The hallmark of the disease is a mixed upper and lower motor neuropathy that is progressive over time. The upper motor signs include spasticity, hyperreflexia and weakness. The lower motor signs include amyotrophy, weakness and fasciculations. The diagnosis is suspected when there is insidious loss of function in more than one parts of the body. The lower motor neuron signs tend to appear first usually in the tongue and limbs. 80% of patients present with predominately limb symptoms with the rest presenting with bulbar symptoms.

The limb disease may present with altered gate such a foot drag while upper limb involvement usually begins with loss of dexterity and wasting of muscles over time. Eventually the function deteriorates and mobility reduces with spasticity and subsequent contractures.

Patients who present with bulbar symptoms usually present with speech abnormalities and dysphagia. Most patient will tend to preserve ocular movements and bladder control [9].

• Weakness

  Symptoms vary in severity and may include muscle weakness and atrophy, fasciculations, emotional lability, and respiratory muscle weakness. [msdmanuals.com]

  Muscle weakness can have many causes. [merckmanuals.com]

  Over a period of months or years, ALS causes increasing muscle weakness, inability to control movement, and problems with speaking, swallowing, and breathing. The cause of ALS is unknown, and there is no cure. [stanfordhealthcare.org]

  In 1997, a 68-year-old woman noted weakness in the hands. When she was first seen in November 1997, she had amyotrophy of the hands. Distal motor weakness of the upper limbs was graded 2. Fasciculations were present in the 4 limbs and the tongue. [dx.doi.org]

  Table 2 Fasciculation potential parameters in weak and non-weak muscles in amyotrophic lateral sclerosis Measurement Muscle weakness No muscle weakness P * Median (range) Median (range) n 166 264 Amplitude (mV) 0.38 (0.04–2.21) 0.41 (0.034–10.01) NS Area [doi.org]

• Pain

  The site of pain depends on the pain type or underlying mechanism (eg, painful cramps, nociceptive pain, or neuropathic pain). [ncbi.nlm.nih.gov]

  If pain develops as the disease progresses (for example, if pain occurs when a person has to sit in one position too long), benzodiazepines, which are mild sedatives, may be used. [merckmanuals.com]

  Effects of self-hypnosis training and cognitive restructuring on daily pain intensity and catastrophizing in individuals with multiple sclerosis and chronic pain. Int. J. Clin. Exp. Hypn. 59, 45–63. [journal.frontiersin.org]

• Fatigue

  All studies assessed fatigue using the Fatigue Severity Scale (FSS; scale from 9 to 63, higher scores indicate more fatigue). [ncbi.nlm.nih.gov]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

  Typical Presentation: Gradual onset, progressive muscle failure weakness, fatigue, problems with swallowing, abnormal reflexes, cramping, fasciculations [athenadiagnostics.com]

• Weight Loss

  ALS with respiratory onset has some common clinical features: male predominance, frequent camptocormia or dropped head, frequent widespread fasciculations, limb mobility fairly well preserved and significant weight loss in the early stages. [ncbi.nlm.nih.gov]

  Other symptoms include: Difficulty breathing Difficulty swallowing Muscle cramps and weakness Speech problems Voice changes Weight loss Diagnosis ALS is diagnosed through a combination of physical exams and medical tests, including blood tests, breathing [mercyhealth.com]

  Complications of ALS include: Breathing in food or fluid ( aspiration ) Loss of ability to care for self Lung failure Pneumonia Pressure sores Weight loss Call your provider if: You have symptoms of ALS, particularly if you have a family history of the [nlm.nih.gov]

• Nocturnal Leg Cramp

  FDA bans quinine for nocturnal leg cramps. Drug Utilization Rev. 1995; Oct:150. 26. Moss AH, Casey P, Stocking CB, Roos RP, Brooks BR, Siegler M. [aafp.org]

  […] during the night and predominantly affect the lower limbs, then referred to as nocturnal leg muscle cramps. [dovepress.com]

• Dyspnea

  CASE PRESENTATION: A 65-year-old Caucasian man with advanced amyotrophic lateral sclerosis presented with progressive dyspnea and palpitations. [ncbi.nlm.nih.gov]

  Dyspnoea was evaluated using the Multidimensional Dyspnea Profile. Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. [erj.ersjournals.com]

  As the disease progresses the patient has difficulty swallowing and talking, with dyspnea as the accessory muscles of respiration are affected. Eventually muscles atrophy and the patient becomes a functional quadriplegic. [medical-dictionary.thefreedictionary.com]

