“ALS” redirects here. For other uses, see ALS (disambiguation). “Motor neurone disease” redirects here. For a broader group of diseases that affect motor neurons, see Motor neuron disease. It has been suggested that Extraocular muscles and ALS be merged into this article. (Discuss) Proposed since August 2013. Amyotrophic Lateral Sclerosis Classification and external resources ALS Coronal. jpg.
This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. However, typically MRI imaging is unremarkable in a patient with ALS. ICD-10G12. 2 ICD-9335. 20 OMIM105400 DiseasesDB29148 MedlinePlus000688 eMedicineneuro/14 emerg/24 pmr/10 MeSHD000690.
Amyotrophic lateral sclerosis (ALS) – also referred to as motor neurone disease (MND) in most Commonwealth countries, and as Lou Gehrig’s disease in the United States – is a debilitating disease with varied etiology characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and difficulty breathing (dyspnea). ALS is the most common of the five motor neuron diseases. Contents [hide] 1 Signs and symptoms 1. 1 Initial symptoms.
1. 2 Disease progression and spread 1. 3 Late stage disease symptoms 2 Cause 2. 1 Genetic factors 2. 1. 1 SOD1 2. 2 Other factors 3 Pathophysiology 4 Diagnosis 5 Treatment 5. 1 Slowing progression 5. 2 Disease management 5. 2. 1 Pharmaceutical treatments 5. 2. 2 Physical, occupational and speech therapy 5. 2. 3 Feeding and nutrition 5. 2. 4 Breathing support 5. 2. 5 Palliative care 6 Epidemiology 7 Etymology 8 History 9 Clinical research 10 See also 11 References 12 Further reading 13 External links Signs and symptoms[edit].
The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and exhibit atrophy. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared until the terminal stages of the disease. [1] Cognitive function is generally spared for most patients, although some (about 5%) also have frontotemporal dementia.
[2] A higher proportion of patients (30–50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. 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[edit] The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), 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 disease experience “limb onset” ALS, i. e. , first symptoms in the arms or legs. Patients 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 patients 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 patients 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 patients experience “respiratory onset” ALS, where the intercostal muscles that support breathing are affected first.
A small proportion of patients may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms. Over time, patients 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 patients experience pseudobulbar affect, 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. [citation needed] To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
Disease progression and spread[edit] Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk or use their hands and arms. They also lose the ability to speak and swallow their food, whilst most end on a portable ventilator, called BPAP. 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 patients have much slower disease, on average, patients lose about 0. 9 FRS point per month. A study amongst clinicians showed that they rated a 20% change in the slope of the ALSFRS-R would be clinically meaningful. [3] Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses.
In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS symptoms typically spread to the arms before the legs. Disease progression tends to be slower in patients who are younger than 40 at onset,[4] have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms. [5] Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia. [5] Late stage disease symptoms[edit].
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 disease, 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.
External ventilation machines that use the ventilation mode of bilevel positive airway pressure (BPAP) are frequently used to support breathing, initially at night, and later during the daytime as well. The use of BPAP (more often referred to as non-invasive ventilation, NIV) is only a temporary remedy, however, and it is recommended that long before BPAP stops being effective, patients should decide whether to have a tracheotomy and long term mechanical ventilation. At this point, some patients choose palliative hospice care. Most people with ALS die of respiratory failure or pneumonia.
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. [6] Physicist Stephen Hawking has lived with the disease for more than 50 years, though he is an unusual case. [7] Cause[edit] Genetic factors[edit] There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families.
A defect on chromosome 21, which codes for superoxide dismutase, is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall. [8][9][10] This mutation is believed to be transmitted in an autosomal dominant manner, and has over a hundred different forms of mutation. The most common ALS-causing SOD1 mutation in North American patients is A4V, characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A, is more slowly progressive than typical ALS and patients with this form of the disease survive for an average of 11 years. [11].