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. most cases of als, however, are correctly diagnosed, with the error rate of diagnosis in large als clinics being less than 10%. one study examined 190 people who met the mnd/als diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. thirty of these people (16%) had their diagnosis completely changed during the clinical observation development period. in the same study, three people had a false negative diagnosis of mg, which can mimic als and other neurological disorders, leading to a delay in diagnosis and treatment. mg is eminently treatable; als is not. 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. riluzole prolongs survival by about 2–3 months. edaravone slows functional decline slightly in a small number of people with als; it is expensive and must be administered by daily iv infusions that may decrease quality of life. other medications may be used to manage other symptoms. 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. 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 neurotransmitter glutamate 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, a combination of sodium phenylbutyrate and taurursodiol, was shown to prolong the survival of patients by an average of six months. 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 35%+50% reduction in the putative als biomarker neurofilament light chain, 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 injection into the spinal cord. symptomatic treatments other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. gabapentin, pregabalin, and tricyclic antidepressants (e.g., amitriptyline) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (nsaids), acetaminophen, and opioids can be used for nociceptive pain. 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. 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