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Amyotrophic Lateral Sclerosis

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Description: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to loss of muscle control.
Type: Amyotrophic lateral sclerosis (ALS) is a type of neurodegenerative disease. The type of genetic transmission for ALS can be either sporadic or familial. Sporadic ALS, which accounts for about 90-95% of cases, typically has no clear genetic cause or family history. Familial ALS, making up about 5-10% of cases, is inherited in an autosomal dominant manner, although autosomal recessive and X-linked patterns have also been reported.
Signs And Symptoms: The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor and lower motor neurons. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.
Prognosis: The prognosis for amyotrophic lateral sclerosis (ALS) is generally poor. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to loss of muscle control. Over time, patients experience increasing muscle weakness and atrophy, leading to difficulties with speaking, swallowing, and breathing. The rate of progression can vary, but most people with ALS succumb to respiratory failure within 3 to 5 years from the onset of symptoms. However, some patients may live longer, particularly with interventions such as non-invasive ventilation and supportive care.
Onset: Amyotrophic lateral sclerosis (ALS) typically has an onset between the ages of 40 and 70, though it can occur at younger or older ages. Early symptoms often include muscle weakness, twitching, and cramping, usually starting in the hands, feet, or limbs, and gradually spreading to other parts of the body.
Prevalence: Amyotrophic lateral sclerosis (ALS) has a prevalence of about 2 to 5 people per 100,000 population in most parts of the world.
Epidemiology: ALS is the most common motor neuron disease in adults and the third most common neurodegenerative disease after Alzheimer's disease and Parkinson's disease. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women. The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old. The number of new cases is about 0.8 people per 100,000 per year in east Asia and about 0.7 people per 100,000 per year in south Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent. There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America. There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than the rest of the world, including Guam, the Kii Peninsula of Japan, and Western New Guinea. The incidence in these areas has decreased since the 1960s; the cause remains unknown.
People of all races and ethnic backgrounds may be affected by ALS, but it is more common in whites than in Africans, Asians, or Hispanics. In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West. Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks. There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is C9orf72, followed by SOD1, TARDBP, and FUS, while the most common ALS gene in Asia is SOD1, followed by FUS, C9orf72, and TARDBP.ALS can affect people at any age, but the peak incidence is between 50 and 75 years and decreases dramatically after 80 years. The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS; alternatively, ALS in the elderly might go undiagnosed because of comorbidities (other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS. In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group. Sporadic ALS usually starts around the ages of 58 to 63 years, while genetic ALS starts earlier, usually around 47 to 52 years. The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the world's population, especially in developing countries.
Intractability: Yes, amyotrophic lateral sclerosis (ALS) is considered intractable. It is a progressive neurodegenerative disease that currently has no cure, and treatment mainly focuses on managing symptoms and improving quality of life.
Disease Severity: The progression and severity of amyotrophic lateral sclerosis (ALS) can vary widely among individuals. It typically leads to muscle weakness, disability, and eventually death, usually within 3 to 5 years after symptom onset, although some people may live longer. The severity of the disease tends to increase over time, leading to significant impairment in motor function and independence.
Healthcare Professionals: Disease Ontology ID - DOID:332
Pathophysiology: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord. The pathophysiology of ALS involves the gradual degeneration and death of motor neurons, leading to muscle weakness, atrophy, and eventually, loss of voluntary muscle control. This process is influenced by a combination of genetic mutations, abnormal protein aggregation, mitochondrial dysfunction, oxidative stress, and impaired axonal transport. Additionally, neuroinflammation and excitotoxicity, primarily due to excessive glutamate activity, play crucial roles in disease progression. Despite ongoing research, the precise mechanisms of motor neuron degeneration in ALS remain incompletely understood.
Carrier Status: Amyotrophic lateral sclerosis (ALS) is typically not associated with carrier status as it is primarily a non-hereditary disease. However, around 5-10% of ALS cases are familial, involving inherited genetic mutations. For individuals with a family history of ALS, genetic testing can identify mutations in specific genes, such as SOD1, C9orf72, TARDBP, and FUS, which may indicate a risk of developing the disease. Carrier status is more relevant to recessive genetic conditions, whereas ALS is usually inherited in an autosomal dominant manner when it is familial.
Mechanism: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons, leading to progressive muscle weakness and atrophy.

**Mechanism:**
The disease mechanism involves the degeneration and death of upper and lower motor neurons in the brain and spinal cord. This neuronal loss disrupts the signaling between the brain and muscles, causing muscle weakness, atrophy, and eventually paralysis.

**Molecular Mechanisms:**
1. **Protein Aggregation:** Mutations in genes like SOD1, TDP-43, and FUS lead to the misfolding and aggregation of these proteins, which can be toxic to neurons.
2. **Oxidative Stress:** Excess reactive oxygen species (ROS) can damage cellular components, a process exacerbated by mutations in the SOD1 gene.
3. **Mitochondrial Dysfunction:** Impaired mitochondrial function leads to energy deficits and increased ROS production, contributing to neuronal cell death.
4. **Glutamate Excitotoxicity:** Impaired glutamate transport results in excessive extracellular glutamate, causing overactivation of glutamate receptors and neuronal damage.
5. **Axonal Transport Defects:** Mutations affect intracellular transport mechanisms, disrupting the movement of essential molecules and organelles along motor neuron axons.
6. **RNA Metabolism Defects:** Mutations in TDP-43 and FUS affect RNA processing, splicing, and stability, resulting in dysfunctional RNA metabolism.
7. **Neuroinflammation:** Activation of microglia and astrocytes leads to the release of pro-inflammatory cytokines, contributing to neuronal damage.

Research continues to elucidate the complex interplay of these molecular mechanisms in ALS pathogenesis.
Treatment: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder affecting motor neurons. Current treatment options primarily focus on slowing disease progression and managing symptoms.

