Weight and Muscle Mass Loss Associated with Acute Disease Can Be Reversed with Appropriate Nutrition Therapy and Exercise in a Patient with Amyotrophic Lateral Sclerosis

Abstract

Nutritional interventions targeting weight loss are useful for the treatment of amyotrophic lateral sclerosis (ALS). However, the changes in body composition after nutritional intervention remain unclear. We herein present a patient with ALS who experienced an increased weight and muscle mass owing to nutritional therapy and physical exercise. An 86-year-old man presented with dysphagia and dysarthria. The patient was diagnosed with bulbar-type ALS. As weight loss progressed, a gastrostomy was performed. After 21 months of disease onset, gastrointestinal bleeding due to a bumper ulcer led to further weight loss (from 40.2 kg to 36.8 kg). The patient experienced difficulty walking and ingesting food orally. Although the total daily energy expenditure (TDEE) was estimated to be 1,122 kcal/day, an intake of 1,500 kcal/day beyond the calculated TDEE was administered. The patient continued to perform daily voluntary exercises in addition to his usual rehabilitation. After 5 months, his weight increased from 36.8 kg to 40.4 kg. Muscle mass increased from 25.1 kg to 30.1 kg, as measured using a multifrequency bioelectrical impedance device. Muscle strength improved from 8.5/10.0 kg to 15.0/18.0 kg in grip strength and from 15.2 kPa to 20.4 kPa in tongue pressure. The patient's physical and swallowing functions also improved. In patients with ALS, a decreased body weight and muscle mass due to acute disease may be improved by appropriate nutritional therapy and physical exercise.

Introduction

Weight loss affects the prognosis of amyotrophic lateral sclerosis (ALS) (1). Nutritional intervention targeting weight loss is a well-established treatment for ALS (1,2). Muscle and fat wasting during the disease course may serve as prognostic factors and provide guidance for nutritional management of patients with ALS (3). However, changes in body composition, including muscle mass and fat tissue, after nutritional therapy remain unclear.

We herein present a patient with ALS who recovered weight and muscle mass with appropriate nutritional therapy and exercise.

Case Report

An 86-year-old man presented to our hospital with dysphagia and dysarthria. Twelve months after symptom onset, tongue atrophy and fasciculations were observed. The flexor muscles of the neck exhibited mild weakness. He had upper motor neuron signs in the brainstem and cervical spinal regions and lower motor neuron signs in the brainstem, cervical spine, and lumbar spinal regions. Needle electromyography of the left first interossei dorsalis muscle (1st IOD), quadriceps, and tivialis anterior (TA) showed a high amplitude, and interference waves of the left upper trapezius, 1st IOD, quadriceps, and TA showed decreased amplitudes, thus reflecting neurogenic changes. He was diagnosed with bulbar-type laboratory-supported probable ALS, according to the updated Awaji criteria (4). His height was 160.8 cm and the weight at diagnosis of ALS was 44.8 kg. The ALS Functional Rating Scale-Revised (ALSFRS-R) score was 37. Dysphagia was classified as level 5 on the Food Intake LEVEL Scale (FILS; easy-to-swallow food is orally ingested in three meals. No alternative nutrition was given) (5). The patient's weight loss gradually progressed. Sixteen months after the ALS diagnosis, videofluoroscopic examination of swallowing (VF) revealed pharyngeal residue, and his weight decreased to 40.9 kg. A gastrostomy was performed while the patient was still able to ingest food. At that time, his dysphagia was classified as level 5 on the FILS (easy-to-swallow food is orally ingested in one or two meals, but alternative nutrition is also provided). After 21 months after disease onset, he developed gastrointestinal bleeding due to a contact bumper ulcer (6), and laboratory tests revealed anemia (hemoglobin 8.0 g/dL). His weight decreased from 40.2 kg to 36.8 kg over the course of a month. Despite the improvement in his general condition, he experienced difficulty walking and consuming food orally. At that time, his ability to swallow was classified as level 2 on the FILS (swallowing training without food was performed).

