The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor 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 extraocular muscles (the muscles responsible for eye movement) are usually spared until the final stages of the disease. Cognitive or behavioral dysfunction is present in 30–50% of individuals with<unk> . Around half of people with<unk>  will experience mild changes in cognition and behavior, and 10–15% will show signs of frontotemporal dementia (FTD). Most people with<unk>  who have normal cognition at the time of diagnosis have preserved cognition throughout the course of their disease; the development of cognitive impairment in those with normal cognition at baseline is associated with a worse prognosis. Repeating phrases or gestures, apathy, and loss of inhibition are frequently reported behavioral features of<unk> . Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in<unk> ; a meta-analysis found no relationship between dysfunction and disease severity. However, cognitive and behavioral dysfunctions have been found to correlate with reduced survival in people with<unk>  and increased caregiver burden; this may be due in part to deficits in social cognition. About half the people who have<unk>  experience emotional lability, in which they cry or laugh for no reason; it is more common in those with bulbar-onset<unk> . Pain is a symptom experienced by most people with<unk>  and can take the form of neuropathic pain (pain caused by nerve damage), spasticity, muscle cramps, and nociceptive pain caused by reduced mobility and muscle weakness; examples of nociceptive pain in<unk>  include contractures (permanent shortening of a muscle or joint), neck pain, back pain, shoulder pain, and pressure ulcers. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with<unk>  maintain hearing, sight, touch, smell, and taste. Initial symptoms The start of<unk>  may be so subtle that the symptoms are overlooked. The earliest symptoms of<unk>  are muscle weakness or muscle atrophy. 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<unk>  depend on which motor neurons in the body are damaged first. In limb-onset<unk> , 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<unk> , 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"<unk> , 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. An abnormal reflex commonly called Babinski's sign<unk> o 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). However, twitching is more of a side effect than a diagnostic symptom; it either occurs after or accompanies weakness and atrophy. Progression Although the initial symptoms and rate of progression vary from person to person, the disease eventually spreads to unaffected regions and the affected regions become more affected. Most people eventually are not able to walk or use their hands and arms, lose the ability to speak and swallow food and their own saliva, and begin to lose the ability to cough and to breathe on their own. The rate of progression can be measured using the<unk>  Functional Rating Scale - Revised <unk> FRS-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); it is the most commonly 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 disorder, on average, people with<unk>  lose about 0.9 FRS points per month. A survey-based study among clinicians showed that they rated a 20% change in the slope of the<unk> FRS-R as being clinically meaningful. Disease progression tends to be slower in people who are younger than 40 at onset, are mildly obese, have symptoms 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<unk> , respiratory-onset<unk>  and frontotemporal dementia. Late stages Difficulties with chewing and swallowing make eating very difficult 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<unk> , this may occur before significant limb weakness is apparent. The most common cause of death among people with<unk>  are respiratory failure or pneumonia and most people with<unk>  die in their own home from the former cause, with their breath stopping while they sleep. Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of<unk> . Most people with<unk>  die between two and four years after the diagnosis. Around half of people with<unk>  die within 30 months of their symptoms beginning, and about 20% of people with<unk>  live between five and ten years after symptoms begin. Guitarist Jason Becker has lived since 1989 with the disorder, while cosmologist Stephen Hawking lived for 55 more years following his diagnosis, but they are considered unusual cases.
Amyotrophic lateral sclerosis
Botulism
Tropical ataxic neuropathy
Juvenile primary lateral sclerosis
Vascular myelopathy
Multiple system atrophy
Surfer's myelopathy
Lambert–Eaton myasthenic syndrome