Amyotrophic lateral sclerosis (ALS) — Lou Gehrig's disease, and rarely Charcot disease —is a neurodegenerative disorder with various causes. The term motor neuron disease (MND) is sometimes used interchangeably with ALS, while others use it to refer to a group of similar conditions that include ALS. ALS is characterized by muscle spasticity, rapidly progressive weakness due to muscle wasting. This results in difficulty speaking, swallowing, and breathing. The disease usually starts around the age of 60, except in cases that are directly inherited when the usual age of onset is around 50.
About 5 to 10% of cases are directly inherited from a person's parents. ALS is the most common of the five types of motor neuron disease.
The average survival from onset to death is three to four years. Only 4% survive longer than 10 years, although rare cases survive 50 years or more. Most die from respiratory failure. In much of the world rates of ALS are unknown. In Europe the disease affects about 2.2 people per 100,000 per year. In the United States, more than 5,600 are diagnosed every year, and up to 30,000 Americans are currently affected. ALS is responsible for 2 deaths per 100,000 people per year.
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 were first described by Jean-Martin Charcot who in 1874 began using the term amyotrophic lateral sclerosis. It became well known in the United States when it affected a famous baseball player by the name of Lou Gehrig, and later when the ice bucket challenge became popular in 2014.
Signs and symptoms
The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel function and the muscles responsible for eye movement are usually spared until the final stages of the disorder.
Cognitive function is generally spared for most people, although some (about 5%) also develop frontotemporal dementia... A higher proportion of people (30–50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Infrequently ALS coexists in individuals who also experience dementia, degenerative muscle disorder, and degenerative bone disorder as part of a syndrome called multisystem proteinopathy. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS will maintain hearing, sight, touch, smell, and taste.
Initial symptoms
The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include trouble swallowing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/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. About 75% of people contracting the disorder experience "limb onset" ALS, i.e., first symptoms in the arms or legs. People with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a "dropped foot" which drags gently along the ground. Arm-onset people may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.
About 25% of cases are "bulbar onset" ALS. These people first notice difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other symptoms include difficulty 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. A small proportion of people may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms.
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. An abnormal reflex commonly called Babinski's sign also indicates upper motor neuron damage. 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). Around 15–45% of people experience pseudobulbar affect, a neurological disorder also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion. To be diagnosed with ALS, people must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
Progression
Although the order and rate of symptoms varies from person to person, eventually most people are not able to walk or use their hands and arms. They also lose the ability to speak and swallow food, while most end up on a portable ventilator, called a BiPAP. The rate of progression can be measured using an outcome measure called the "ALS Functional Rating Scale Revised (ALSFRS-R)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though there is a high degree of variability and a small percentage of people have much slower disorder, on average, patients lose about 0.9 FRS point per month. A survey-based study amongst clinicians showed that they rated a 20% change in the slope of the ALSFRS-R would be clinically meaningful. Regardless of the part of the body first affected by the disorder, muscle weakness and atrophy spread to other parts of the body as the disorder progresses. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in Bulgar-onset ALS symptoms typically spread to the arms before the legs.
Disorder progression tends to be slower in patients who are younger than 40 at onset, are mildly obese, have disorder restricted primarily to one limb, and those with primarily upper motor neuron symptoms. Conversely, progression is faster and prognosis poorer in people with bulbar-onset disorder, respiratory-onset disorder, and fronto-temporal dementia.
The CX3CR1 allelic variants have also been shown to have an effect on the disorder's progression and on person life expectancy
Late stages
Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years. Guitarist Jason Becker has lived since 1989 with the disorder, while physicist Stephen Hawking has survived for more than 50 years, but they're considered unusual cases.
Difficulty in chewing and swallowing makes eating very difficult and increases 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. Most people with ALS die of respiratory failure or pneumonia.
In late stages the oculomotor nerve that controls the movements of the eye, can be affected as can the extraocular muscles. The eye movements remain unaffected largely until the later stages due to differences in the extraocular muscles compared to the skeletal muscles that are initially and readily affected.
In the disease's final stages, a person's condition may resemble locked-in syndrome.
by Dea