Asteroids, including those in the asteroid belt have been suggested as a possible site of human colonization.
Some of the driving forces behind this effort to colonize asteroids
include the survival of humanity, as well as economic incentives
associated with asteroid mining.
The process of colonizing asteroids does have many obstacles that must
be overcome for human habitation, including transportation distance,
lack of gravity, temperature, radiation, and psychological issues.
Most asteroids have minerals that could be mined. Because these bodies do not have substantial gravity wells, only a low delta-V is needed to haul materials to a construction site.
There is estimated to be enough material in the main asteroid
belt alone to build enough space habitats to equal the habitable surface
area of 3,000 Earths.
Ceres
Ceres is a dwarf planet and the largest body in the asteroid belt. As it is cryovolcanic it has potential for asteroid mining
of resources for colonization. Its gravitational pull is stronger than
other bodies in the asteroid belt, making surface colonization a more
realistic possibility.
One of the primary arguments for space colonization is to ensure the long-term survival of the human species. In the event of worldwide artificial or natural disaster a space colony would allow the human species to continue on. Michael Griffin, the NASA administrator in 2006, stated the case as follows:
“...
the goal isn't just scientific exploration ... it's also about
extending the range of human habitat out from Earth into the solar
system as we go forward in time ... In the long run a single-planet
species will not survive ... If we humans want to survive for hundreds
of thousands or millions of years, we must ultimately populate other
planets.”
A specific argument for asteroid colonization is the potential economic gain from asteroid mining. Asteroids contain a significant amount of valuable materials, including rare minerals and precious metals,
which can be mined and transported back to Earth to be sold. With
approximately as much iron as the world produces in 100,000 years, 16 Psyche is one such asteroid worth approximately $10 quintillion in metallic iron and nickel. NASA is planning a mission for October 10, 2023 for the Psyche orbiter to launch and get to the asteroid by August 2029 to study. 511 Davida could have $27 quadrillion worth of minerals and resources.
NASA estimates that between 1.1 and 1.9 million asteroids in the
asteroid belt are larger than 1 kilometer in diameter. Millions are
smaller. Approximately 8% of known main belt asteroids are similar in
composition to 16 Psyche.
One company, Planetary Resources, is already aiming to develop
technologies with the goal of using them to mine asteroids. Planetary
Resources estimates some 30-meter long asteroids to contain as much as
$25 to $50 billion worth of platinum.
Interplanetary spaceflight is a challenge because the asteroid belt is far, hundreds of millions of miles or km away. A human mission to Mars, tens of millions of miles or km, is similarly challenging. The Mars rover mission, for example, took 253 days to get to Mars. Russia, China, and the European Space Agency ran an experiment, called MARS-500, between 2007 and 2011 to gauge the physical and psychological limitations of crewed space flight. The experiment concluded that 18 months of solitude was the limit for a crewed space mission.
With current technology the journey to the asteroid belt would be
greater than 18 months, suggesting that a crewed mission may be beyond
our current technological capabilities.
Asteroids are not large enough to produce significant gravity, making it difficult to land a spacecraft.
Humans have yet to land a spacecraft on an asteroid in the asteroid
belt, but uncrewed spacecraft have temporarily landed on a few
asteroids, the first of which in 2001 was 433 Eros, a NEA from the Amor group, more recently 162173 Ryugu, another NEA of the Apollo group. This was part of the Hayabusa2 mission that was conducted by the Japanese Space Agency. The landing used four solar ionic thrusters and four reaction wheels for orientation control and orbit control of the spacecraft to land on Ryugu. These technologies may be applied to complete a successful similar landing in the asteroid belt.
Since Mars is much closer to the Asteroid belt than Earth is, it would take less Delta-v to get to the Asteroid belt and return minerals to Mars. One hypothesis is that the origin of the Moons of Mars (Phobos and Deimos) are actually Asteroid captures from the Asteroid belt. Using the moon Phobos to launch spacecraft is energetically favorable and a useful location from which to dispatch missions to main belt asteroids. Mining the asteroid belt from Mars and its moons could help in the Colonization of Mars.
Lack of gravity has many adverse effects on human biology. Transitioning gravity fields has the potential to impact spatial orientation, coordination, balance, locomotion, and induce motion sickness. Asteroids, without artificial gravity, have relatively little gravity in comparison to earth. Without gravity working on the human body, bones lose minerals, and bone density decreases by 1% monthly. In comparison, the rate of bone loss for the elderly is between 1-1.5% yearly. The excretion of calcium from bones in space also places those in low gravity at a higher risk of kidney stones.
Additionally, a lack of gravity causes fluids in the body to shift
towards the head, possibly causing pressure in the head and vision
problems.
Overall physical fitness tends to decrease as well, and proper
nutrition becomes much more important. Without gravity, muscles are
engaged less and overall movement is easier. Without intentional training, muscle mass, cardiovascular conditioning and endurance will decrease.
Artificial gravity
Artificial gravity
offers a solution to the adverse effects of zero gravity on the human
body. One proposition to implement artificial gravity on asteroids,
investigated in a study conducted by researchers at the University of
Vienna, involves hollowing out and rotating a celestial body. Colonists would then live within the asteroid, and the centrifugal force
would simulate Earth's gravity. The researchers found that while it may
be unclear as to whether asteroids would be strong enough maintain the
necessary spin rate, they could not rule out such a project if the
dimensions and composition of the asteroid were within acceptable
levels.
