Motor Neuron Diseases

Where is the lesion?

• Idiopathic acquired motor neuron diseases

• Spinal muscular atrophy

• Polio

• West Nile virus

• Paraneoplastic motor neuronopathy/neuropathy

• HIV associated motor neuronopathy/neuropathy

• Sometimes hard to distinguish from axonopathies

(MMN, Hexoseaminidase A deficiency)

Idiopathic Acquired Motor Neuron

Diseases

• Amyotrophic lateral sclerosis

• Progressive bulbar palsy

• Primary muscular atrophy

• Primary lateral sclerosis

Epidemiology

• Incidence: 0.4 to 2.4 per 100,000 population per

year in US

• 60% men

• Average age is mid 50s

Survival from Onset

• 50% at 3 to 4 years

• 20% at 5 years

• 10% at 10 years

• Rare patients live > 20 years without mechanical

ventilation

Pathology

• Selective degeneration of upper motor neurons

(cortical Betz cells), corticospinal and

corticobulbar tracts, and lower motor neurons

(anterior horn cells and motor cells in brainstem

nuclei).

• Contiguous spread in CNS

Diagnosis: El Escorial Criteria

Definite ALS—3 regions

Probable ALS—2 regions

Probable ALS, laboratory supported (EMG)

Possible ALS—1 region

Suspected ALS—just UMN or LMN findings

SOD-1

Possible Mechanisms—likely

multifactorial, ?polygenic predisposition

• Defective glutamate metabolism

• Autoimmune dysfunction/faulty microglia

• Viral infection (enterovirus, HTLV 1, HIV)

• Oxidative stress (SOD-1)

• Exogenous excitotoxins (Guamanian flying foxes)

• Mitochondrial damage

• Cytoskeletal abnormalities

• Apoptosis

Model for Mechanism in ALS

• Initiation—oxidative stress,

viral infection, exogenous

excitotoxins

• Propagation—glutamate

excitotoxicity, mitochondrial

dysfunction, cytoskeletal

abnormalities

• Contiguous spread—H2O2,

NOS

• Cell death—apoptosis

More than one disease?

• Inhibits glutamate release

• Inactivates voltage-dependent

sodium channels

• Prolongs survival by average of

three months

• Expensive

• Potential side effects require

monitoring

(Useless) Nerve Growth Factors

• BDNF

• CNTF

• GDNF

• IGF-1 (Myotrophin)

• SR57746A (Xaliprodin)

Speech/Communication—

Augmentative communication

devices

• Pencil and paper

• Voice amplifiers

• Communication boards

• Computerized communication devices

Swallowing

• Importance of maintaining weight

• Thickeners

• Supplements

• Early PEG placement if desired (FVC >50%)

Salivation

• Anticholinergic drugs

• Suction machines

• Botulinum toxin

• Salivary gland irradiation as last resort

Sleep/Fatigue

• Slow down, take rest breaks; wheel chairs for convenience

• Sleep disturbance, often the result of central apneas

• Other sleep disturbances due to muscle cramping,

myoclonus, restless legs—may respond to clonazepam,

Neurontin, levodopa, quinine

• Stimulants?

Signs of Pulmonary Dysfunction

• Dyspnea on exertion

• Orthopnea

• Morning headaches

• Excessive daytime sleepiness

• Monitor FVC, not ABG; supine FVC?

Treatment of Pulmonary Dysfunction

• Elevate head of bed

• Incentive spirometry and air stacking; guaifenisin; chest

wall oscillation therapy

• BiPAP—for nocturnal and PRN use—for both comfort and

increased survival

• Can have lengthy life-extension using mechanical ventilator,

but most patients choose not to use this due to quality of life

issues

• Discuss decision re: mechanical ventilator before it becomes

emergent—consider Living Will

Mobility

• AFOs for foot drop seen with early lower limb weakness

• Cervical collar for neck pain/head drop

• Four-prong canes

• Wheeled walker

• Wheel chairs—need to anticipate future needs

Activities of Daily Living

• Home evaluation per occupational therapist

• Grab bars, shower chair, raised toilet seat

• Large handled utensils for eating, grasping, writing

• Loose fitting clothes with Velcro, assistive devices for

zippers and buttons

• Assistance with laundry, cooking, shopping, etc.

Affect/Depression

• “Pseudobulbar” emotional incontinence

• Depressing disease

• Denial-Anger-Bargaining-Depression-Acceptance

• SSRIs, TCAs

Summary

• ALS is prototypical motor neuron disease

• Several potential causes for ALS have been identified

• Ultimately disease treatment will likely require multiple

agents with different mechanisms of action working at

different points in the cascade of events that cause ALS

• Quality of life can remain acceptable if attention is paid to

symptomatic treatment