As a lot of you have shown interest in ALS, I thought this would be a good time to dwell into its pathophysiology. I shall try to explain what happens in ALS in simple terms. ALS as has been pointed out is a motor neuron disease. What does one mean by motor neuron disease (MND)?
In the human body we have motor neurons and sensory neurons. Motor neurons refer to nerve cells and their bodies which control motor movements for example a motor neuron helps you to move your fingers or move your toes. We have sensory neurons too, these help us to perceive sensations like temperature (when you touch a hot cup of coffee), pain (you step on a nail—ouuuchhh) and touch (you touch a soft coat made of fur).
Each neuron whether motor or sensory has a cell body and then has a process called the axon (think of it as a body and its tail). The motor neurons which control the movements of the arms and legs are located in the spinal cord (we refer to them as the anterior horn cells becuase they lie anterioly in the spinal cord). We also have motor neurons which control other movements like that of swallowing, speech etc. These neurons lie in the brain stem (the lower part of the brain). MND’s like ALS cause the death of these motor neurons in the spinal cord (anterior horn cells) and those in the brain stem. In its classical form, ALS does not affect the sensory neurons hence it is called a motor neuron disease. Once the motor neurons in the anterior horn cells and the brainstem die they do not regenerate again and hence ALS is also a neurodegenerative disease causing progressive relentless degeneration of motor neurons.
So the next question arises what causes the death of these motor neurons? Why suddenly in a healthy person the motor neurons start dying? Why is this death irreversible? Why are only the motor neurons affected why not the sensory neurons? Why are other parts of the brain not affected?
No one quite knows the answers to any of the above question. Why is the death so selective that it only affects the motor neurons and spares everything else. As the disease progresses and more and more motor neurons die, the patient is left paralysed (wheelchair or bed bound) not able to eat or swallow with difficulty in speaking. The higher mental functions remain intact so the memory is as sharp as ever and that is what becomes so difficult both for the patient and the caregivers (you can only imagine what it must feel like been trapped in a body which is paralysed). There is a form of ALS which runs in some families, this has been referred to as familial ALS and is genetic in etiology. Mutations in the copper/ zinc superoxide dismutase (SOD) have been implicated in causing ALS. The role of oxidative stress and free radicals has also been mentioned in its pathophysiology but the disease does not respond even if you treat it with anti-oxidants.
Tremendous research is going on around the world in ALS and there are some very prominent labs here in U.S.A. working on it too. I would advise all patients and their caregivers to get in touch with an ALS specialist as he or she shall be the best informed if any new therapeutic modalities (medicines etc) become available.The ALS association is also a good organization to be in touch with. They can be reached at www.alsa.org.
Even though there is no cure there are a multitude of devices out there that can ease the life for a patient with ALS. My message hence is one of hope and I keep reading and am inspired by patient’s stories of living and winning the battle against ALS.
Email me at: firstname.lastname@example.org
2 thoughts on “ALS pathophysiology”
if you dont mind, i might add more things to share with your readers:
the main cause of ALS deaths is degeneration of respiratory muscles causing breathing difficulties
SOD1 gene is the primary gene linked to ALS, but there are also genes such as ANG, VEGF, TARDBP, CHMP2B now linked to it
and Riluzole is approved by the FDA for ALS treatment, but its effectiveness varies between individuals
Thank you for writing in. I try to write the blog in simple lay mans language and avoid getting too “medical” if I can help it.The information you contributed is most welcome.
Nitin Sethi, MD