Currently, there are no practical large-scale applications of
artificial gravity for spaceflight or colonization efforts due to issues
with size and cost. However, a variety of research labs and organizations have performed a number of tests utilizing human centrifuges
to study the effects of prolonged sustained or intermittent artificial
gravity on the body in an attempt to determine feasibility for future
missions such as long-term spaceflight and space colonization.
A research team at the University of Colorado Boulder found that they
were able to make all participants in their study feel comfortable at
approximately 17 revolutions per minute in a human centrifuge, without
the motion sickness that tends to plague most trials of small-scale
applications of artificial gravity.
This offers an alternative method which may be more feasible
considering the significantly reduced cost in comparison to larger
structures.
Temperature
Most asteroids are located in the asteroid belt, between Mars and Jupiter. This is a cold region, with temperatures ranging from -73 degrees Celsius to -103 degrees. Human life will require a consistent energy source for warmth.
One possibility for defense against this radiation is living
inside of an asteroid. It is estimated that humans would be sufficiently
protected from radiation by burrowing 100 meters deep inside of an
asteroid.
However, the composition of asteroids creates an issue for this
solution. Many asteroids are loosely organized rubble piles with very
little structural integrity.
Psychology
Space
travel has a huge impact on human psychology, including changes to
brain structure, neural interconnectivity, and behavior.
Cosmic radiation has the ability to impact the brain, and has been studied extensively on rats and mice. These studies show the animals suffer from decreases in spatial memory, neural interconnectivity, and memory. Additionally, the animals had an increase in anxiety and fear.
The isolation of space and difficulty sleeping in the environment
also contribute to psychological impacts. The difficulty of speaking
with those on earth can contribute to loneliness, anxiety, and depression.
A Russian study simulated the psychological impacts of extended space
travel. Six healthy males from various countries but with similar
educational backgrounds to astronauts lived inside an enclosed module
for 520 days in 2010–11. The members of the survey reported symptoms of moderate depression, abnormal sleep cycles, insomnia, and physical exhaustion.
In addition, NASA reports that missions on the global scale have ended or been halted due to mental issues. Some of these issues include shared mental delusions, depression, and becoming distressed from failed experiments.
However, in many astronauts, space travel can actually have a
positive mental impact. Many astronauts report an increase of
appreciation for the planet, purpose, and spirituality. This mainly results from the view of Earth from space.
Clinical
diagnosis of exclusion based on progressive symptoms of upper and lower
motor neuron degeneration in which no other explanation can be found.
Supportive evidence from electromyography, genetic testing, and neuroimaging
Life expectancy highly variable but typically 2–4 years after diagnosis
Frequency
Incidence: 1.6/100,000 individuals per year
Prevalence: 4.4/100,000 living individuals
Lifetime risk: 1 in 400 individuals
Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a rare and terminal neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common form of the motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, gradual increasing weakness, and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty in speaking or swallowing. Around half of people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Motor neuron loss continues until the abilities to eat, speak, move, or, lastly, breathe are lost.
Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause, often linked to a history of the disease in the family, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.
There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. Treatments that slow ALS include riluzole (extends life by two to three months) and sodium phenylbutyrate/ursodoxicoltaurine (extends life by around seven months). Non-invasive ventilation may result in both improved quality, and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60.
The average survival from onset to death is two to four years, though
this can vary, and about 10% of those affected survive longer than ten
years.
Descriptions of the disease date back to at least 1824 by Charles Bell.
In 1869, the connection between the symptoms and the underlying
neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.
As a disease, ALS itself can be classified in a few different
ways: by which part of the motor neurons are affected; by the parts of
the body first affected; whether it is genetic; and the age at which it
started. Each individual diagnosed with the condition will sit at a
unique place at the intersection of these complex and overlapping
subtypes, which presents a challenge to diagnosis, understanding, and
prognosis.
Subtypes of motor neuron disease
Classic ALS involves neurons in the brain and spinal cord (upper motor neurons, highlighted red), as well as the lower motor neurons, which go from the spinal cord to the muscles, highlighted teal.
ALS can be classified by the types of motor neurons that are affected. To successfully control any voluntary muscle in the body, a signal must be sent from the motor cortex in the brain down the upper motor neuron as it travels down the spinal cord. There, it connects via a synapse to the lower motor neuron
which connects to the muscle itself. Damage to either the upper or
lower motor neuron, as it makes its way from the brain to muscle, causes
different types of symptoms. Damage to the upper motor neuron typically causes spasticity including stiffness and increased tendon reflexes, and/or clonus, while damage to the lower motor neuron typically causes weakness, muscle atrophy, and fasciculations.
Classical, or classic ALS, involves degeneration to both the upper motor neurons in the brain and the lower motor neurons in the spinal cord. Primary lateral sclerosis (PLS) involves degeneration of only the upper motor neurons, and progressive muscular atrophy
(PMA) involves only the lower motor neurons. There is debate over
whether PLS and PMA are separate diseases or simply variants of ALS.
Classical ALS accounts for about 70% of all cases of ALS and can be
subdivided into where symptoms first appear as these are usually
focussed to one region of the body at initial presentation before later
spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of classical ALS affecting around 3% of patients is respiratory-onset, in which the initial symptoms are difficulty breathing (dyspnea) upon exertion, at rest, or while lying flat (orthopnea).
Primary lateral sclerosis
(PLS) is a subtype of the overall ALS category which accounts for about
5% of all cases and only affects the upper motor neurons in the arms,
legs, and bulbar region.
However, more than 75% of people with apparent PLS go on to later
develop lower motor neuron signs within four years of symptom onset,
meaning that a definitive diagnosis of PLS cannot be made until several
years have passed.
PLS has a better prognosis than classical ALS, as it progresses slower,
results in less functional decline, does not affect the ability to
breathe, and causes less severe weight loss than classical ALS.
Progressive muscular atrophy
(PMA) is another subtype that accounts for about 5% of the overall ALS
category and affects lower motor neurons in the arms, legs, and bulbar
region.
While PMA is associated with longer survival on average than classical
ALS, it is still progressive over time, eventually leading to
respiratory failure and death.
As with PLS developing into classical ALS, PMA can also develop into
classical ALS over time if the lower motor neuron involvement progresses
to include upper motor neurons, in which case the diagnosis might be
changed to classic ALS.
Rare isolated variants of ALS
Isolated
variants of ALS have symptoms that are limited to a single region for
at least a year; they progress more slowly than classical ALS and are
associated with longer survival.
These regional variants of ALS can only be considered as a diagnosis
should the initial symptoms fail to spread to other spinal cord regions
for an extended period of time (at least 12 months).
Flail arm syndrome is characterized by lower motor neuron damage
affecting the arm muscles, typically starting with the upper arms
symmetrically and progressing downwards to the hands.
Flail leg syndrome is characterized by lower motor neuron damage
leading to asymmetrical weakness and wasting in the legs starting around
the feet.
Isolated bulbar palsy is characterized by upper or lower motor neuron
damage in the bulbar region (in the absence of limb symptoms for at
least 20 months), leading to gradual onset of difficulty with speech (dysarthria) and swallowing (dysphagia).
Illustration
showing the range of upper and lower motor neuron involvement in the
two most common types of ALS (top row) and three of the most common rare
subtypes of ALS (bottom row)
Age of onset
ALS
can also be classified based on the age of onset. While the peak age of
onset is 58 to 63 for sporadic ALS and 47 to 52 for genetic ALS,
about 10% of all cases of ALS begin before age 45 ("young-onset" ALS),
and about 1% of all cases begin before age 25 ("juvenile" ALS).
People who develop young-onset ALS are more likely to be male, less
likely to have bulbar onset of symptoms, and more likely to have a
slower progression of the disease.
Juvenile ALS is more likely to be genetic in origin than adult-onset
ALS; the most common genes associated with juvenile ALS are FUS, ALS2, and SETX. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.
The start of ALS may be so subtle that the symptoms are overlooked.
The earliest symptoms of ALS are muscle weakness or muscle atrophy,
typically on one side of the body. Other presenting symptoms include
trouble swallowing or breathing, cramping, or stiffness of affected
muscles; muscle weakness affecting an arm or a leg; or slurred and nasal
speech. The parts of the body affected by early symptoms of ALS depend
on which motor neurons in the body are damaged first.
In limb-onset ALS, the first symptoms are in the arms or the
legs. If the legs are affected first, people may experience awkwardness,
tripping, or stumbling when walking or running; this is often marked by
walking with a "dropped foot"
that drags gently on the ground. If the arms are affected first, they
may experience difficulty with tasks requiring manual dexterity, such as
buttoning a shirt, writing, or turning a key in a lock.
In bulbar-onset ALS, the first symptoms are difficulty speaking
or swallowing. Speech may become slurred, nasal in character, or
quieter. There may be difficulty with swallowing and loss of tongue
mobility. A smaller proportion of people experience "respiratory-onset"
ALS, where the intercostal muscles that support breathing are affected first.
Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex.
While the disease does not cause pain directly, pain is a symptom
experienced by most people with ALS caused by reduced mobility.
Symptoms of lower motor neuron degeneration include muscle weakness and
atrophy, muscle cramps, and fleeting twitches of muscles that can be
seen under the skin (fasciculations).
Progression
Although
the initial site of symptoms and subsequent rate of disability
progression vary from person to person, the initially affected body
region is usually the most affected over time, and symptoms usually
spread to a neighbouring body region. For example, symptoms starting in
one arm usually spread next to either the opposite arm or to the leg on
the same side.
Bulbar-onset patients most typically get their next symptoms in their
arms rather than legs, arm-onset patients typically spreads to the legs
before the bulbar region, and leg-onset patients typically spread to the
arms rather than the bulbar region.
Over time, regardless of where symptoms began, most people eventually
lose the ability to walk or use their hands and arms independently. Less
consistently, they may lose the ability to speak and to swallow food.
It is the eventual development of weakness of the respiratory muscles,
with the loss of ability to cough and to breathe without support, that
is ultimately life-shortening in ALS.
The rate of progression can be measured using the ALS Functional Rating Scale - Revised
(ALSFRS-R), a 12-item instrument survey administered as a clinical
interview or self-reported questionnaire that produces a score between
48 (normal function) and 0 (severe disability). The ALSFRS-R is the most frequently used outcome measure in clinical trials and is used by doctors to track disease progression.