The patient was then transferred to a rehabilitation hospital. The total daily energy expenditure (TDEE) for this patient was estimated at 1,122 kcal/day using the following equation: (1.67×Harris-Benedict equation)＋(11.8×ALSFRS-R score)-680 (7). Nutritional therapy commenced with an intake of 1,500 kcal/day beyond the calculated TDEE, administered through a percutaneous endoscopic gastrostomy (PEG) tube at the patient's request. The enteral nutrition at 1,500 kcal/day contained carbohydrates (62%), proteins (18%), and fat (20%). Oral intake at the enjoyment level was continued. Furthermore, the patient continued to perform daily voluntary physical exercise for approximately 30 min/day in addition to daily rehabilitation, including swallowing training. He performed gait training and mild muscle strengthening exercises of his extremities using weights as voluntary physical exercise, which did not lead to fatigue. The patient continued these exercises daily after discharge. After 5 months of intervention, his body weight increased from 36.8 to 40.4 kg (Table). Furthermore, his muscle mass increased from 25.1 kg to 30.1 kg, as determined using the multifrequency bioelectrical impedance (BIA) device (InBody S10; InBody, Seoul, Korea). The muscle mass of the upper and lower extremities and trunk increased, whereas the fat mass decreased. His muscle strength improved from 8.5/10.0 kg to 15.0/18.0 kg in grip strength and from 15.2 kPa to 20.4 kPa in tongue pressure, determined using a balloon-type device (TPM-01; JMS, Hiroshima, Japan). The vital capacity improved from 72.5% to 80.2%. His physical function improved, from requiring a wheelchair to walking with a cane. Regarding his swallowing function, although pharyngeal contraction was weak, relaxation of the upper esophageal sphincter (UES) improved in the VF (Fig. 1). The pharyngeal bolus passage improved, and pharyngeal residues were reduced. High-resolution manometry (HRM) after therapeutic interventions showed significantly lower pharyngeal contractility than that of older adult patients with sarcopenic dysphagia (8), while the UES opened partially. At that time, his ability to swallow was classified as level 4 on the FILS (swallowing training using a small quantity of food was performed). After 18 months of nutritional and rehabilitation intervention, the patient's weight and muscle mass were maintained with a nutritional intake of 1,500 kcal/day via PEG and physical exercise. The patient's clinical course is shown in Fig. 2.

Table.

Comparison of Clinical Parameters before and after Nutritional and Rehabilitation Intervention.

	At diagnosis	Before intervention	5 months after intervention	18 months after intervention
Body weight (kg)	44.8	36.8	40.4	41.0
Muscle mass (kg)
General	n/a	25.6	30.1	31.4
Upper limbs	n/a	1.6	2.1	2.8
Trunk	n/a	11.1	12.6	14.6
Lower limbs	n/a	8.9	11.4	10.5
Fat mass (kg) [%]	n/a	9.4 [25.5]	8.4 [20.8]	7.6 [18.6]
Grip (kg)	n/a	8.5/10.0	15.0/18.0	17.6/20.6
Tongue pressure (kPa)	n/a	15.2	20.4	n/a
ALSFRS-R (points)	37	28	33	33
%VC	96.5%	72.5%	80.2%	71.0%
Physical function	Walking without cane	Wheelchair use	Walking with cane	Walking with cane
VF
Pharyngeal residues	moderate	severe	moderate	moderate
Aspiration	-	+	-	-
FILS	7	2	4	4
Blood test
Total protein (g/dL)	6.8	5.4	6.8	7.8
Albumin (g/dL)	3.8	2.8	3.6	3.8
Creatinine (mg/dL)	0.65	0.43	0.51	0.56
Total cholesterol (mg/dL)	148	n/a	147	156
Manometric study
VPCI (mmHg·cm·s)	n/a	n/a	12.7±3.7	n/a
MHPCI (mmHg·cm·s)	n/a	n/a	24.7±6.2	n/a
UES relaxation duration (ms)	n/a	n/a	227±46	n/a
UES nadir pressure (mmHg)	n/a	n/a	-0.9±5.4	n/a

