1. Amyotrophic Lateral Sclerosis

2. Motor Neuron Disease Terminology Lower motor neuron Upper motor neuron Progressive Muscular Atrophy Amyotrophic Lateral Sclerosis Primary Lateral Sclerosis

3. Amyotrophic Lateral Sclerosis Pathology u Degeneration and death of motor nerves Upper Motor Neuron –within brain/spinal cord Lower Motor Neurons –leaves brain (stem)/spinal cord u Relatively spared Eye movements and bowel/bladder function

4. Amyotrophic Lateral Sclerosis Epidemiology u Etiology – unknown u Average age of onset mid-50’s u Mode of transmission Sporadic – 90-95% Familial – 5-10% (autosomal dominant)

5. Amyotrophic Lateral Sclerosis Epidemiology u Male : Female – 3:2 u U.S. Prevalence: 30,000 u Incidence 1-2.5 / 100,000 u Isolated areas of increased incidence Kii peninsula of Japan Chamorro natives of Guam

6. Amyotrophic Lateral Sclerosis Clinical Presentation u Lower motor neuron signs Weakness, muscle wasting, hyporeflexia, muscle cramps, fasciculations u Upper motor neuron signs Spasticity, hyperreflexia, weakness

7. Amyotrophic Lateral Sclerosis Clinical Presentation u Asymmetric Weakness – most common u Onset single limb or bulbar u Local spread then regional spread Bulbar, cervical, thoracic, lumbosacral u Fasciculations

8. Amyotrophic Lateral Sclerosis Diagnosis u Prominent upper and lower neuron signs with a progressive course without significant sensory or sphincter abnormalities u Laboratory investigation to search for a more treatable condition

9. Amyotrophic Lateral Sclerosis Clinical Signs and Symptoms u Weakness u Hyporeflexia u Pain and cramps u Fasciculations u Wasting u Spasticity u Hyperreflexia u Babinski’s sign u Emotional Lability

10. Amyotrophic Lateral Sclerosis Atypical Features u Dementia - < 5 % u Sensory loss – atypical u 25% complain of paresthesias u Oculomotor dysfunction u Bowel or bladder dysfunction

11. Amyotrophic Lateral Sclerosis Diagnosis u Two experienced Neurologists Laboratory Studies No study to prove or disprove Look for an alternate diagnosis

12. Amyotrophic Lateral Sclerosis Laboratory Studies u Nerve conduction studies assess for demyelinating vs. axonal involvement u Electromyography confirm ALS myopathy

13. Amyotrophic Lateral Sclerosis Laboratory Studies u MRI cervical spine Cervical Spondylosis with cord compression Herniated disc Syrinx

14. Amyotrophic Lateral Sclerosis Laboratory Studies u ESR – inflammatory/malignancy u SPEP – monoclonal gammopathy u TSH – hyperthyroidism u B 12 – combined systems degeneration u Calcium/PTH - hyperparathyroidism

15. Amyotrophic Lateral Sclerosis Prognosis u Variable – difficult to predict in an individual patient u 50% live 3-4 or more years u 20% live 5 or more years u 10% live 10 or more years u Occasional patients live 20 years

16. Amyotrophic Lateral Sclerosis Treatment u Rilutek u 2 large clinical trials Bulbar onset Entire population u Endpoint Death Ventilator dependence

17. Amyotrophic Lateral Sclerosis Treatment u Bulbar onset Prolonged survival Improved muscle strength u Entire population Prolonged survival No effect on decline in muscle strength u Prolonged survival an average of 2-3 months

18. Amyotrophic Lateral Sclerosis Rilutek 50 mg po bid u Hepatotoxicity Serum transaminase levels Check every month x 3 Then every 3 months x 3 for the first year u Adverse effects Neutropenia Nausea/vomiting

19. Amyotrophic Lateral Sclerosis Rilutek 50 mg po bid u Reasons for not taking the drug Expense Minimal benefit Unwillingness to take a medication that would prolong life

20. Amyotrophic Lateral Sclerosis Management u weakness u fatigue u nutrition u dysphagia u feeding tube u dysarthria u communication u spasticity u cramps u pain u depression u anxiety u breathing u end-of -life

21. Amyotrophic Lateral Sclerosis Multidisciplinary Approach to Care u Neurologist u Chiropractor u Dietician u Speech/swallowing therapist u Family/caregivers u Psychologists u Physical therapist u Occupational therapist u Social worker u GI physician u Support organizations u Homehealth/hospice u Pulmonologist