1. Managing a patient with ALS (Amyotrophic Lateral Sclerosis)
Presented by: John Sugrue

2. Objectives Provide an example of a patient with ALS
Discuss pathophysiology of ALS and its progression
Identify proven drug therapy as well as some potential drugs to aid in symptom management
Analyze the example patient’s medication list to optimize therapy

3. Patient Case
JD is a 56 year old female presenting to the ED with increasing lethargy and altered mental status.
Past Medical History:
ALS
DVT PE
s/p IVC filter
Dyslipidemia
Iron-deficiency anemia
Chronic lymphedema
GERD
Nephrolithiasis
Single kidney
Recurrent UTI

4. Patient Case
Social History: lives at home, VNA comes to house. No smoking, alcohol, or other drug abuse.
Family History: Non-contributory
Review of Systems (pertinent positives):
GI – positive for abdominal pain
MS – positive for muscle pain from spasms in lower limb.
Neuro – altered mental status
Allergies: Oxycodone, Percocet, codeine

5. Patient Case Home Medications Baclofen 20 mg 2 tablets PO AM, 3 PO PM
Docusate 100 mg capsule PO BID PRN
Mirtazapine 15 mg tablet PO at bedtime
Morphine 30 mg tablet PO TID
Nystatin topical powder, apply topically three times daily to affected areas

6. Patient Case Medications continued: Omeprazole 40 mg capsule PO QD
Riluzole 50 mg tablet PO Q12H
Senna 8.6 mg 2 tablets PO QD PRN
Simvastatin 20 mg tablet PO at bedtime
Sucralfate 1 g tablet PO TID before meals and bedtime
Venlafaxine 100 mg tablet PO TID

7. Patient Case
Vitals upon admission T – 97.6 F HR – 92 RR – 22 BP – 122/71 O2 sat- 100%
Height – 156 cm
Weight – 84.4 kg
Pertinent Labs
WBC’s urine - >182/HPF
RBC’s urine – 52/ HPF
Chem 7 WNL

8. About ALS Often developed between ages of 40-75.
Affected Patients: 60% - male, 93% - Caucasian.
Approximately 6,000 new diagnoses every year in the US
Estimated 20,000 people living with ALS in US.
Life expectancy once diagnosed is an average of 3 years
10% live with disease for 10 years
5% live with disease for 20 years
Military veterans are twice as likely to develop ALS
What is ALS? [Internet]. Washington DC: The ALS Association; 2016 [cited 2016 Dec 1] Available from:

9. Pathophysiology Progressive degeneration of motor neurons
Motor neurons are then unable to send a signal to voluntary muscles to contract
Muscles atrophy and harden (sclerosis)
Image from:
What is ALS? [Internet]. Washington DC: The ALS Association; 2016 [cited 2016 Dec 1] Available from:

10. Progression Gradual onset Progressive painless muscle weakness
Hands
Voice
Swallowing
Uncontrolled expression of emotion (laughing/crying)
Dyspnea

11. Rilutek® (riluzole)
Only drug FDA approved to prolong life/slow disease progression in patients with ALS.
MOA: unknown, however there are some hypotheses
Inhibition of glutamate release
Inactivates sodium gated channels
Interference with excitatory amino acid receptors
Major side effect = fatigue and nausea.
HTN, dizziness, ↑ LFT’s, ↓ lung function
Image from:
Lexicomp. Rilizole. [online] 1 December 2016

12. Rilutek® (riluzole) Dosed at 50 mg tablet by mouth twice daily
Considerations
Severe neutropenia has been reported within the first 2 months of treatment
May cause hepatic injury
Major CYP1A2 substrate
When taking riluzole with high fat meals, the level in the blood is reduced by about half.
Lexicomp. Rilizole. [online] 1 December 2016

13. Clinical Trials
A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.
Purpose: to evaluate the efficacy and safety of riluzole in patients with ALS.
Setting: Hôpital de la Pitié-Salpêtrière, Paris, France,
Methods: double blind, placebo-controlled trial in 155 patients with ALS
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group [abstract]. N. Engl. J. Med March; 330(9):

14. Clinical Trials
Primary Endpoints: survival and rates of change in functional status
Results: after 12 months, 58% still alive in placebo, 74% still alive in riluzole group (p=0.014). Deterioration of muscles was significantly slower in riluzole group when compared to placebo group (p=0.046).
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group [abstract]. N. Engl. J. Med March; 330(9):

15. Clinical Trials Set the bar for studies to come
The US guidelines mention 4 class I studies supporting the safety and efficacy of riluzole for its indication of slowing disease progression of ALS and increasing survival time.
Miller R.G., Jackson C.E., Kasarskis E.J., et al. The care of the patient with amyotrophic lateral sclerosis. American academy of Neurology. 2009; 73:1218–1226.