ALS: amyotrophic lateral sclerosis, ALSFRS-R: ALS Functional Rating Scale-Revised, FILS: Food Intake LEVEL Scale, MHPCI: mesopharyngeal contractile integral, n/a: not availavle, UES: upper esophageal sphincter, VC: vital capacity, VF: videofluoroscopic examination of swallowing, VPCI: velopharyngeal contractile integral

Figure 1.

VF before and after nutritional and rehabilitation intervention. a) VF before treatment intervention; the bolus did not pass through the UES. b) Post-therapeutic VF; the bolus passed through the UES partially during swallowing (arrowhead). VF: videoendoscopic examination of swallowing, UES: upper esophageal sphincter

Figure 2.

The clinical course regarding nutrition and rehabilitation intervention. The patient experienced an increase in the ALSFRS-R scores, gained weight, and demonstrated an improved swallowing function following therapeutic intervention (nutrition therapy and rehabilitation). ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, FILS: Food Intake LEVEL Scale, PEG: percutaneous endoscopic gastrostomy

Discussion

To the best of our knowledge, this is the first report to use BIA to demonstrate that nutritional therapy and physical exercise can increase body weight and skeletal muscle mass in patients with ALS. In addition, the muscle strength, including grip strength and tongue pressure all improved.

The most important findings were as follows: 1) a decreased weight due to acute disease can be increased by nutritional therapy and physical exercise, and 2) an increased weight can mainly be attributed to an increased skeletal muscle mass, not fatty tissue. In this case, the patient lost weight because of gastrointestinal bleeding and a lack of energy intake because of fasting. However, the patient gained weight within approximately 5 months with appropriate nutritional therapy and rehabilitation. The patient's physical function and muscle strength, including grip strength, improved. Increased trunk muscle mass and improved respiratory function were also observed. Interestingly, the fat mass was reduced after therapeutic intervention, which may be attributed to the fact that exercise was performed in addition to daily rehabilitation.

Important therapeutic interventions may have been sufficient for nutrition beyond TDEE and physical exercises, including resistance training. A high-calorie diet, including lipids or carbohydrates, increased the patient's body weight by 0.6-0.9 kg/month (9). The usefulness of rehabilitation, including resistance exercises, on the progression of ALS has been reported (10,11). However, no study has investigated the components of increased body weight associated with nutritional therapy and rehabilitation. Evaluating the body composition using BIA may be useful for determining the effects of therapeutic interventions and predicting prognosis in patients with ALS.

Interestingly, the swallowing function also improved in this patient. Tongue pressure, which reflects the strength of the swallowing-related muscles, increased and pharyngeal residue decreased in the VF examination. Tongue pressure is useful for evaluating swallowing function in ALS (12,13). Posttherapeutic VF showed an improved opening of the UES. HRM revealed partial UES opening and significantly decreased pharyngeal contraction. The UES function improved, thus reflecting the improvement in suprahyoid muscle strength due to therapeutic intervention.

Nevertheless, these findings should be cautiously interpreted. Moreover, the appropriate nutritional components for increasing weight and muscle mass, in combination with physical exercise, remain unclear. Thus, further research is required to verify the nutrient components that are effective in combination with rehabilitation.

In summary, in patients with ALS, a decreased body weight due to acute disease onset may be improved by nutritional therapy beyond TDEE and physical exercise. Measuring the muscle mass using BIA may be beneficial for assessing the effects of therapeutic interventions. Further studies are needed to clarify the relationship between the changes in body composition associated with these interventions and the prognosis.

The authors state that they have no Conflict of Interest (COI).

Financial Support

This work was supported by JSPS KAKENHI (Grant No. 21K17471).