Though the degree of variability is high and a small percentage of
people have a much slower progression, on average people with ALS lose
about 1 ALSFRS-R point per month.
Brief periods of stabilization ("plateaus") and even small reversals in
ALSFRS-R score are not uncommon, due to the fact the tool is
subjective, can be affected by medication, and different forms of
compensation for changes in function.
However it is rare (<1%) for these improvements to be large (i.e.
greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12
months).
A survey-based study among clinicians showed that they rated a 20%
change in the slope of the ALSFRS-R as being clinically meaningful,
which is the most common threshold used to determine whether a new
treatment is working in clinical trials.
Late stage disease management
Difficulties with chewing and swallowing make eating very difficult (dysphagia) and increase the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia
can develop, and maintaining a healthy weight can become a significant
problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity
and inspiratory pressure diminish. In respiratory-onset ALS, this may
occur before significant limb weakness is apparent. Individuals affected
by the disorder may ultimately lose the ability to initiate and control
all voluntary movement, known as locked-in syndrome. Bladder and bowel function are usually spared, meaning urinary and fecal incontinence are uncommon, although trouble getting to a toilet can lead to difficulties. The extraocular muscles responsible for eye movement are usually spared, meaning the use of eye tracking technology to support augmentative communication is often feasible, albeit slow, and needs may change over time. Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life.
Prognosis, staging, and survival
Although respiratory support using non-invasive ventilation can ease problems with breathing and prolong survival, it does not affect the progression rate of ALS. Most people with ALS die between two and four years after the diagnosis. Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years, and about 10% survive for 10 years or longer.
The most common cause of death among people with ALS is respiratory failure, often accelerated by pneumonia.
Most ALS patients die at home after a period of worsening difficulty
breathing, a decline in their nutritional status, or a rapid worsening
of symptoms. Sudden death or acute respiratory distress are uncommon. Access to palliative care
is recommended from an early stage to explore options, ensure
psychosocial support for the patient and caregivers, and to discuss advance healthcare directives.
As with cancer staging, ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials.
Two very similar staging systems emerged around a similar time, the
King's staging system and Milano-Torino (MiToS) functional staging.
Kings ALS staging system and prognosis at each stage
Stage 1
Stage 2
Stage 3
Stage 4
Stage description
Symptom onset, involvement of the first region
2A: Diagnosis
2B: Involvement of the second region
Involvement of the third region
4A: Need for a feeding tube
4B: Need for non-invasive ventilation
Median time to stage
13.5 months
17.7 months
23.3 months
4A: 17.7 months
4B: 30.3 months
MiToS ALS staging system and prognosis at each stage
Stage 0
Stage 1
Stage 2
Stage 3
Stage 4
Stage 5
Stage description
No loss of a functional domain
Loss of 1 domain
Loss of 2 domains
Loss of 3 domains
Loss of 4 domains
Death
Probability of death at each stage
7%
26%
33%
33%
86%
Providing individual patients with a precise prognosis is not
currently possible, though research is underway to provide statistical
models on the basis of prognostic factors including age at onset,
progression rate, site of onset, and presence of frontotemporal dementia.
Those with a bulbar onset have a worse prognosis than limb-onset ALS; a
population-based study found that bulbar-onset ALS patients had a
median survival of 2.0 years and a 10-year survival rate of 3%, while
limb-onset ALS patients had a median survival of 2.6 years and a 10-year
survival rate of 13%. Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years. While astrophysicistStephen Hawking lived for 55 more years following his diagnosis, his was an unusual case.
Cognitive, emotional, and behavioral symptoms
Cognitive impairment or behavioral dysfunction is present in 30–50% of individuals with ALS, and can appear more frequently in later stages of the disease. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS. Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms, family history of ALS, and/or a predominantly upper motor neuron phenotype.
Emotional lability
is a symptom in which patients cry, smile, yawn, or laugh, either in
the absence of emotional stimuli, or when they are feeling the opposite
emotion to that being expressed; it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS.
While relatively benign relative to other symptoms, it can cause
increased stigma and social isolation as people around the patient
struggle to react appropriately to what can be frequent and
inappropriate outbursts in public.
In addition to mild changes in cognition that may only emerge
during neuropsychological testing, around 10–15% of individuals have
signs of frontotemporal dementia (FTD). Repeating phrases or gestures, apathy, and loss of inhibition are the most frequently reported behavioral features of ALS. ALS and frontotemporal dementia
(FTD) are now considered to be part of a common disease spectrum
(ALS–FTD) because of genetic, clinical, and pathological similarities. Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of genetic FTD.
Cognitive and behavioral issues are associated with poorer
prognosis as they may reduce adherence to medical advice, and deficits
in empathy and social cognition which may increase caregiver burden.
Cause
It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance.
The genetic factors are better understood than the environmental
factors; no specific environmental factor has been definitively shown to
cause ALS. A multi-step liability threshold model
for ALS proposes that cellular damage accumulates over time due to
genetic factors present at birth and exposure to environmental risks
throughout life. ALS can strike at any age, but its likelihood increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but this difference in sex distribution is no longer present in patients with onset after age 70.
While they appear identical clinically and pathologically,
ALS can be classified as being either familial or sporadic, depending
on whether there is a known family history of the disease and/or whether
an ALS-associated genetic mutation has been identified via genetic
testing. Familial ALS is thought to account for 10-15% of cases overall and can include monogenic, oligogenic, and polygenic modes of inheritance.
There is considerable variation among clinicians on how to
approach genetic testing in ALS, and only about half discuss the
possibility of genetic inheritance with their patients, particularly if
there is no discernible family history of the disease. In the past, genetic counseling and testing was only offered to those with obviously familial ALS. But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing de novo mutations in SOD1, or C9orf72, an incomplete family history, or incomplete penetrance, meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes.
The lack of positive family history may be caused by lack of historical
records, having a smaller family, older generations dying earlier of
causes other than ALS, genetic non-paternity, and uncertainty over whether certain neuropsychiatric conditions (e.g. frontotemporal dementia, other forms of dementia, suicide, psychosis, schizophrenia) should be considered significant when determining a family history. There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS, particularly as there is now a licensed gene therapy (tofersen)
specifically targeted to carriers of SOD-1 ALS. A shortage of genetic
counselors and limited clinical capacity to see such at-risk individuals
makes this challenging in practice, as does the unequal access to
genetic testing around the world.
More than 40 genes have been associated with ALS, of which four
account for nearly half of familial cases, and around 5% of sporadic
cases: C9orf72 (40% of familial cases, 7% sporadic), SOD1 (12% of familial cases, 1-2% sporadic), FUS (4% of familial cases, 1% sporadic), and TARDBP
(4% of familial cases, 1% sporadic), with the remaining genes mostly
accounting for fewer than 1% of either familial or sporadic cases. ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves.
Environmental and other factors
The
multi-step hypothesis suggests the disease is caused by some
interaction between an individual's genetic risk factors and their
cumulative lifetime of exposures to environmental factors, termed their exposome.
The most consistent lifetime exposures associated with developing ALS
(other than genetic mutations) include heavy metals (e.g. lead and mercury), organic chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women).
Overall these effects are small, with each exposure in isolation only
increasing the likelihood of a very rare condition by a small amount.
For instance an individual's lifetime risk of developing ALS might go
from "1 in 400" without an exposure to between "1 in 300" and "1 in 200"
if they were exposed to heavy metals. A range of other exposures have weaker evidence supporting them and include participation in professional sports, having a lower body mass index, lower educational attainment, manual occupations, military service, exposure to Beta-N-methylamino-L-alanin (BMAA), and viral infections.
Although some personality traits, such as openness, agreeableness and conscientiousness
appear remarkably common among patients with ALS, it remains open
whether personality can increase susceptibility to ALS directly. Instead, genetic factors giving rise to personality might simultaneously predispose people to developing ALS, or
the above personality traits might underlie lifestyle choices which are in turn risk factors for ALS.
The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies
(abnormal aggregations of protein) known as Bunina bodies in the
cytoplasm of motor neurons. In about 97% of people with ALS, the main
component of the inclusion bodies is TDP-43 protein; however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively. Prion-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The glymphatic system may also be involved in the pathogenesis of ALS.
Biochemistry
This figure shows ten proposed disease mechanisms for ALS and the genes associated with them.
It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes.
The genes known to be involved in ALS can be grouped into three general
categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS.
It is thought that misfolded mutant SOD1 can cause misfolding and
aggregation of wild-type SOD1 in neighboring neurons in a prion-like
manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1, PFN1, and TUBA4A.
There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm.
Once these mutant RNA-binding proteins are misfolded and aggregated,
they may be able to misfold normal proteins both within and between
cells in a prion-like manner.
This also leads to decreased levels of RNA-binding protein in the
nucleus, which may mean that their target RNA transcripts do not undergo
normal processing. Other RNA metabolism genes associated with ALS
include ANG, SETX, and MATR3.
C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over);
people with up to 30 repeats are considered normal, while people with
hundreds or thousands of repeats can have familial ALS, frontotemporal
dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these C9orf72
repeats are deposition of RNA transcripts in the nucleus, translation
of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and
decreased levels of the normal C9orf72 protein.
Mitochondrial bioenergetic dysfunction leading to dysfunctional motor
neuron axonal homeostasis (reduced axonal length and fast axonal
transport of mitochondrial cargo) has been shown to occur in C9orf72-ALS using human induced pluripotent stem cell (iPSC) technologies coupled with CRISPR/Cas9 gene-editing, and human post-mortem spinal cord tissue examination.
Excitotoxicity, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory neurotransmitterglutamate,
is a mechanism thought to be common to all forms of ALS. Motor neurons
are more sensitive to excitotoxicity than other types of neurons because
they have a lower calcium-buffering capacity and a type of glutamate
receptor (the AMPA receptor) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (EAAT2),
which is the main transporter that removes glutamate from the synapse;
this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole,
a drug that modestly prolongs survival in ALS, inhibits glutamate
release from pre-synaptic neurons; however, it is unclear if this
mechanism is responsible for its therapeutic effect.