Approved treatments:
1. **Riluzole**: This medication can modestly increase survival by reducing glutamate-induced neurotoxicity.
2. **Edaravone**: Administered via intravenous infusion, it may slow functional decline in some patients.

Symptom management:
1. **Physical therapy**: Helps maintain mobility and function.
2. **Occupational therapy**: Assists in adapting to daily activities.
3. **Speech therapy**: Offers strategies for communication as speech becomes affected.
4. **Nutritional support**: Through dietary modifications or feeding tubes to address swallowing difficulties.
5. **Respiratory support**: Non-invasive ventilation or other respiratory aids as breathing muscles weaken.

ALS treatment requires a multidisciplinary approach tailored to the individual patient's needs.
Compassionate Use Treatment: For amyotrophic lateral sclerosis (ALS):

1. **Compassionate Use Treatment**: This involves the use of investigational drugs or therapies outside of clinical trials for patients who have exhausted all other treatment options. Patients can access these treatments through programs set up by pharmaceutical companies with approval from regulatory authorities such as the FDA in the United States.

2. **Off-label or Experimental Treatments**:
- **Edaravone (Radicava)**: Initially approved for intravenous use in ALS, it is sometimes used off-label in an oral formulation.
- **Nuedexta**: Primarily used for pseudobulbar affect, a condition associated with ALS, it has shown some benefits in ALS patients.
- **Stem Cell Therapy**: Although still experimental, various stem cell treatments are in clinical trials aiming to slow disease progression.
- **Gene Therapy**: Particularly for those with genetic forms of ALS, experimental gene therapies are being investigated in clinical trials.
- **Riluzole**: The first FDA-approved drug for ALS, also sometimes explored in higher doses or different forms (like liquid).

Always consult with healthcare providers to understand the risks and benefits of these treatments.
Lifestyle Recommendations: For amyotrophic lateral sclerosis (ALS), lifestyle recommendations typically focus on maintaining quality of life and functionality for as long as possible. Key suggestions include:

1. **Physical Therapy and Exercise**: Regular, low-impact exercises like walking, swimming, and stretching can help maintain muscle strength and mobility. Physical therapy can also help prevent joint stiffness and improve circulation.

2. **Respiratory Care**: Breathing exercises and the use of devices like non-invasive ventilation (BiPAP) can help maintain respiratory function.

3. **Nutrition**: Maintain a well-balanced, high-calorie diet to combat muscle wasting and weight loss. Thickened liquids and soft foods can be easier to swallow as swallowing difficulties progress.

4. **Speech Therapy**: Speech therapists can provide strategies and communication aids for those experiencing speech difficulties.

5. **Assistive Devices**: Utilize braces, walkers, wheelchairs, and adaptive tools to aid with daily activities and maintain independence.

6. **Psychological Support**: Engaging with support groups, counseling, or therapy can help manage the emotional challenges associated with ALS.

7. **Advanced Care Planning**: Making decisions about feeding tubes, respiratory support, and other medical interventions in advance ensures that personal wishes are respected.

Understanding and following these recommendations can help individuals manage symptoms and maintain the best possible quality of life with ALS.
Medication: Currently, medications for amyotrophic lateral sclerosis (ALS) include:

1. **Riluzole**: This medication is believed to reduce damage to motor neurons by decreasing the release of glutamate. It can extend survival by a few months.
2. **Edaravone**: This antioxidant medication may help to slow the decline in daily functioning in some people with ALS.

While there is no cure for ALS, these medications can help to manage symptoms and potentially slow disease progression.
Repurposable Drugs: Research on amyotrophic lateral sclerosis (ALS) has explored several repurposable drugs that may offer therapeutic benefits:

1. **Riluzole:** Originally approved specifically for ALS, it is noted for slowing disease progression by reducing glutamate-induced neuronal damage.
2. **Edaravone:** Another drug approved for ALS that demonstrates antioxidant properties to help mitigate oxidative stress.
3. **Lithium:** Studied for its potential neuroprotective effects, though results have been mixed.
4. **Gabapentin:** Initially used for neuropathic pain and epilepsy, it has been considered for its potential to modify disease progression.
5. **Tamoxifen:** Known for breast cancer treatment, it has been investigated for its role in modulating cellular signaling pathways in ALS.

These drugs are being studied continually for their efficacy and safety in treating ALS, aiming to improve patient outcomes and slow disease progression.
Metabolites: In amyotrophic lateral sclerosis (ALS), metabolic changes have been observed, although the specific metabolites involved can vary. Commonly noted changes include alterations in amino acids, lipid metabolism, and energy-related metabolites. For instance, elevated levels of glutamate, reduced levels of certain antioxidants like glutathione, and alterations in acetyl-CoA and other components of the TCA cycle have been reported. However, "nan" in your query isn't clear; if you are referring to a specific concept related to metabolites and ALS, please provide more details for a precise explanation.
Nutraceuticals: There is limited evidence on the effectiveness of nutraceuticals for amyotrophic lateral sclerosis (ALS). While some studies suggest potential benefits from certain supplements like antioxidants (e.g., vitamin E), omega-3 fatty acids, and coenzyme Q10, their impact on disease progression is not well-established. Patients should consult healthcare providers before starting any nutraceutical regimen.
Peptides: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Peptides and nanoparticles (nanotechnologies) are being explored in the research for potential therapeutic strategies for ALS. Peptides can serve as drug delivery agents, targeting specific cellular pathways and potentially reducing disease progression. Nanoparticles can enhance drug delivery to specific sites, increase the stability of therapeutic agents, and improve the delivery of drugs across the blood-brain barrier. These approaches are under investigation to develop new treatments that may slow disease progression or alleviate symptoms in ALS patients.