The document discusses predictors of tolerance to non-invasive ventilation (NIV) and survival in patients with amyotrophic lateral sclerosis (ALS). It finds that younger age of onset, limb-onset symptoms rather than bulbar symptoms, and earlier use of NIV may predict better tolerance of NIV and longer survival. The document also suggests that multidisciplinary care in specialized ALS clinics may improve prognosis compared to general neurologist care. Organizing integrated care across reference centers and local providers may help improve outcomes for ALS patients.

1. ALS: Tolerance and survival predictors Cáceres, 10 de Noviembre de 2007 Dr. Joan Escarrabill Hospital Universitari de Bellvitge L’Hospitalet (Barcelona) [email_address]

3. ALS: some figures Forbes RB et al. J Neurol Neurosurg Psychiatry 2004;75:1753-55 Kimura F et al. Neurology 2006;66:265-7 Mean age at onset 65 yrs From onset to diagnosis 15 months Czaplinski A et al. J Neurol 2006;253:1428-36 Diagnostic Overall median survival 2-4 yrs Five years survival 11% Survival > 8 years 4% Survival

4. Predictors PEG Care organization Bulbar involvement at onset NIV Secretions magement Nihilism Autonomy Management of acute problems Age at onset

6. Amyotrophic lateral sclerosis Onset of symptoms First visit Onset NIV Medical delay Unclear first symptom Precocious NIV Palliative End-of-life NIV Studies are difficult to compare

7. Amyotrophic lateral sclerosis Onset of symptoms First visit Onset NIV Medical delay Unclear first symptom Palliative End-of-life NIV Precocious NIV

8. Amyotrophic lateral sclerosis Onset of symptoms First visit Onset NIV Medical delay Unclear first symptom Precocious NIV Palliative End-of-life NIV

10. Neurology 2005;64:38-43 Symptom duration at baseline visit was a significant predictor of survival Shorter duration = Higher mortality Symptom duration at first visit related to rate of disease progression ALSFRS-R Physical function in daily living activities Salivation Swallowing 4 3 2 1 0 4 3 2 1 0 Cedarbaum JM. J Neurol Sci 1999;169:13-21

11. J Neurol Neurosurg Psychiatry 2004;75:1753-55 Scottish ALS Register n=1226 2.4 months Medical nihilism ? Riluzole & PEG use increases Patient autonomy Less aggressive therapy

12. ALS: Acute chest infection Servera E. J Neurol Sci 2003;209:111-3 65 yrs old man Daytime Mouth piece Nasal mask for nocturnal use

13. Secretions management MI-E Ventilador+30 +TAT Ventilador+TAT Air stacking+TAT TAT SPON + mot SPON 1100 1000 900 800 700 600 500 400 300 200 100 0 ٭ ٭ ٭ ٭ ٭ † † † † ‡ ‡ ‡ • PCF l/mn Courtesy of Cristina Senent MD (H. Sant Joan - Alacant) & Jesus González MD (Hôpital Pitié-Salpetière - Paris)

14. Bulbar impairment Bulbar Non-Bulbar Bourke SC. Lancet Neurol 2006;5:140-7

15. Survival in ALS patients with bulbar involvement Farrero et al. Chest 2007;127:2132-8 NIV Tolerance NIV intolerance NIV Tolerance NIV intolerance NIV Tolerance NIV intolerance Hypercapnia Normocapnia

17. Survival on HMV Laub M & Midgren B. Respir Med 2007;101:1074-8 n=1526 ALS

18. Indication of NIV Melo J. J Neurol Sci 1999;169:114-7 n=2357 patients 15% on NIV

19. Lancet Neurol 2006;5:140-7

20. Lancet Neurol 2006;5:140-7

21. Lancet Neurol 2006;5:140-7 Time SAQLI symptoms domain maintained above 75% of prerandomization assessment Bulbar Non-Bulbar

22. Are NIV trials necessaries in ALS with non-bulbar impairement? Servera E. Sancho S. Lancet Neurol 2006;5:140-7 Ethical issues Non-bulbar patients in control group Stop studies according the results Technical issues Assessment effects of NIV Pressure vs volume ventilators Secretion management It’s mandatory to evaluate therapy “package”

23. Chest 2007;132:62-9 Median survival time 37 months Lenght of hospital stay 55 days (7-124) 91% home discharge

25. Zoccolella S et al. J Neurol 2007;254:1107-12 No improvements in survival: Low rate of interventions?

26. Survival of Irish ALS patients One year mortality was decreased by 29.7%

27. Survival of Irish ALS patients with bulbar onset Prognosis of bulbar onset patients was extended by 9.6 months

28. ALS patients who received their care at a multidisciplinary clinic had a better prognosis Recruitment bias ALS clinic treated a group of fitter ALS patients General neurologists saw all ALS patients Living further from ALS clinic More disabled Increased age Bulbar onset Shorter duration of illness Hutchinson M. J Neurol Neurosurg Psychiatry 2004;75:1208-12

29. J Neurol Neurosurg Psychiatry 2006;77:948-50 Tertiary center Neurology clinic 1080 days 775 days The median survival from onset was 10 months longer in ALS centers 4 yrs younger PEG & NIV more often Less hospital admissions

30. Chest 2007;127:2132-8 Early systematic respiratory evaluation is necessary to improve the results Of HMV in ALS Survival in patients without bulbar involvement Protocol Pre-Protocol

31. www.has-sante.fr/ 2003 17 Reference centers Coodination Working groups Local organization

32. Local organization Hôpital Pitié Salpetière Paris Multidisciplinary team Day hospital Respiratory unit Median survival on HMV: 18 months J. González-Bermejo, MD Visite de “ retourn d’annonce” Care planning Social support Call center 2-3 weeks after diagnostic

33. Reference centers: benefits and limits Improve skills & knowledge Distance Unnecessary referals + - Escarrabill J. Arch Bronconeumol 2007;43:527-9 Patient-centered care : accessibility vs performance

34. Conclusions Nihilism is bad It seems that patients don’t like agressive treatments Integrated care is a good option