clinical

1. D R . S A C H I N A D U K I A
Management of MND as per
guidelines

2. INTRODUCTION
⚫ Neuro-degenerative disorder which affects the motor neurons in the motor
cortex, spinal cord and brainstem
⚫ Development of clinical weakness till about 30% AHC are lost
⚫ Rostral to caudal progression is faster than otherwise.
⚫ There can be transitory improvement, plateau or sudden worsening.

3. INTRODUCTION
⚫ mean 5 year survival rate is around 22%
⚫ mean 10 year survival rate is around 10%
⚫ Most robust poor prognostic factors are
 Older age at onset
 Bulbar onset
 Short interval between onset and clinical diagnosis
 Rapid progression rates
 Low BMI
 FTD-ALS presentation
 Rapid decline in respiratory function

4. COMPREHENSIVE MANAGEMENT OF
PATIENT WITH ALS
⚫ Presentation of the diagnosis
⚫ Specific pharmacotherapy
⚫ Symptomatic treatment
⚫ Multi-disciplinary team approach
⚫ Physical rehabilitation
⚫ Speech and communication management
⚫ Nutritional care
⚫ Respiratory care
⚫ Home and hospice care

5. Breaking the news
⚫ No RCTs available to conclude ideal method.
⚫ Following methods can be considered:
 Compassionate yet informative manner
 Allow adequate time
 Patient should not be alone
 Arrange second appointment for queries and after thoughts
 Provide information about latest research, clinical trials
 Advanced directives and issues about terminal care

6. SPECIFIC PHARMACOTHERAPY
⚫ Riluzole: antiglutamate agent
⚫ Approved by U.S FDA in 1996
⚫ A Cochrane meta-analysis : 100mg/d results in 9% increase in probability of
survival for 1 year and prolongs median survival by 2-3 months when taken for
18 months(Miller et al, 2012)

7. ⚫ riluzole 50 mg BID to prolong survival for those with definite or probable ALS
less than 5 years duration, with forced vital capacity (FVC) 60%, and without
tracheostomy (Level A).
⚫ modest beneficial effect in slowing disease progression (prolonged survival of
2–3 months) based on 4 Class I trials.
⚫ should be offered to slow disease progression in patients with ALS (Level A).

8. ⚫ Edaravone was approved in May 2015 for the treatment of ALS by FDA
⚫ IV Edaravone 60 mg over 60 minutes
 Treatment is started with daily infusion for 14 days, followed by 14 days off
treatment.
 Subsequent daily edaravone 60 mg infusions on 10 days within a 14 day
period, followed by 14 days off treatment.

9. SYMPTOMATIC MANAGEMENT
⚫ What are the most effective treatments for sialorrhea?
⚫ Agents like
 Hyoscyamine sulphate
 Diphenhydramine
 Scopolamine patch
 Glycopyrrolate
 Atropine
 TCA
⚫ In medically refractory sialorrhea,
⚫ Botox should be considered (Level B)
⚫ low-dose radiation therapy to salivary glands may be considered (Class I, Level
C).

10. ⚫ For pseudobulbar affect
⚫ combination of Dexmethorphan / Quinidine sulphate is probably effective (1
Class I study)
⚫ Pending FDA approval (Level B).

11. ⚫ To reduce fatigue?
⚫ Agents:
 Pyridostigmine
 Antidepressants
 Methylphenidate
 Amantadine
 Modafinil
⚫ There are no controlled studies of pharmacologic agents relieving fatigue in
ALS.
⚫ Riluzole possibly causes fatigue in some patients (2 Class III studies).

12. ⚫ Other measures
 Energy conservation
 Work modification
 BiPAP if sleep study is abnormal.

13. ⚫ To reduce cramps?
⚫ Agents
 Quinine sulphate
 Baclofen
 Vitamin E
 Clonazapam
⚫ Other therapies
 Massage
 Physical therapy

14. ⚫ Studies of gabapentin, vitamin E, and riluzole for treating cramps were all
negative (Class III).
⚫ There are safety concerns about quinine.
⚫ There are insufficient data to support or refute any specific intervention for the
treatment of cramps in ALS (Level U).

15. ⚫ What interventions reduce spasticity?
⚫ Agents
 Baclofen
 Tizanidine
 Dantrolene Sodium
 Diazepam
⚫ Other therapies
 Physical therapy
 Botulinum toxin

16. ⚫ Evidence is insufficient to recommend exercise or medication for treating
spasticity in ALS (Class III).
⚫ There are insufficient data to support or refute exercise or medication for
treating spasticity in ALS (Level U).

