Amyotrophic Lateral Sclerosis

Question 1

Which motor nuclei are relatively spared in ALS?

Answer 1

• Oculomotor nuclei of the eye
• Anal sphincter
• Bladder sphincter

Question 2

Coexistence of upper and lower motor neuron signs in spinal compression

Answer 2

Sometimes in spinal compression, the lower motor neurons at the level of compression as well as the upper motor neurons running inferiorly are simultaneously compressed

This results in mixed LMN and UMN signs. Specifically, one batch of LMN symptoms at one spinal level, and all UMN signs below this level.

Question 3

Amyotrophic lateral sclerosis

Answer 3

• Onset over the course of months in any age group over age 20 (young adults, middle aged, and older adults alike)
• 90% sporadic, 10% familial (with multiple modes of inheritance)
• Speech/swallow dysfunction is usually the presenting symptom, often accompanied by decreased manual dexterity
• Gradual UMN/LMN pattern paralysis with sparing of the brain and senses, eventually culminating in respiratory paralysis
• Diagnostic workup includes EMG-NCS and MRI. LP may also be indicated to evaluate for BBB disruption, inflammation, or malignant cells.
• Treatment: Riluzole or Radicava, supportive care

Question 4

Most common genes implicated in heritable ALS

Answer 4

• C9ORF72 (a copper-zinc transporter, also linked to frontotemporal dementia)
• SOD1 (superoxide dismutase 1)
  
  • Both are autosomal dominant

Question 5

C9ORF72 mutations

Answer 5

May present as ALS, FTD, or ALS and FTD

Question 6

The presence of coexisting UMN and LMN signs in a single limb

Answer 6

Highly suggestive of ALS

Question 7

Things that may mimic ALS

Answer 7

• Spinal:
  
  • Spinal cord tumor
  • Herniated disc
  • Syringomyelia
  • Cervical spine degeneration (spondylosis, spondylolisthesis)
• Infectious:
  
  • HIV
  • HTLV
  • Syphilis
  • Lyme
  • Post-polio syndrome
• Toxic-metabolic:
  
  • B12 deficiency (subacute combined degeneration)

Question 8

El Escorial diagnostic criteria for ALS

Answer 8

• Presence of both upper and lower motor neuron signs in at least three separate regions, including:
  
  • Upper extremities
  • Lower extreities
  • Tongue/speech
  • Paraspinal muscles
• Utilizing clinical, laboratory, radiographic, and pathological results

Question 9

Riluzole

Answer 9

• Reduces damage to motor neurons by acting at voltage-gated sodium channels and decreasing the release of glutamate
  
  • Acts via the “excitotoxicity” theory of ALS
• Extends the time for ALS patients to requirement for ventilatory support
• While taking, patients must be monitored for liver damage

Question 10

Neudexta

Answer 10

Reduces pseudobulbar affect in ALS

Question 11

Categories to exclude when suspecting ALS

Answer 11

• Structural
  
  • Brain/spine MRI
  • EMG-NCS
• Metabolic
  
  • Vitamins
  • BMP
  • Extended lytes
• Infection
  
  • Titers for HIV, HTLV, syphilis, Lyme
  • CSF investigations

Question 12

Radicava

Answer 12

Second FDA-approved drug for ALS

Delays disability in ALS patients treated at an early stage of disease

Question 13

Tongue fasciculations

Answer 13

Have multiple causes, but ALS is a classic association