• Hoarseness

  […] climbing stairs, and walking Difficulty breathing Difficulty swallowing -- choking easily, drooling, or gagging Head drop due to weakness of the neck muscles Speech problems, such as a slow or abnormal speech pattern (slurring of words) Voice changes, hoarseness [nlm.nih.gov]

  The voice usually sounds nasal but may be hoarse. As symptoms progress, people may be unable to control emotional responses and may laugh or cry inappropriately. Eventually, the muscles involved in breathing weaken, leading to breathing problems. [merckmanuals.com]

  Damage to the medulla can cause: slurred speech hoarseness difficulty swallowing emotional lability, which is characterized by excessive emotional reactions such as laughing or crying a loss of tongue muscle contour, or tongue atrophy excess saliva difficulty [healthline.com]

• Dry Cough

  If patients report dry cough, this should prompt further diagnostic steps. [doi.org]

• Stridor

  This case demonstrates that this occurs because amyotrophic lateral sclerosis patients' upper motor neuron reflex laryngeal closure and stridor cause upper airway collapse that renders mechanical insufflation-exsufflation (MIE) ineffective in expulsing [ncbi.nlm.nih.gov]

• Dysphagia

  BACKGROUND: Dysphagia is a critical symptom of Neuromuscular Diseases and is often associated with considerable morbidity and mortality. [ncbi.nlm.nih.gov]

  Her husband was 73 years old when he noted dysphagia in 1999. Deep tendon reflexes were brisk in the 4 limbs with diffuse fasciculations and amyotrophy. [dx.doi.org]

  Symptoms include progressive weakness, atrophy, fasciculation, dysphagia, and eventual paralysis of respiratory function. [patientslikeme.com]

• Dysphagia

  BACKGROUND: Dysphagia is a critical symptom of Neuromuscular Diseases and is often associated with considerable morbidity and mortality. [ncbi.nlm.nih.gov]

  Her husband was 73 years old when he noted dysphagia in 1999. Deep tendon reflexes were brisk in the 4 limbs with diffuse fasciculations and amyotrophy. [dx.doi.org]

  Symptoms include progressive weakness, atrophy, fasciculation, dysphagia, and eventual paralysis of respiratory function. [patientslikeme.com]

• Choking

  Nurses or other caregivers must feed people with swallowing difficulties carefully to prevent choking. Some people must be fed through a tube inserted through the abdominal wall into the stomach ( gastrostomy tube ). [merckmanuals.com]

  You'll start to have trouble swallowing and may choke on liquids or drool. Your voice may not sound right. Muscles that aren't used start to shrink and tighten up. You may first notice shrinking in the muscles of your hands. [msdmanuals.com]

  Choking - lorazepam sublingually can quickly relieve choking episodes. Dyspnoea - if severe and prolonged, is an indication for subcutaneous morphine. Complications Respiratory failure and death. Pneumonia due to infection or aspiration. [patient.info]

• Gagging

  Muscle weakness starts in one body part, such as the arm or hand, and slowly gets worse until it leads to the following: Difficulty lifting, climbing stairs, and walking Difficulty breathing Difficulty swallowing -- choking easily, drooling, or gagging [nlm.nih.gov]

  Speech is spastic, patients cannot rapidly repeat syllables, (kakaka, tatata, lalala, bababa); gag reflex and jaw jerk are brisk. A pseudobulbar affect with emotional lability may also occur. [msdmanuals.com]

• Sialorrhea

  Antisialorrhea agents Sialorrhea, or drooling, is embarrassing and is associated with aspiration pneumonia. The prevalence for patients with ALS is 50%. [emedicine.com]

  Evidence regarding secondary symptoms like spasticity, muscle cramps or sialorrhea remains generally scarce, but some new insights will also be discussed. Growing evidence suggests that multidisciplinary care in specialized clinics improves survival. [ncbi.nlm.nih.gov]

  Sialorrhea and bronchial secretions Due to progressive weakness of pharyngeal muscles and reduced swallowing capability, sialorrhea is a common problem in ALS, increasing the risk of aspiration and preventing effective use of noninvasive ventilation. [doi.org]

• Fasciculation of the Tongue

  In July 1995, she had amyotrophy and fasciculations of the tongue together with an exaggeration of the gag reflex. She had weakness of the cervical spine muscles and fasciculations of the upper limbs. [dx.doi.org]

