Amyotrophic Lateral Sclerosis(ALS)

Amyotrophic Lateral Sclerosis is the most common type of Motor Neuron Disease (MND). It is the same disease that  Stephen Hawking, a famous Nobel prize-winning physicist, was diagnosed with it. He was diagnosed with MND in 1975, and he was the longest survivor of MND. People who suffer from MND usually die due to respiratory failure and/or lung infection after getting bedridden. Stephen Hawking also died due to lung infections. ALS has no effects on Higher mental functions. Only Lower Motor Neurons and upper motor neurons are affected.

Understanding Amyotrophic Lateral Sclerosis (ALS)

• Amyotrophic
  • Denervation of Muscles due to damage to the anterior horn cells of the spinal cord
  • Lower motor neuron (LMN) lesion symptoms
    • Fasciculations
    • Areflexia
• Lateral Sclerosis
  • Involvement of Corticospinal pathway. There is thinning of the lateral columns.
  • Upper motor neuron (UMN) lesion symptoms
    • Brisk reflexes
    • Babinski sign

ALS is a Neurodegenerative disorder of adult-onset and there is no pediatric onset seen ever.

Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)

There are two pathogenic pathways of ALS

• Genetic causes 
  • SOD 1 Gene: This gene controls the activity of superoxide dismutase. Superoxide dismutase controls and neutralizes the free radicals in the body. Due to the SOD 1 gene defect, the activity of superoxide dismutase is decreases. This causes decreased Neutralization of free radicals. As a result, Free radicals are increased.
    • Anterior horn cells of spinal cord are damaged.
    • Pyramidal neurons in brain are damaged
    • the Corticospinal pathway is damaged

This causes thinning of the lateral columns. Thus causing ALS.

• G9orF72 gene: Hexanucleotide repeats
• Sporadic causes

Pathology in Amyotrophic Lateral Sclerosis (ALS)

There is a Defective protein degradation in neuron which causes a defective RNA processing. There is also Excitatory damage due to amino acids - Excitotoxicity

• Glutamate levels ↑
• Aspartate levels ↑

Clinical Manifestations of Amyotrophic Lateral Sclerosis (ALS)

• Initial (usually till 1 year)
  • Leg weakness
  • Fasciculations of thigh
  • Knee jerk was absent in one leg
  • Slapping gait
• After 1 year
  • Hand weakness
  • Brisk Bicep jerk
  • Asymmetrical nature (left leg and right hand, or right leg and left hand)
• Asymmetric gradual onset weakness.
• Eye movements are preserved
• Bladder and bowel movements are under control (hygiene is maintained)
• Higher mental functions are normal
• Later (after a few years)
  • Bulbar palsy
    • 9th and 10th cranial nerves - Can’t drink water
    • 12th cranial nerve - Can’t talk and eat
• If any 3 or >3 of the below 4 segments is involved, it is a confirmatory diagnosis of ALS
  • Bulbar
  • Cervical
  • Thoracic
  • Lumbosacral

Work Up of Amyotrophic Lateral Sclerosis (ALS)

Rule out hypokalemia

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If Normal

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Conduct NCV (Nerve Conduction Velocity)

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If Normal

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CPK MM and Muscle biopsy

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If Normal

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Anti Choline receptor antibody or Anti Musk antibody (rule out Myasthenia Gravis)

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If Normal

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Anti P/Q antibody test (rule out Lambert Eaton syndrome)

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If Normal

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Genetic studies like SCN4A channel study (rule out channelopathies like hypokalemic periodic paralysis or hyperkalemic periodic paralysis)

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If Normal

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Ruling out for ALS to be performed

Evaluation at Spinal Cord and Muscle

Excitatory damage due to amino acids and Free radical damage

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Damage to Anterior horn cells of spinal cord (LMN)

Damage to Pyramidal neurons in brain (UMN)

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Thinning of the lateral columns

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ALS

• Damage to Anterior horn cells of spinal cord: LMN lesions (Progressive muscular atrophy)
• Damage to Pyramidal neurons in brain: UMN lesions (Progressive lateral sclerosis)
• Combination: LMN + UMN lesions (Amyotrophic lateral sclerosis - ALS)
• ALS is more common

Electromyography

It is not an investigation of choice rather it gives just gives a hint on ALS. It reports about the Denervation pattern present in all LMN lesion, not only ALS.

Serum Vit B12

• If normal suspected for ALS
• If not, look for other possibilities

Amyotrophic Lateral Sclerosis (ALS) Treatment 

• Drugs
  • Riluzole (↓ both glutamate and aspartate levels)
  • Edavarone
• Foot drop splints - As foot drop is seen
• Physiotherapy 
• Finger extension splint - For contractions
• Tracheostomy - To support the respiratory functions
• Cough assistive devices - For Bulbar palsy effects

Bulbar Palsy 

In bulbar palsy, there is damage to 9^th, 10^th, 11^th, and 12^th cranial nerve and Damage to the Nucleus of nerve + Nerve. In Pseudobulbar palsy, Corticobulbar fibers are involved.

Other Diseases with LMNL + UMNL 

• Sub-Acute Combined Demyelination Spinal cord (SACD) - Due to Vit B12 deficiency
• Friedreich Ataxia - Due to frataxin gene defect
• MND/ ALS - Damage to Anterior horn cells (spinal cord) and Pyramidal neurons (brain)

Frequently Asked Questions

Q. Which is the most common cause of death in ALS patients?

Answer: Respiratory failure (Pneumonia)

Q: Which are the genes responsible for causing Amyotrophic Lateral Sclerosis (ALS)?

Answer: SOD 1 Gene and G9orF72 gene

Q: What is the age group that Amyotrophic Lateral Sclerosis (ALS)  affects?

Answer: Adult age group

Q: What disease did Stephen Hawking have?

Answer: Amyotrophic Lateral Sclerosis (ALS)

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