Diagnosis
An MRI of the brain (axial FLAIR) looking at a person as if from above that shows increased T2 signal as a small white region within the posterior part of the internal capsule around the center of the image, consistent with the diagnosis of ALS
No single test can provide a definite diagnosis of ALS. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the person and a series of tests to rule out other diseases. Physicians obtain the person's full medical history
and usually conduct a neurologic examination at regular intervals to
assess whether signs and symptoms such as muscle weakness, atrophy of
muscles, hyperreflexia, Babinski's sign, and spasticity are worsening. A number of biomarkers are being studied for the condition, but as of 2023 are not in general medical use.
Because
symptoms of ALS can be similar to those of a wide variety of other,
more treatable diseases or disorders, appropriate tests must be
conducted to exclude the possibility of other conditions. One of these
tests is electromyography
(EMG), a special recording technique that detects electrical activity
in muscles. Certain EMG findings can support the diagnosis of ALS.
Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging
(MRI) is often normal in people with early-stage ALS, it can reveal
evidence of other problems that may be causing the symptoms, such as a
spinal cord tumor, multiple sclerosis, a herniated disc in the neck, syringomyelia, or cervical spondylosis.
Based on the person's symptoms and findings from the examination
and from these tests, the physician may order tests on blood and urine
samples to eliminate the possibility of other diseases, as well as
routine laboratory tests. In some cases, for example, if a physician
suspects the person may have a myopathy rather than ALS, a muscle biopsy
may be performed.
ALS must be differentiated from the "ALS mimic syndromes", which
are unrelated disorders that may have a similar presentation and
clinical features to ALS or its variants.
Because the prognosis of ALS and closely related subtypes of motor
neuron disease are generally poor, neurologists may carry out
investigations to evaluate and exclude other diagnostic possibilities.
Disorders of the neuromuscular junction, such as myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome, may also mimic ALS, although this rarely presents diagnostic difficulty over time. Benign fasciculation syndrome and cramp fasciculation syndrome
may also, occasionally, mimic some of the early symptoms of ALS.
Nonetheless, the absence of other neurological features that develop
inexorably with ALS means that, over time, the distinction will not
present any difficulty to the experienced neurologist; where doubt
remains, EMG may be helpful.
Management
There is no cure for ALS.
Management focuses on treating symptoms and providing supportive care,
with the goal of improving quality of life and prolonging survival.
This care is best provided by multidisciplinary teams of healthcare
professionals; attending a multidisciplinary ALS clinic is associated
with longer survival, fewer hospitalizations, and improved quality of
life.
Non-invasive ventilation (NIV) is the main treatment for respiratory failure in ALS.
In people with normal bulbar function, it prolongs survival by about
seven months and improves quality of life. One study found that NIV is
ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression and functional decline continue. It may decrease the quality of life of people with ALS or their caregivers. Invasive ventilation is more commonly used in Japan than in North America or Europe.
A
person with late-stage ALS with a range of assistive technologies to
support movement (power wheelchair), breathing (invasive ventilation),
and communication (eye tracker and computer)
Physical therapy can promote functional independence through an aerobic, range of motion, and stretching exercises. Occupational therapy can assist with activities of daily living through adaptive equipment. Speech therapy can assist people with ALS who have difficulty speaking. Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. The feeding tube is usually inserted by percutaneous endoscopic gastrostomy (PEG). There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life.
Palliative care should begin shortly after someone is diagnosed with ALS.
Discussion of end-of-life issues gives people with ALS time to reflect
on their preferences for end-of-life care and can help avoid unwanted
interventions or procedures. Hospice care can improve symptom management
at the end of life and increases the likelihood of a peaceful death. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
Medications
Disease-slowing treatments
Chemical structure of riluzole, a medication that prolongs survival by 2–3 months
Riluzole has been found to modestly prolong survival by about 2–3 months. It may have a greater survival benefit for those with bulbar-onset ALS. It may work by decreasing release of the excitatory neurotransmitterglutamate from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (asthenia). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis. Riluzole is available as a tablet, liquid, or dissolvable oral film.
Edaravone has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from oxidative stress. The most common side effects are bruising and gait disturbance. Edaravone is available as an intravenous infusion or as an oral suspension.
AMX0035 (Relyvrio) is a combination of sodium phenylbutyrate and taurursodiol, which was shown to prolong the survival of patients by an average of six months. Relyvrio is available as a powder that is dissolved in water then taken by mouth or feeding tube.
Tofersen (Qalsody) is an antisense oligonucleotide that was approved for medical use in the United States in April 2023, for the treatment of SOD1-associated ALS.
In a study of 108 patients with SOD1-associated ALS there was a
non-significant trend towards a slowing of progression, as well as a
significant reduction in neurofilament light chain, a putative ALS biomarker thought to indicate neuronal damage.
A follow-up study and open-label extension suggested that earlier
treatment initiation had a beneficial effect on slowing disease
progression. Tofersen is available as an intrathecal injection into the lumbar cistern at the base of the spine.
Depression can be treated with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, while benzodiazepines can be used for anxiety.
There are no medications to treat cognitive impairment/frontotemporal
dementia (FTD); however, SSRIs and antipsychotics can help treat some of
the symptoms of FTD. Baclofen and tizanidine are the most commonly used oral drugs for treating spasticity; an intrathecal baclofen pump can be used for severe spasticity. Atropine, scopolamine, amitriptyline or glycopyrrolate may be prescribed when people with ALS begin having trouble swallowing their saliva (sialorrhea).