  Bulbar onset: The first sign is usually slurring of the speech (impaired tongue movement). Wasting and fasciculation of the tongue. Dysphagia (usually a late feature with significant speech difficulties). [patient.info]

  Within a month, the patient had slurred speech, difficulty in swallowing liquids and fasciculations of the tongue. [aafp.org]

• Tongue Atrophy

  Damage to the medulla can cause: slurred speech hoarseness difficulty swallowing emotional lability, which is characterized by excessive emotional reactions such as laughing or crying a loss of tongue muscle contour, or tongue atrophy excess saliva difficulty [healthline.com]

  atrophy on upper airway patency. [dovepress.com]

• Muscular Atrophy

  […] lateral sclerosis G12.24 Familial motor neuron disease G12.25 Progressive spinal muscle atrophy G12.29 Other motor neuron disease G12.8 Other spinal muscular atrophies and related syndromes G12.9 Spinal muscular atrophy, unspecified G13 Systemic atrophies [icd10data.com]

  Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. [ncbi.nlm.nih.gov]

  Pyramidal signs and muscle atrophy - Characteristically in ALS, the signals of pyramidal release must be present at sites above the sites where the muscular atrophy is evident. [doi.org]

• Muscle Cramp

  There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. [ncbi.nlm.nih.gov]

  Studies directly addressing muscle cramps in ALS should assess number and duration of muscle cramps as well as intensity of muscle cramps on a VAS. [doi.org]

  cramping urinary frequency or incontinence (late findings) sensory remains normal Physical exam neck ptosis (neck drop) due to neck extensor weakness manual muscle testing elicits muscle cramping upper motor neuron (UMN) signs spasticity hyperreflexia [orthobullets.com]

  Other symptoms include: Difficulty breathing Difficulty swallowing Muscle cramps and weakness Speech problems Voice changes Weight loss Diagnosis ALS is diagnosed through a combination of physical exams and medical tests, including blood tests, breathing [mercyhealth.com]

• Muscle Twitch

  twitching for 3 years. [ncbi.nlm.nih.gov]

  Benign muscle twitches quickly become Lou Gehrig's disease and the person's anxiety escalates as quickly as the search engine spits out new results. The malady is now called Lou Gehrig's Disease. [fi.bab.la]

  Muscles twitch (called fasciculations). Muscle tone typically increases, and muscles tend to become stiff and tight, leading to muscle spasms (called spasticity). Movements are stiff and clumsy. [merckmanuals.com]

  Clinical Signs, Symptoms, and Diagnostics Symptoms and signs associated with these pathological changes include: Muscle fasciculation, more commonly known as muscle twitches Difficulty walking, moving your arms, speaking, and swallowing And, eventually [study.com]

  Symptoms of ALS include progressive muscle weakness beginning in the limbs, muscle twitching and cramping, slowed speech becoming progressively harder to understand, difficulty in breathing and swallowing; persistent fatigue, weight loss resulting from [brainfoundation.org.au]

• Muscle Spasticity

  This is a progressive and fatal disease, with initial complaints about muscle spasticity followed by progressively worsening muscle weakness. [fusfoundation.org]

  Also known as Lou Gehrig’s disease in the US and motor neuron disease in the UK, ALS is characterized both by muscle spasticity and a progressive weakening of the muscles. [youtube.com]

  Doctors can prescribe medications for reducing fatigue, muscle cramps, muscle spasticity, and excessive saliva or phlegm, as well as pain, depression, sleeping problems or constipation. ALS affects the breathing muscles, particularly the diaphragm. [livescience.com]

  spasticity and stiffness, and modest muscle atrophy.1 PLS cannot be diagnosed as ALS until there is evidence of LMN dysfunction of at least 1 limb or region and it progresses to ALS in most patients.30 Limb-onset ALS is also known as flail leg or flail [ajmc.com]

• Muscle Spasm

  Baclofen may reduce muscle spasms. Nuedexta might help keep emotions in check ( pseudobulbar affect ). Mexiletine might reduce painful muscle cramps. A number of medicines including Robinul, Elavil, and Botox, may help reduce salivation. [alstdi.org]

  As the muscles lose strength, some people experience muscle cramps, twitches, or spasms. [chealth.canoe.com]

• Mood Swings

  The following symptoms are common: Apathy (lack of interest, withdrawal) Lack of emotion Reduced spontaneity Loss of inhibition Restlessness or overactivity Social inappropriateness Mood swings Cognitive symptoms include the following: Memory loss Loss [emedicinehealth.com]

