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.
TDEE
Sedentary
Physically 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)]
◦ https://mednet.mc.uky.edu/alscalculator/

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; 11:542-548

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.

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
Bulbar
Extremity
Gender
Female
Male
Age of Onset
Time to first clinic visit
ALS FRS R
Vital Capacity (% predicted)
BMI
pBMI
1BMI
86 (29.8%)
203 (70.2%)
132 (45.7%)
157 (54.3%)
59.0 + 12.1 years
12.7 + 9.2 months
36.8 + 7.6
71.4 + 23.6
28.8 + 5.8
26.8 + 5.6
140
p=0.94
120
p = 0.0028
100
p=0.47
80
pBMI
1BMI
60
40
20
p=0.014
0
Underweight
Normal
Weight
Overweight
Obese
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
Bulbar
Extremity
Gender
Female
Male
ALS-FRS-R
< 37
> 37
Age of Onset
< 59 years
> 59 years
Vital Capacity
< 71%
> 71%
Premorbid BMI Classification
Under, Normal, and Over Weight
Obese
Time to Clinic
< 13
> 13
rcBMI
-0.28 + 0.42
-0.19 + 0.42
P Value
0.1027
-0.17 + 0.29
-0.24 + 0.50
0.1543
-0.26 + 0.37
-0.17 + 0.49
0.1317
-0.19 + 0.33
-0.24 + 0.50
0.0573*
-0.25 + 0.34
-0.18 + 0.37
0.0137**
-0.15 + 0.31
-0.31 + 0.55
0.0012**
-0.26 + 0.50
-0.12 + 0.20
0.0050**
p = 0.1822
p = 0.020
p = 0.001
Kaplan Meier Survival Analysis
Factor
Gender
Female
Male
Site of Onset
Bulbar
Non-bulbar
Vital Capacity
< 71%
> 71%
ALS-FRS-R
< 37
> 37
Time to clinic
< 13
> 13
Median Survival
P value
31
30
0.6192
26
34
0.0054*
25
36
<0.0001*
23
36
<0.0001*
24
37
<0.0001*
Covariate
Hazard
Ratio
95% CI
p value
Time to clinic <
13 months
Age > 59 yrs
1.8140
1.3832 to 2.3791
<0.0001
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




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
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, high
calorie
- High
carbohydrate,
high calorie
22
3
mos
Wt stabilized
ALS-FRS progressed
- High fat, high
calorie (Oxepa)
- High carb, high
calorie (Jevity
1.5)
- Control (Jevity)
8
Wills, et al
16
High drop out rate with High
carb/high calorie
9
7
4
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