What Are the Main Causes of Amyotrophic Lateral Sclerosis?

ALS Causes, Diagnosis & Treatments: A Complete Guide

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neurone disease that affects both upper and lower motor neurones. This causes muscle weakness, fasciculations, loss of motion, and finally trouble breathing.

There is no known cure, but a good mix of drugs, breathing support, rehabilitation, and lifestyle changes can help reduce the disease's progress, keep people independent, and make their lives better overall.

This guide talks about the various causes of ALS, how doctors can confirm a diagnosis, the early indicators to look for before symptoms get worse, and the available therapies. Read on for more detailed information.

Understanding the Main Causes of ALS

Doctors are unsure what triggers ALS, but they think it has something to do with genetics, the environment, and stress on cells that damages motor neurones over time.

• Genetic mutations: About 25-40% of ALS cases are inherited from parents to children. A repeat expansion in the C9orf72 gene is the most prevalent type of genetic alteration. SOD1, FUS, and TARDBP are some other mutations.
• Oxidative stress: Free radicals can damage neurones in ALS, which stops cells from creating energy and kills them.
• Glutamate toxicity: Too much glutamate, a type of neurotransmitter, can make neurones work too hard, which can cause calcium to build up and hurt nerves.
• Protein misfolding and clumping: Proteins like TDP-43 clump together inside nerve cells, which makes them not work right.
• Inflammation in the nervous system: When immune cells in the brain and spinal cord are too active and release compounds that harm healthy neurones, it causes inflammation in the nervous system.
• Environmental risks: Some studies have found that being around pesticides, heavy metals, military service, and even really hard work can raise the risk of getting ALS.

There is no one cause of ALS, but a combination of these problems commonly leads to the breakdown of motor neurones in ALS patients.

How Do You Diagnose ALS?

Doctors use symptoms, neurological exams, and specific testing to figure out if someone has ALS. Since there is no single test that confirms ALS, doctors look for important indications and rule out other similar diseases.

• Clinical history and physical exam: Muscle weakness, twitching (fasciculations), spasticity, and alterations in reflexes that show injury to both upper and lower motor neurones are all things that neurologists look for.
• EMG and nerve conduction studies: EMG looks for electrical activity in muscles and shows symptoms of denervation and reinnervation. Peripheral neuropathies can be ruled out with nerve testing.
• MRI scans: Brain and spine MRIs rule out other possible causes, such as tumours, multiple sclerosis, or spinal cord compression.
• Blood and lab tests: Blood tests can screen for infections, autoimmune illnesses, vitamin deficiencies, and problems with the thyroid.
• Muscle biopsy: A small sample of muscle is extracted under local anaesthesia and looked at for inflammation, damage to fibres, or problems with proteins. Helps rule out disorders such as muscular dystrophy or myositis.
• Nerve biopsy: A segment of a sensory nerve, usually from the ankle, is taken out and looked at while the patient is awake. When a nerve illness other than ALS is suspected, including vasculitis or peripheral neuropathy, this is used.

Getting a diagnosis early helps patients start therapy, get help with breathing, and make plans for their care as the disease gets worse.

What Are the First Warning Signs of ALS?

ALS usually begins slowly and gets worse over time. Being able to spot early warning symptoms can help doctors make a diagnosis faster and treat it better.

• Muscle twitching (fasciculations): Fasciculations are little, involuntary muscular twitches that happen in the arms, shoulders, legs, or tongue.
• Subtle weakness: Patients may drop things, have trouble with keys, or have trouble opening jars because they are weak. The grasp on the hand frequently gets weaker first.
• Speech changes: People with bulbar-onset ALS may slur their words or speak with a nasal tone.
• Difficulty swallowing (dysphagia): Dysphagia, or trouble swallowing, can make it hard to swallow food or drink.
• Foot drop or tripping: Patients may have problems walking or trip a lot because their ankles are weak.
• Muscle stiffness or cramping: These may be worse at night or when it's cold outside.

Since ALS symptoms can look like those of other nerve or muscle problems, it's crucial to consult a neurologist as soon as signs are noticed.

What Treatments Are Available for ALS?

There is no cure for ALS; however, there are numerous FDA-approved treatments and supportive techniques that help slow its progress and make life better:

• Riluzole: A glutamate release inhibitor that slightly increases lifespan by postponing the need for a ventilator.
• Edaravone (Radicava): An antioxidant that is delivered intravenously. Randomised trials have indicated that it slows the deterioration in function in those with early-stage ALS.
• AMX0035 (Relyvrio): A combination of sodium phenylbutyrate and taurursodiol that has been approved to treat stress in the mitochondria and endoplasmic reticulum.
• Qalsody (tofersen): An antisense oligonucleotide medication that was recently approved and is only available through speciality facilities for people with SOD1-mutation ALS.
• Supportive care: Nutritional counselling, speech and swallow therapy, and physical therapy, all of which help control symptoms and keep people independent. Multidisciplinary ALS centres work together to ensure these services work together for the best results.

Clinical trials are currently looking into experimental treatments such as stem cell therapy, new gene therapies, and new neuroprotective medicines. The patient's genetic profile, stage of disease, functional status, and care goals all affect the treatment choices. ALS is a devastating and progressive disease, but if you catch it early and have proper care, you can maintain your life.

Recognising early signs, confirming the diagnosis with the correct testing, and understanding the many causes of ALS make it possible to adapt treatment to each person, which helps them live better and longer.