Gastrostomy
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Failed placement ◦ 15.7% PEG ◦ 1.9% of RIGs
Post-procedure aspiration◦ 10.5% PEG attempts◦ 0% RIG attempts◦ Increased with worsening ALSFRS swallowing score
Gastrostomy tube placement by endoscopy vs radiologic methods in patients with ALS Allen JA. Et al Amyotrophic Lateral sclerosis & Frontotemporal Degeneration. 14(4):308-14, 2013 May.
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Survey of ALS clinics regarding enteral nutrition (EN) in patients with ALS
148 respondents (50% RDs)◦Estimated only half patients fully compliant with EN
recommendations ◦Suspected reasons for non-compliance
Side effects (fullness, diarrhea, constipation, and bloating) most common
Dependence on caregivers Rare - depression/hopelessness
◦Half estimated more than 25% of patients continued to lose weight after starting EN
Survey of current enteral nutrition practices in treatment of amyotrophic lateral sclerosisZhang M, Hubbard J, Rudnicki SA et al. Clin Nut ESPEN 2013;8:e25-28
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Diet and Survival – Animal StudiesCourtesy of Jeff Elliott MD, UTSW
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Author Diet n = Time Results
Oliveria, et al
High protein 20 6 mos
No change in muscle mass or ALS progression
Silva, et al High protein 16 4 mos
Stabilization of ALS-FRS
Dorst, et al - High fat, highcalorie- High carbohydrate, high calorie
22
16
3 mos
Wt stabilizedALS-FRS progressed
High drop out rate with High carb/high calorie
Wills, et al - High fat, high calorie (Oxepa)- High carb, high calorie (Jevity 1.5)- Control (Jevity)
8
9
7
4 mos
High carb, high calorie fewer AEs, dropouts, deaths
Is there a ‘best diet’ in ALS?
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Early changes in weight and BMI are associated with a poor prognosis in ALS
Caloric needs in ALS are likely higher than expected
Studies of survival benefits of gastrostomy ALS variable
PEG vs RIG vs PIG? Unanswered questions about
dietary recommendations in ALS
Conclusions
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Acknowledgements
UAMS ALS Team & Kara Way, MD
Work supported by the Kathryn and J Thomas May Fund for ALS