Amyotrophic Lateral Sclerosis

Jaffar Khan, MD

Assistant Professor of Neurology

Emory University

Motor Neuron DiseaseTerminology

Lower motor neuron Upper motor neuron

 

 

ProgressiveMuscular Atrophy

Amyotrophic Lateral Sclerosis

Primary LateralSclerosis

Amyotrophic Lateral SclerosisPathology

Degeneration and death of motor nerves• Upper Motor Neuron

– within brain/spinal cord

• Lower Motor Neurons – leaves brain (stem)/spinal cord

Relatively spared• Eye movements and bowel/bladder function

Amyotrophic Lateral SclerosisEpidemiology

Etiology – unknown Average age of onset mid-50’s Mode of transmission

• Sporadic – 90-95%• Familial – 5-10% (autosomal

dominant)

Amyotrophic Lateral SclerosisEpidemiology

Male : Female – 3:2 U.S. Prevalence: 30,000 Incidence 1-2.5 / 100,000 Isolated areas of increased incidence

• Kii peninsula of Japan• Chamorro natives of Guam

Amyotrophic Lateral SclerosisClinical Presentation

Lower motor neuron signs• Weakness, muscle wasting, hyporeflexia,

muscle cramps, fasciculations

Upper motor neuron signs• Spasticity, hyperreflexia, weakness

Amyotrophic Lateral SclerosisClinical Presentation

Asymmetric Weakness – most common Onset single limb or bulbar Local spread then regional spread

• Bulbar, cervical, thoracic, lumbosacral Fasciculations

Amyotrophic Lateral SclerosisDiagnosis

Prominent upper and lower neuron signs with a progressive course without significant sensory or sphincter abnormalities

Laboratory investigation to search for a more treatable condition

Amyotrophic Lateral SclerosisClinical Signs and Symptoms

Weakness Hyporeflexia Pain and cramps Fasciculations Wasting

Spasticity Hyperreflexia Babinski’s sign Emotional Lability

Amyotrophic Lateral SclerosisAtypical Features

Dementia - < 5 % Sensory loss – atypical 25% complain of paresthesias Oculomotor dysfunction Bowel or bladder dysfunction

Amyotrophic Lateral Sclerosis

Diagnosis Two experienced Neurologists

Laboratory Studies

No study to prove or disproveLook for an alternate diagnosis

Amyotrophic Lateral SclerosisLaboratory Studies

Nerve conduction studies • assess for demyelinating vs. axonal

involvement Electromyography

• confirm ALS• myopathy

Amyotrophic Lateral SclerosisLaboratory Studies

MRI cervical spine • Cervical Spondylosis with cord compression• Herniated disc• Syrinx

Amyotrophic Lateral SclerosisLaboratory Studies

ESR – inflammatory/malignancy SPEP – monoclonal gammopathy TSH – hyperthyroidism B12 – combined systems degeneration

Calcium/PTH - hyperparathyroidism

Amyotrophic Lateral SclerosisPrognosis

Variable – difficult to predict in an individual patient

50% live 3-4 or more years 20% live 5 or more years 10% live 10 or more years Occasional patients live 20 years

Amyotrophic Lateral SclerosisTreatment

Rilutek 2 large clinical trials

• Bulbar onset• Entire population

Endpoint • Death• Ventilator dependence

Amyotrophic Lateral SclerosisTreatment

Bulbar onset • Prolonged survival • Improved muscle strength

Entire population• Prolonged survival• No effect on decline in muscle strength

Prolonged survival an average of 2-3 months

Amyotrophic Lateral SclerosisRilutek 50 mg po bid

Hepatotoxicity• Serum transaminase levels• Check every month x 3• Then every 3 months x 3 for the first year

Adverse effects• Neutropenia• Nausea/vomiting

Amyotrophic Lateral SclerosisRilutek 50 mg po bid

Reasons for not taking the drug• Expense• Minimal benefit• Unwillingness to take a medication that

would prolong life

Amyotrophic Lateral SclerosisManagement

weakness fatigue nutrition dysphagia feeding tube dysarthria communication

spasticity cramps pain depression anxiety breathing end-of -life

Amyotrophic Lateral SclerosisMultidisciplinary Approach to Care Neurologist Clinical/research nurse Dietician Speech/swallowing

therapist Family/caregivers Psychologists

Physical therapist Occupational therapist Social worker GI physician Support organizations Homehealth/hospice Pulmonologist