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.

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Presentation transcript:

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