A 2017 review concluded that mexiletine is safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016.
Breathing support
Non-invasive ventilation
Non-invasive ventilation supports breathing with a face or nasal mask connected to a ventilator.
Non-invasive ventilation (NIV) is the primary treatment for respiratory failure in ALS and was the first treatment shown to improve both survival and quality of life.
NIV uses a face or nasal mask connected to a ventilator that provides
intermittent positive pressure to support breathing. Continuous positive
pressure is not recommended for people with ALS because it makes
breathing more difficult. Initially, NIV is used only at night because the first sign of respiratory failure is decreased gas exchange (hypoventilation)
during sleep; symptoms associated with this nocturnal hypoventilation
include interrupted sleep, anxiety, morning headaches, and daytime
fatigue.
As the disease progresses, people with ALS develop shortness of breath
when lying down, during physical activity or talking, and eventually at
rest.
Other symptoms include poor concentration, poor memory, confusion,
respiratory tract infections, and a weak cough. Respiratory failure is
the most common cause of death in ALS.
It is important to monitor the respiratory function of people
with ALS every three months because beginning NIV soon after the start
of respiratory symptoms is associated with increased survival. This
involves asking the person with ALS if they have any respiratory
symptoms and measuring their respiratory function. The most commonly used measurement is upright forced vital capacity
(FVC), but it is a poor detector of early respiratory failure and is
not a good choice for those with bulbar symptoms, as they have
difficulty maintaining a tight seal around the mouthpiece. Measuring FVC
while the person is lying on their back (supine FVC) is a more accurate
measure of diaphragm weakness than upright FVC.
Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of
diaphragm strength that is not affected by bulbar muscle weakness. If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime blood gas analysis to look for hypoxemia (low oxygen in the blood) and hypercapnia (too much carbon dioxide in the blood). If their daytime blood gas analysis is normal, they should then have nocturnal pulse oximetry to look for hypoxemia during sleep.
Non-invasive ventilation prolongs survival longer than riluzole.
A 2006 randomized controlled trial found that NIV prolongs survival by
about 48 days and improves the quality of life; however, it also found
that some people with ALS benefit more from this intervention than
others. For those with normal or only moderately impaired bulbar
function, NIV prolongs survival by about seven months and significantly
improves the quality of life. For those with poor bulbar function, NIV
neither prolongs survival nor improves the quality of life, though it
does improve some sleep-related symptoms.
Despite the clear benefits of NIV, about 25–30% of all people with ALS
are unable to tolerate it, especially those with cognitive impairment or
bulbar dysfunction.
Results from a large 2015 cohort study suggest that NIV may prolong
survival in those with bulbar weakness, so NIV should be offered to all
people with ALS, even if it is likely that they will have difficulty
tolerating it.
Invasive ventilation
Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (tracheostomy) and inserting a tube connected to a ventilator. It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use.
While invasive ventilation prolongs survival, especially for those
younger than 60, it does not treat the underlying neurodegenerative
process. The person with ALS will continue to lose motor function,
making communication increasingly difficult and sometimes leading to locked-in syndrome, in which they are completely paralyzed except for their eye muscles. About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life
but most still consider it to be satisfactory. However, invasive
ventilation imposes a heavy burden on caregivers and may decrease their
quality of life.
Attitudes toward invasive ventilation vary from country to country;
about 30% of people with ALS in Japan choose invasive ventilation,
versus less than 5% in North America and Europe.
Therapy
A man with ALS communicates by pointing to letters and words using a head-mounted laser pointer.
Physical therapy
plays a large role in rehabilitation for individuals with ALS.
Specifically, physical, occupational, and speech therapists can set
goals and promote benefits for individuals with ALS by delaying loss of
strength, maintaining endurance, limiting pain, improving speech and
swallowing, preventing complications, and promoting functional
independence.
Occupational therapy and special equipment such as assistive technology can also enhance people's independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling
can strengthen unaffected muscles, improve cardiovascular health, and
help people fight fatigue and depression. Range of motion and stretching
exercises can help prevent painful spasticity and shortening (contracture) of muscles.
Physical and occupational therapists can recommend exercises that
provide these benefits without overworking muscles because muscle
exhaustion can lead to a worsening of symptoms associated with ALS,
rather than providing help to people with ALS.
They can suggest devices such as ramps, braces, walkers, bathroom
equipment (shower chairs, toilet risers, etc.), and wheelchairs that
help people remain mobile. Occupational therapists can provide or
recommend equipment and adaptations to enable ALS people to retain as
much safety and independence in activities of daily living as possible.
Since respiratory insufficiency is the primary cause of mortality,
physical therapists can help improve respiratory outcomes in people with
ALS by implementing pulmonary physical therapy. This includes
inspiratory muscle training, lung volume recruitment training, and
manual assisted cough therapy aimed at increasing respiratory muscle
strength as well as increasing survival rates.
People with ALS who have difficulty speaking or swallowing may benefit from working with a speech-language pathologist.
These health professionals can teach people adaptive strategies such as
techniques to help them speak louder and more clearly. As ALS
progresses, speech-language pathologists can recommend the use of augmentative and alternative communication
such as voice amplifiers, speech-generating devices (or voice output
communication devices) or low-tech communication techniques such as
head-mounted laser pointers, alphabet boards or yes/no signals.