16. Symptoms to be treated PBA (Pseudobulbar Affect) Thick mucus
Sialorrhea
Muscle spasticity
Cramps
Insomnia
Fatigue

17. PBA (Pseudobulbar Affect)
Definition: Emotional lability in the form of laughter, crying, or yawning at inappropriate times
Very common in ALS patients (around 50%)
Medications
Combination quinidine and dextromethorphan (Nuedexta®)
20 mg DM/10 mg quinidine once daily for 7 days then increase to BID
Amitriptyline 25 mg once daily (can go up to 100mg/day as tolerated)
Fluvoxamine 50 mg once daily
Citalopram not to exceed 40 mg/day.
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

18. Thick mucus
Can complicate breathing by getting stuck in respiratory tract
Medications
N-acetylcysteine mg by mouth TID
Any combination of the following:
Beta antagonist and nebulizer w/ saline (carvedilol, propranolol etc…)
Anticholinergic bronchodilator (tiotropium etc…)
Furosemide
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

19. Sialorrhea (excessive drooling)
Medications
Amitriptyline 10 mg tablet by mouth TID
Atropine 0.5-1% sublingual drops, one drop 3-4 times daily
Scopolamine 1.5 mg transdermal patch every 3 days
Careful with anticholinergics in older patients
Botulinum toxin injection
Should be reserved for refractory sialorrhea
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

20. Muscle Spasms
Physical therapy is the most important aspect of treatment
Medications
Antispastic medications such as baclofen or tizanidine
No clinical trials with ALS patients but has been used
Intrathecal baclofen
In cases of severe/refractory spasticity
Gabapentin, memantine, dantrolene, tetrazepam, diazepam.
Have been used but no testing in ALS patients has been conducted.
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

21. Cramps Can be debilitating in patients with ALS, especially at night.
Medications
Levetiracetam
Quinine sulfate
Physical therapy can help tremendously with this issue.
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

22. Insomnia
Patients can have trouble, especially as symptoms progress to leg cramps and more associated pain.
Medications
Amitriptyline
Mirtazapine
Zolpidem
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

23. Fatigue Most common side effect of riluzole
Discussion about discontinuing medication if fatigue is too devastating
QOL vs. prolonging life
Two trials showed that modafinil was effective in increasing patients energy
Long term effects on ALS patients has yet to studied.
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.

24. Stem cells
Stem cell research is being conducted with the goal of protecting the affected motor neurons
The theory is that these stem cells will produce growth factors or other molecules to protect motor neurons in the spinal cord.
Stem cell treatment is still in the early phases of clinical trials but stem cells from ALS patients are being used for research purposes.
Stem Cells [Internet]. Washington DC: The ALS Association; 2016 [cited 2016 Dec 1] Available from:

25. Revisiting JD
Patient was suspected to have a UTI due to WBC’s and blood in urine
Was treated with a 4 day course of Zosyn, clinically improved and altered mental status returned to baseline

26. Revisiting JD’s Medications
Baclofen
Docusate
Mirtazapine
Morphine
Nystatin
Omeprazole
Riluzole
Senna
Simvastatin
Sucralfate
Venlafaxine

27. References
What is ALS? [Internet]. Washington DC: The ALS Association; 2016 [cited 2016 Dec 1] Available from:
Lexicomp. Rilizole. [online] 1 December 2016
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group [abstract]. N. Engl. J. Med March; 330(9):
Miller R.G., Jackson C.E., Kasarskis E.J., et al. The care of the patient with amyotrophic lateral sclerosis. American academy of Neurology. 2009; 73:1218–1226.
Anderson P, Abrahams S, Borasio G, et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis. European Journal of Neurology. 2012; 19: 360–375.
Stem Cells [Internet]. Washington DC: The ALS Association; 2016 [cited 2016 Dec 1] Available from: