1. Amyotrophic lateral sclerosis
By: Catherine Fayer
EXS486

2. What is ALS?
Progressive, neuromuscular disease characterized by the upper and lower motor nerve cell degeneration
Upper neurons located in brain
Controls eye movement, tongue movement, chewing, swallowing, and speaking.
Lower motor neurons are located in the spinal cord and control voluntary movement of the skeletal muscle
Affected neurons prevent skeletal muscle innervation
Causes muscle atrophy

3. What is the Role of the nerve fibers?
Neurons are unable to send electrical impulses to tell the muscle to move
Atrophied muscle can not be revived because of the lack of signals

4. Protein Aggregation
-Degenerating motor neurons and surrounding oligodendrocytes
-Lewy body-like hyaline inclusions or skein-like inclusions
-Bunina bodies

5. Role of SOD1 cu-zn superoxide dismutase
- First known involvement of protein aggregation (exact mechanisms still unclear)
-Leads to misfolded proteins (protein aggregation)
-Decrease in activity in ALS patients
-Gains a toxic property ;indirect cause
-Binds copper and zinc ions to metabolize hydrogen peroxide and oxygen and prevent superoxide radical damage

6. Genetics of ALS Inherited: only 5-10% ALS cases
 C9orf72 gene responsible for 30-40% familial cases
SOD1 gene mutations 20%
Mostly autosomal dominant pattern
-Only need one mutated gene to pass on disease (one parent)
Rare: Autosomal recessive pattern
-Each parent has a copy of mutated gene
Genetics Home Reference

7. Progression of ALS
*Death within 2-5 years of onset……. bulbar-onset vs. the spinal-onset
Early:
-Muscles begin atrophy
-Single body region symptoms
-Muscle twitches ,cramping/stiffness
Middle
-Symptoms more wide spread ; paralyzed muscles
-difficulty swallowing and breathing
Late
-Limited Mobility: muscle paralysis
-Slurred Speech
- Cannot chew/swallow

8. Symptoms of ALS Involuntary muscle twitch Cramps Muscle spasticity
Muscle weakness
Muscle atrophy
Joint contractures (shoulders, knees, ankles)
Slurred speech
Shortness of breath
Difficulty chewing and swallowing

9. Diagnosis of ALS
Neurologist physical examination :muscle strength, reflexes, coordination, and sensation
Electromyography (EMG)
Nerve Conduction Velocities (NCV)
Additional testing:
Spinal tap
Muscle/nerve biopsy
Cervical Spine MRI

10. Effect of ALS on Exercise Response
- Higher resting energy expenditure
-Myth: excessive exercise accelerates weakness due to overuse (no evidence)
-Normal increase oxygen consumption and heart rate during 50% VO2 tests
-Normal neural and muscular adaptations during strength training

11. Management and Meds NO CURE TO ALS -Rilutek (riluzole)
-Slows rate of progression
-preserves nerves from glutamate toxicity
Does not reverse nerve damage
- Reduce spasticity: baclofen or diazepam
-Reduce Pain: Gabapentin
- Non-invasive positive pressure ventilation (NIV)

12. Case Study
Patient Details: 58 years old female, 54 kg, 160cm,Stage I spinal-onset ALS: Moderate weakness in groups of muscles such as her arms, wrists, and legs. She has recently lost 2 kg weight loss (about 4.5lbs).She used to be active by gardening and performing house work, but she has been sedentary the past 3 months due to fatigue. Her FBG = 90 mg/dl; HDL = 30 mg/dl; LDL = 110 mg/dl . She does not have any family history of disease and she has never smoked a day in her life.

13. Risk Stratification
Age: < Obesity: No +0 Family History: +0 Smoking: No + 0 Dyslipidemia: > 130 mg/dl + 0 Sedentary Lifestyle: Yes +1 Prediabetes: > 100mg/dl +0 High HDL: No +0 Risk Group: Moderate (2 risk factors) Physician consent Goals: Preserve functioning muscles, prevent muscle stiffening and spasms, improve quality of life Special Considerations: Exercises must be supervised for risk of falling. Exercise cannot be too strenuous because it can speed up progression of disease (must be gradual progression)

14. Exercise Testing
-TQNE(Tufts Quantitative Neuromuscular Exam )qualitative test to determine stage of ALS
-tests pulmonary function, oropharyngeal, timed motor activities, and maximal isometric strength.
-YMCA submaximal ergometer bike test
obtain two heart rates between 110 and 150 bpm at RPM 50
-Rockport Walking Test
-1-mile walk
-Six-minute walk test (6MWT)
-more progressive symptoms of ALS-distance in 6 mins
-nchpad

15. Exercise Prescription
Frequency
Intensity
Time
Type
Cardiovascular
3 days per week
50% of VO2max
(moderate)
15-30 mins (can be performed in 10 minute bouts)
Swimming, walking, ergonomic bike
Resistance
2-3 days per week
Low-Moderate
(gradual resistance increase)
10-12 reps
Start at 40% 1RM
1 -3 sets (progression)
Isometric or dynamic
-low weight DB exercises
Balance/Flexibility
Most days of the week
Moderate
30 mins
Range of Motion( active and passive)

16. Conclusion
ALS is progressive neurodegenerative disease that affects thousands of us every day. There must be further research on this disease to find a solution rather than medications that only temporarily prolong life. For patients who are diagnosed, moderate cardiovascular and muscular strength exercises can improve quality of life by preserving muscle . Flexibility is another essential exercise prescription which prevents muscle spasm and stiffening.
WE NEED MORE RESEARCH

17. References
ALS. (n.d.). Retrieved October 30, 2015, from
Amyotrophic Lateral Sclerosis (ALS): Fact Sheet. (n.d.). Retrieved October 27, 2015, from
Amyotrophic Lateral Sclerosis (ALS) : NCHPAD - Building Inclusive Communities. (n.d.). Retrieved October 27, 2015, from
Amyotrophic lateral sclerosis. (n.d.). Retrieved October 28, 2015, from sclerosis
Assistance in Stages of ALS Amyotrophic Lateral Sclerosis. (n.d.). Retrieved October 28, 2015, from
Blokhuis, A. M., Groen, E. J. N., Koppers, M., van den Berg, L. H., & Pasterkamp, R. J. (2013). Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathologica, 125(6), 777–794.
Fabian H. Rossi, Maria Clara Franco and Alvaro G. Estevez (2013). Pathophysiology of Amyotrophic Lateral Sclerosis, Current Advances in Amyotrophic Lateral Sclerosis, Prof. Alvaro Estévez (Ed.), ISBN: , InTech, DOI: / Available from: amyotrophic-lateral-sclerosis
Lopes de Almeida, J., Silvestre, R., Pinto, A., & De Carvalho, M. (2012). Amyotrophic Lateral Sclerosis. SpringerReference, 33, doi: /s