Nutrition
A gastrostomy tube is placed through the wall of the abdomen into the stomach.
Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life.
Weight loss in ALS is caused by muscle wasting, increased resting
energy expenditure, and decreased food intake. Difficulty swallowing (dysphagia)
develops in about 85% of people with ALS at some point over the course
of their disease, leading to malnutrition and weight loss. It is important to regularly assess the weight and swallowing ability of people with ALS. Initially, dysphagia may be managed by dietary changes and modified swallowing techniques.
Difficulty swallowing liquids usually develops first and can be managed
by switching to thicker liquids like fruit nectar or smoothies, or by
adding fluid thickeners to thin fluids like water and coffee. People
with ALS should eat soft, moist foods, which tend to be easier to
swallow than dry, crumbly, or chewy foods. They should also be instructed on proper head posture during swallowing, which can make swallowing easier. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival.
A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. This can take the form of a gastrostomy tube, in which a tube is placed through the wall of the abdomen into the stomach, or (less commonly) a nasogastric tube, in which a tube is placed through the nose and down the esophagus into the stomach. A gastrostomy tube is more appropriate for long-term use than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers. The feeding tube is usually inserted by a percutaneous endoscopic gastrostomy procedure (PEG).
There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life by sustaining nutrition and medication intake. This makes up for reduced oral food intake,
decreases risk of weight loss and dehydration, and can decrease anxiety
by shortening what can become extended time taken to eat at mealtimes.
End-of-life care
Palliative care,
which relieves symptoms and improves the quality of life without
treating the underlying disease, should begin shortly after someone is
diagnosed with ALS. Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out advance directives indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes. Late in the disease course, difficulty speaking due to muscle weakness (dysarthria) and cognitive dysfunction may impair their ability to communicate their wishes regarding care.
Continued failure to solicit the preferences of the person with ALS may
lead to unplanned and potentially unwanted emergency interventions,
such as invasive ventilation. If people with ALS or their family members
are reluctant to discuss end-of-life issues, it may be useful to use
the introduction of gastrostomy or noninvasive ventilation as an
opportunity to bring up the subject.
Hospice care,
or palliative care at the end of life, is especially important in ALS
because it helps to optimize the management of symptoms and increases
the likelihood of a peaceful death.
It is unclear exactly when the end-of-life phase begins in ALS, but it
is associated with significant difficulty moving, communicating, and, in
some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, less than 1% of the time. Most patients die at home, and in the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.
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.
Estimated prevalence of ALS in the United States by age group, 2012–2015
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.
History
The French neurologist Jean-Martin Charcot coined the term amyotrophic lateral sclerosis in 1874.American baseball player Lou Gehrig. In some countries, especially the United States, ALS is called "Lou Gehrig's disease".
Descriptions of the disease date back to at least 1824 by Charles Bell. In 1850, François-Amilcar Aran
was the first to describe a disorder he named "progressive muscular
atrophy", a form of ALS in which only the lower motor neurons are
affected. In 1869, the connection between the symptoms and the underlying neurological problems were first described by Jean-Martin Charcot, who initially introduced the term amyotrophic lateral sclerosis in his 1874 paper. Flail arm syndrome, a regional variant of ALS, was first described by Alfred Vulpian in 1886. Flail leg syndrome, another regional variant of ALS, was first described by Pierre Marie and his student Patrikios in 1918.
Diagnostic criteria
In the 1950s, electrodiagnostic testing (EMG) and nerve conduction velocity (NCV) testing began to be used to evaluate clinically suspected ALS. In 1969 Edward H. Lambert
published the first EMG/NCS diagnostic criteria for ALS, consisting of
four findings he considered to strongly support the diagnosis.
Since then a number of diagnostic criteria have been developed, which
are mostly in use for research purposes for inclusion/exclusion
criteria, and to stratify patients for analysis in trials. Research
diagnostic criteria for ALS include the "El Escorial" in 1994, revised in 1998. In 2006, the "Awaji" criteria proposed using EMG and NCV tests to help diagnose ALS earlier, and most recently the "Gold Coast" criteria in 2019.
Amyotrophic comes from Greek: a- means "no", myo- (from mûs) refers to "muscle", and trophḗ means "nourishment". Therefore, amyotrophy means "muscle malnourishment" or the wasting of muscle tissue. Lateral identifies the locations in the spinal cord of the affected motor neurons. Sclerosis means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.
ALS is sometimes referred to as Charcot's disease (not to be confused with Charcot–Marie–Tooth disease or Charcot joint disease), because Jean-Martin Charcot was the first to connect the clinical symptoms with the pathology seen at autopsy. The British neurologist Russell Brain coined the term motor neurone disease
in 1933 to reflect his belief that ALS, progressive bulbar palsy, and
progressive muscular atrophy were all different forms of the same
disease. In some countries, especially the United States, ALS is called Lou Gehrig's disease after the American baseball player Lou Gehrig, who developed ALS in 1938.
In the United States and continental Europe, the term ALS (as well as Lou Gehrig's disease in the US) refers to all forms of the disease, including "classical" ALS, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis. In the United Kingdom and Australia, the term motor neurone disease refers to all forms of the disease while ALS only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement.
