Stacy Rudnicki, MD Kathryn and J Thomas May Chair in ALS University of Arkansas for Medical Sciences Little 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
Dysphagia Muscle atrophy Depression / poor appetite Altered taste Impaired energy balance ◦ Hypermetabolic state
Body mass index and dietary intervention: Implications for prognosis of amyotrophic lateral sclerosis Ngo ST, et al. J Neurol Sci 2014: 340:5-12.
SedentaryPhysically Active
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
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
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
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)] ◦
TDEE traditional method – sedentary activity level ◦ 1892 calories TDEE specific for ALS ◦ 2081 calories
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: 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 ) 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:
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
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
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
Clinical Features (n=289) Site Onset Bulbar86 (29.8%) Extremity203 (70.2%) Gender Female132 (45.7%) Male157 (54.3%) Age of Onset years Time to first clinic visit months ALS FRS R Vital Capacity (% predicted) BMI pBMI BMI
Absolute Change in BMI (kg/m 2 ) Range-19.3 to 5.6 Mean rcBMI (kg/m 2 /month) Range-2.0 to 1.53 Mean
Site of OnsetrcBMIP Value Bulbar Extremity Gender Female Male ALS-FRS-R < > Age of Onset < 59 years * > 59 years Vital Capacity < 71% ** > 71% Premorbid BMI Classification Under, Normal, and Over Weight ** Obese Time to Clinic < ** >
p =
p = 0.020
p = 0.001
Kaplan Meier Survival Analysis FactorMedian SurvivalP value Gender Female Male30 Site of Onset Bulbar * Non-bulbar34 Vital Capacity < 71%25<0.0001* > 71%36 ALS-FRS-R < 3723<0.0001* > 3736 Time to clinic < 1324<0.0001* > 1337
Covariate Hazard Ratio 95% CIp value Time to clinic < 13 months to < Age > 59 yrs to rcBMI > to Non Obese to Bulbar Onset to
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
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?
Weight loss >10% compared to premorbid weight VC < 50% of predicted Symptoms ◦ Frequent choking / evidence for aspiration ◦ Lengthy meals Practical considerations
P = 0.14 PEG 28 mos no PEG 25 mos P=.046 PEG 44 mos no PEG 36 mos
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
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
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
AuthorDietn =TimeResults Oliveria, et al High protein206 mos No change in muscle mass or ALS progression Silva, et alHigh protein164 mos Stabilization of ALS-FRS Dorst, et al- High fat, high calorie - High carbohydrate, high calorie mos Wt stabilized ALS-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) mos High carb, high calorie fewer AEs, dropouts, deaths
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
UAMS ALS Team & Kara Way, MD Work supported by the Kathryn and J Thomas May Fund for ALS