ALS Overview

By SWA

Update: SOD1 gene screening in ALS – frequency of mutations, patients’
attitudes to genetic information and transition to tofersen treatment
in a multi-center program
 https://www.tandfonline.com/doi/epdf/10.1080/21678421.2024.2401131

In German language:

ALS Podcast #14: ALS & Huntington mit Dr. Patrick Weydt
https://www.youtube.com/watch?v=MyBf2AlS2aM&t=178s

Amyotrophic Lateral Sclerosis (ALS): A Detailed Exploration

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder that primarily affects motor neurons in the brain and spinal cord. This leads to muscle weakness, atrophy, and ultimately paralysis. Understanding the many triggers, risk factors, and biological influences on ALS is essential to improving treatment options and providing comprehensive care.

Viral Triggers of ALS

HIV and ALS

Research has shown that HIV can trigger ALS-like symptoms. In particular, a 2007 study published in Neurology reported that some HIV-positive individuals developed a condition resembling ALS that responded well to antiretroviral therapy.

Read the study:
HIV-related motor neuron disease mimicking ALS (Neurology, 2007)

How ALS is diagnosed:

    1. Clinical evaluation:

    A thorough neurological examination and assessment of symptoms, including muscle weakness, twitching, and speech difficulties, are crucial.

2. Ruling out other conditions:

Various tests are used to exclude other potential diagnoses, such as:

Electromyography (EMG) and nerve conduction studies: These assess the electrical activity of muscles and nerves to identify nerve damage or muscle dysfunction.

MRI scans: These create detailed images of the brain and spinal cord to identify any abnormalities or damage.

Blood and urine tests: These help rule out other conditions like infections, inflammation, or metabolic disorders.

Spinal tap (lumbar puncture): This procedure can help analyze cerebrospinal fluid to identify potential neurological issues.

For more information and resources on managing ALS, visit the following links:

 

Diaphragm Dysfunction in ALS

The diaphragm plays a critical role in breathing, and its impairment is a significant symptom of ALS.

Stiff (Tight) Diaphragm

Definition:
A diaphragm that remains contracted and tense, rather than relaxing during inhalation.

Causes:

  • Stress and emotional tension

  • Poor posture

  • Abdominal muscle tightness

  • Diaphragmatic spasms (e.g., after intense exercise)

Symptoms:

  • Tightness in the chest

  • Shortness of breath

  • Pain in the sides when coughing or sneezing

  • Neck and shoulder soreness

  • Digestive discomfort

"Collapsed" (Weak or Paralyzed) Diaphragm

Definition:
A diaphragm that loses its strength, often due to nerve damage or neuromuscular conditions like ALS.

Causes:

  • Neuromuscular disorders (ALS, MS, muscular dystrophy)

  • Phrenic nerve injury

  • Chronic lung diseases (e.g., COPD)

  • Spinal cord injury or diabetes-related neuropathy

Symptoms:

  • Shortness of breath, especially when lying flat

  • Difficulty breathing at rest

  • Poor sleep due to respiratory difficulty

  • Low blood oxygen levels (hypoxemia)

    Triggers and Risk Factors for ALS

Genetic Factors

Over 40 genes have been associated with ALS. The most commonly implicated include:

  • C9orf72

  • SOD1

  • TARDBP

  • FUS

These mutations help explain familial ALS and shed light on disease mechanisms.

Learn more:
NINDS: ALS Genetics Overview

Neuroinflammation in ALS

Inflammation plays a major role in ALS progression. Key features include:

  • Microglial activation

  • Reactive astrocytosis

  • Lymphocyte and macrophage infiltration

  • Complement system involvement

Source:
NIH: Neuroinflammation in ALS

Environmental Factors

Potential contributors to ALS development include:

  • Heavy metal exposure (e.g., lead, mercury)

  • Viral infections

  • Physical trauma

Psychological and Emotional Factors

Depression and ALS

Depression—especially in older adults—has been linked to a higher risk of ALS. It's unclear if depression is a prodromal symptom or a response to subclinical disease progression.

Pseudobulbar Affect (PBA)

PBA is common in ALS patients, marked by involuntary emotional outbursts (laughing or crying) that do not reflect the person's actual feelings.

More on PBA:
What Is PBA? (National Institute of Neurological Disorders and Stroke)

Hormonal Influences on ALS

Amylin and Insulin

Slower ALS progression has been observed in patients with elevated levels of amylin and insulin. Amylin is a metabolic hormone secreted alongside insulin and plays a role in appetite regulation and glucose metabolism.

Read more:
Amylin and ALS – Journal Reference (PubMed)

Stress and ALS

Contrary to popular belief, large-scale studies have not found strong evidence linking chronic stress or occupational stress to the development of ALS.

 Study example:
Psychosocial stress and ALS risk (Neurology, 2020)

Summary

ALS is a multifactorial disease shaped by:

  • Genetic mutations

  • Environmental exposures

  • Inflammatory responses

  • Possible hormonal and viral influences

While HIV has been shown to mimic ALS in rare cases (and is treatable), there is currently no clear evidence supporting a similar role for COVID-19.

References

  1. National Institute of Neurological Disorders and Stroke. (n.d.). Amyotrophic Lateral Sclerosis (ALS) Fact Sheet. Retrieved from https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/amyotrophic-lateral-sclerosis-als-fact-sheet
  2. Mayo Clinic. (n.d.). Amyotrophic Lateral Sclerosis (ALS). Retrieved from https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022

Further Reading and References

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

 

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