17. ⚫ To reduce depression?
⚫ Agents:
 TCAs
 SSRIs
 Venlafaxine
 Mirtazipine
 Bupropion
⚫ Other therapies
 Counselling
 Support group meetings
⚫ No controlled trials available

18. ⚫ To reduce insomnia?
⚫ Agents
 Zolpidem
 Lorazepam
 Opioids
 TCAs
⚫ Other therapies
 Air mattresses
 NPPV
⚫ No clinical trials available

19. COGNITIVE AND BEHAVIOURAL
IMPAIRMENT
⚫ Specific ALS phenotypes include
 Pure motor degeneration (ALS)
 ALS with cognitive impairment (ALSci)
 ALS with behavioral impairment (ALSbi)
 ALS with a dementia meeting the Neary criteria for frontotemporal dementia
(FTD) (ALS-FTD).

20. ⚫ A significant proportion of patients with ALS demonstrate cognitive
impairment and some have dementia (2 Class II, multiple Class III studies).
⚫ Neither behavioral impairment in ALS nor the natural progression of cognitive
or behavioral impairments has been adequately studied.
⚫ Screening for cognitive and behavioral impairment should be considered in
patients with ALS (Level B).

21. SPEECH AND COMMUNICATION MANAGEMENT
⚫ Speech pathologists should assess speech and communication immediately
after establishing diagnosis.
⚫ Non verbal techniques like
 gestures,
 body language alphabet and picture boards,
 voice synthesizer can be used.

22. PHYSICAL REHABILITATION
⚫ Objective is to improve the ability to carry out activities of daily living as far as
possible without causing physical or emotional strain.
⚫ Exercises to enhance strength, endurance and range of motion, occupational
therapy.
⚫ Adaptive and assistive devices like walkers, wheelchairs, splints and collars.
⚫ Modification of home environment.

23. NUTRITION MANAGEMENT
⚫ In ALS, factors that restrict adequate nutrition develop insidiously and
progressively worsen.
⚫ functional consequences are choking, aspiration, weight loss, and dehydration.
⚫ Strategies to maintain oral nutritional intake consist of altering food
consistency and using nutritional supplements.
⚫ (PEG) or radiologically inserted device [RIG]) - an alternative route for
delivering nutrition
⚫ PEG does not eliminate oral feeding but offers a convenient method for
administering medication and fluid and stabilizing weight.

25. ⚫ What is the efficacy of vitamin and nutritional supplements on prolonging
survival or quality of life?
⚫ Creatine should not be given as treatment for ALS because it is not effective in
slowing disease progression (Level A).
⚫ High-dose vitamin E should not be considered as treatment for ALS (Level B),
while the equivocal evidence regarding low-dose vitamin E permits no
recommendation (Level U).

26. RESPIRATORY MANAGEMENT
⚫ The diagnosis and management of respiratory insufficiency is critical because
most deaths from ALS are due to respiratory failure.

28. ⚫ What are the optimal pulmonary tests to detect respiratory insufficiency?
⚫ Nocturnal oximetry may be considered to detect hypoventilation (regardless of the
FVC) (Level C).
⚫ Supine FVC and MIP may be considered useful in routine respiratory monitoring,
in addition to the erect FVC (Level C).
⚫ Sniff nasal pressure may be considered to detect hypercapnia and nocturnal
hypoxemia (Level C)

29. ⚫ Does NIV improve respiratory function or increase survival?
⚫ NIV is probably effective in prolonging survival (1 Class I, 3 Class III studies)
and in slowing the rate of FVC decline (1 Class I, 1 Class III study).
⚫ NIV should be considered to treat respiratory insufficiency in ALS, both to
lengthen survival and to slow the rate of FVC decline (Level B).

30. ⚫ What is the efficacy of targeted respiratory interventions for clearing secretions
⚫ Expiratory respiratory muscle weakness can lead to ineffective cough, retained
upper airway secretions, and pulmonary infection. PCEFs greater than 160
L/min are needed to clear secretions and clinicians recommend assistive
devices when the PCEF falls below 270 L/min (Class III).
⚫ Mechanical insufflation/exsufflation (MIE) increased the PCEF by 17% in
healthy controls, 26% in bulbar patients, and 28% in nonbulbar patients (Class
III).
⚫ Manually assisted cough increased flow by 11% in bulbar and 13% in nonbulbar
patients.

31. HOME CARE AND HOSPICE CARE FOR TERMINALLY ILL
⚫ When the patient is terminally ill, home or hospice care is required.
(Mitsumoto et al, 2005)
⚫ Close collaboration between patients, care givers, nurses and the ALS team
⚫ maintain independence and dignity of the patient in the terminal stages.

32. References
⚫ Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of
the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory
therapies (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2009; 73:1218.
⚫ FDA approves drug to treat ALS. https://www.fda.gov/NewsEvents
/Newsroom/PressAnnouncements/ucm557102.htm
⚫ Hardiman O, van den Berg LH. Edaravone: a new treatment for ALS on the
horizon? Lancet Neurol 2017; 16:490.

33. THANK YOU