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ALS:

Tolerance and survival predictors

ALS:

Tolerance and survival predictors

Cáceres, 10 de Noviembre de 2007

Dr. Joan Escarrabill Hospital Universitari de Bellvitge

L’Hospitalet (Barcelona)jescarra@csub.scs.es

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Agenda

Predictors of tolerance

NIV and survival

Survival and care organization

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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

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Predictors

PEG

Care organization

Bulbar involvement at onset

NIV

Secretions magement

Nihilism

Autonomy

Management of acute problems

Age at onset

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Limitations of the studies

Long-term studies:– Different diagnostic criteria– Incomplete data

Retrospective studies

Data from patients that “knock to the door”: not population-based studies

The role of PEG and NIV are, in general, underconsidered

No biomarkers

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Amyotrophic lateral sclerosis

Onset of symptoms

Firstvisit

Onset NIV

Medicaldelay

Unclearfirst symptom

PrecociousNIV

PalliativeEnd-of-life

NIV

Studies are difficult to compare

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Amyotrophic lateral sclerosis

Onset of symptoms

Firstvisit

Onset NIV

Medicaldelay

Unclearfirst symptom

PalliativeEnd-of-life

NIV

PrecociousNIV

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Amyotrophic lateral sclerosis

Onset of symptoms

Firstvisit

Onset NIV

Medicaldelay

Unclearfirst symptom

PrecociousNIV

PalliativeEnd-of-life

NIV

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J Neurol 2006;253:1428-36

Better survival

Younger age

Limb onset

Longer delay before first examination

Higher initial FVC = Longer survival

Lower initial AALS score

Includes assessment of swallowing, speech, and respiratory function, and both strength and function of upper and lower extremity musculature

Appel V. Ann Neurol. 1987;22:328-33.

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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 Swallowing4

3

21

0

4

3

21

0

Cedarbaum JM. J Neurol Sci 1999;169:13-21

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J Neurol Neurosurg Psychiatry 2004;75:1753-55

Scottish ALS Register

n=1226

Medical nihilism ?

Riluzole & PEG use increases

Patient autonomy

Less aggressive therapy

2.4 months

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ALS: Acute chest infection

Servera E. J Neurol Sci 2003;209:111-3

65 yrs old man

Daytime Mouth pieceNasal mask for nocturnal use

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Secretions management

MI-E

Ventilador+30 +TAT

Ventilador+TAT

Air stacking+TAT

TATSPON + m

ot

SPON

1100

1000

900

800

700

600

500

400

300

200

100

0

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٭

٭

٭

٭

†

††

†

‡

‡‡

• P

CF

l/m

n

Courtesy of Cristina Senent MD (H. Sant Joan - Alacant)& Jesus González MD (Hôpital Pitié-Salpetière - Paris)

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Bulbar impairment

BulbarNon-Bulbar

Bourke SC. Lancet Neurol 2006;5:140-7

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Survival in ALS patients with bulbar involvement

Farrero et al. Chest 2007;127:2132-8

NIV Tolerance

NIV intolerance

NIV Tolerance

NIV intolerance

Hypercapnia

Normocapnia

NIV Tolerance

NIV intolerance

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Agenda

Predictors of tolerance

NIV and survival

Survival and care organization

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Survival on HMVLaub M & Midgren B. Respir Med 2007;101:1074-8

n=1526

ALS

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Indication of NIV

Melo J. J Neurol Sci 1999;169:114-7

n=2357 patients

15% on NIV

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Lancet Neurol 2006;5:140-7

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Lancet Neurol 2006;5:140-7

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Lancet Neurol 2006;5:140-7

Time SAQLI symptoms domain maintained above 75% of prerandomization assessment

BulbarNon-Bulbar

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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”

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Chest 2007;132:62-9

Median survival time 37 months

Lenght of hospital stay55 days (7-124)

91% home discharge

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Agenda

Predictors of tolerance

NIV and survival

Survival and care organization

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Zoccolella S et al. J Neurol 2007;254:1107-12

No improvements in survival: Low rate of interventions?

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Survival of Irish ALS patients

One year mortality wasdecreased by 29.7%

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Survival of Irish ALS patients with bulbar onset

Prognosis of bulbar onset patients was extended by 9.6 months

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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 neurologistssaw all ALS patients

Living further from ALS clinicMore disabledIncreased ageBulbar onsetShorter duration of illness

Hutchinson M. J Neurol Neurosurg Psychiatry 2004;75:1208-12

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J Neurol Neurosurg Psychiatry 2006;77:948-50

Tertiary center

Neurology clinic

1080 days

775 days

The median survival from onsetwas 10 months longer

in ALS centers

4 yrs youngerPEG & NIV more oftenLess hospital admissions

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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

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www.has-sante.fr/

2003 17 Reference centers

CoodinationWorking groupsLocal organization

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Local organization

Visite de “retourn d’annonce”

Care planningSocial supportCall center

2-3 weeks after diagnostic

Hôpital Pitié SalpetièreParis

Multidisciplinary teamDay hospitalRespiratory unit

Median survival on HMV: 18 months

J. González-Bermejo, MD

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Escarrabill J. Arch Bronconeumol 2007;43:527-9

Patient-centered care: accessibility vs performance

Reference centers: benefits and limits

Improve skills & knowledge

DistanceUnnecessary referals

+

-

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Conclusions

Nihilism is bad

It seems that patients don’t like agressive treatments

Integrated care is a good option