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

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

ALS: Disease of the Motor Neuron

Dysphagia Muscle atrophy Depression / poor appetite Altered taste Impaired energy balance ◦Hypermetabolic state

Weight Loss in ALS Patients

Body mass index and dietary intervention: Implications for prognosis of

amyotrophic lateral sclerosis Ngo ST, et al. J Neurol Sci 2014: 340:5-12.

Total Daily Energy Expenditure

Sedentary Physically Active

TDEE

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

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

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)

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

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

Early Changes in BMI / Weight in ALS

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

Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory 2014

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

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

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

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

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

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

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

Kaplan Meier Survival AnalysispBMI Classification

p = 0.1822

Kaplan Meier Survival Analysis1BMI Classification

p = 0.020

Kaplan Meier Survival AnalysisrcBMI

p = 0.001

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

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

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

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

Gastrostomy in ALS

Weight loss >10% compared to premorbid weight

VC < 50% of predicted Symptoms◦Frequent choking / evidence for aspiration◦Lengthy meals

Practical considerations

Gastrostomy Timing

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: Effect on survival Spartaro et al.. J Neurol Sc 2011;304:44-48

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

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

Gastrostomy in patients with ALS (Progas):a prospective cohort study ProGas Study Group Lancet Neurology Vol 14 Jul 2015

Gastrostomy in patients with ALS (Progas):a prospective cohort study ProGas Study Group Lancet Neurology Vol 14 Jul 2015

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

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

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.

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

Diet and Survival – Animal StudiesCourtesy of Jeff Elliott MD, UTSW

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?

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

Acknowledgements

UAMS ALS Team & Kara Way, MD

Work supported by the Kathryn and J Thomas May Fund for ALS