ALS

• By Arjun Puri and Navdeep Saini

Intro

• Amyotrophic Lateral Sclerosis • Neurodegenerative disease• Incurable and fatal• Can affect anyone• Life expectancy = 2-5 years

Etiology

• Sporadic – unknown• Familial – chromosome 21, autosomal dominant

• Mutations: SOD1, TARDBP and FUS, C9orf7

• Environmental risk factors• Smoking, military services, sport

• Western Pacific: Cycad nut• Glutamate

Epidemiology

• 2 deaths per 100,000 annually• West Pacific:

• Guam (143 cases per 100,000• Kii peninsula of Japan• New guinea

• Incidence rate: 2 per 100,000 people• Prevalence rate: 6-8 per 100,000 people• 2000 census = 22,600 Americans (prevalence)• Finland = highest rate

Clinical Research

20% physician-assisted suicide (Netherlands)

Spiritual care and bereavement comforts ppts.

Clinical Research (Cont.)Palliative care

• STUDY: 171 ppts: 90% died peacefully (no mechanical vent. Slipped from sleep to coma due to hypercapnia)

• Dyspnea treated with Morphine (2·5–5·0 mg orally or 1–2 mg subcutaneously or intravenously every 4 h)

• Oxygen admin. if signs of hypoxia

• lorazepam sublingually (beginning with 1·0–2·5 mg) or midazolam orally or subcutaneously (starting at 1–2 mg)

Treat the symptoms, not just the disorder!!!

Diagnostic Markers• Spirometry – progression of ALS in clinical trials (contraInd.

Prominent bulbar involvement)

• Maximum voluntary isometric contraction better to achieve objective measure of muscle strength (contraInd. Only fit individuals and depends on observer training)

• neurophysiological index is easily calculated from standard data obtained when calculating motor conduction velocity

Clinical Trials

• Adenoassociated virus exp. IGF-1 into G39A SOD1 transgenic mice – injected into resp. and limb muscles.

• Prolonged survival even when clinical features of ALS have appeared.

• Lentiviral inj admin. Once exp. EDGF delayed onset & slowed down progression, even when paralysis was present.

Stem Cell Therapy

• replacement of lost cells,• cell fusion, • neurotrophic factor release,• endogenous stem-cell proliferation, • Transdifferentiation

All under research, however ethical dilemma

Conclusion

• Increasingly important to develop new treatment strategies

• Drug delivery via intrathecal admin or viral vector (additional silencing mutant gene)

• Will remain progressive for multiple years – decades, importance of palliative care (QoC)

References

• http://www.alsa.org/about-als/• http://emedicine.medscape.com/

article/1170097

• Mitchell J.D., Borasio G.D,: Amyotrophic lateral sclerosis: Lancet; 369: 2031–41: 2007

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