• Dysarthria

  Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria [ncbi.nlm.nih.gov]

• Slurred Speech

  speech, stumbling, and muscle twitching for 3 years. [ncbi.nlm.nih.gov]

  ALS often begins with muscle twitching and weakness in a limb, or slurred speech. Eventually, ALS affects control of the muscles needed to move, speak, eat and breathe. There is no cure for this fatal disease. [mayoclinic.org]

  The earliest symptoms of Lou Gehrig's Disease may include: Tripping and falling Hand weakness or clumsiness Weakness in your leg, feet or ankles Slurred speech or trouble swallowing Difficulty walking or doing your normal daily activities Difficulty holding [disabled-world.com]

  Other early symptoms vary but can include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches, and/or uncontrollable periods of laughing or crying. [alsa.org]

  Sometimes the initial problem can be one of slurred speech or difficulty swallowing. As ALS progresses, though, more and more symptoms are noticed. The following are the most common symptoms of ALS. [columbianeurology.org]

• Clumsiness

  Typically, muscles are weak and waste away, and movements become stiff, clumsy, and awkward. [merckmanuals.com]

  […] extensor weakness manual muscle testing elicits muscle cramping upper motor neuron (UMN) signs spasticity hyperreflexia (+) Hoffman's (+) Babinski's spastic dysarthria lower motor neuron (LMN) signs muscular atrophy weakness clinical fasciculations clumsiness [orthobullets.com]

  The earliest symptoms of Lou Gehrig's Disease may include: Tripping and falling Hand weakness or clumsiness Weakness in your leg, feet or ankles Slurred speech or trouble swallowing Difficulty walking or doing your normal daily activities Difficulty holding [disabled-world.com]

  Generally, symptoms consist of stiffness, clumsiness, and awkward movements, usually affecting first the mouth, throat, or both, then spreading to the limbs. [msdmanuals.com]

• Ataxia

  Blood from ND patients with PD, ALS and Ataxia with movement dysfunctions were obtained to analyse mRNA and protein expressions of the above mentioned factors in lymphocytes. [ncbi.nlm.nih.gov]

  Gluten-associated ataxia had already been linked to the presence of serum transglutaminase 6 antibodies; these had been reported to be present in 62% of patients with gluten ataxia. [brainblogger.com]

  G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia, unspecified G12 Spinal muscular atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type [icd10data.com]

• Hyperreflexia

  […] and positive waves) + decreased recruitment in ≥ 3 extremities reinnervation abnormal spontaneous fibrillation & fasciculation potentials normal sensory studies (SNAP, sensory nerve action potentials) Differentials Peripheral compressive neuropathy hyperreflexia [orthobullets.com]

  If upper motor neurons are also damaged, spasticity and hyperreflexia and pathologic reflexes, such as Babinski’s sign, can also be observed. Inevitably, ALS progresses over time. [flexikon.doccheck.com]

  The upper motor signs include spasticity, hyperreflexia and weakness. The lower motor signs include amyotrophy, weakness and fasciculations. The diagnosis is suspected when there is insidious loss of function in more than one parts of the body. [symptoma.com]

  The diagnostic process consists of a history and physical examination, repeated at regular intervals, to document progressive hyperreflexia, fasciculations, and upper and lower motor neuron involvement. [aafp.org]

Due to it slow progression it may take a neurologist a few months to come to a diagnosis, unless there is a strong family history of the illness. Needle electromyography and nerve conduction studies and will aid in diagnosis and exclude any other conditions that may mimic the disease. Genetic testing is only performed if there is a suspicion that there may be a genetic or familial cause. If there is uncertainty a muscle biopsy may have to be done to exclude other courses.

The treatment for this condition is totally supportive and includes, speech, physical and occupational therapy. It is very important that the patient and relatives are educated well on the condition and prognosis. There are also a number of support groups that help families and suffers deal with the condition. The only drug available currently is riluzole that has been shown to delay the time to tracheostomy by about 2 months [10].

As mentioned before, amyotrophic lateral sclerosis is a fatal disease with the median time to death from diagnosis being 3 years. The patients who survive long tend to get the disease at a younger age, with primary limb involvement. Most individuals succumb to secondary infections such a pneumonia [8].

The underlying etiology is unknown. Most cases are sporadic with approximately 10% of the cases being familial or genetic. The genes in familial causes are numerous and no single gene has been identified that can explain the pathology. Many of the genes identified have been associated with other neurological diseases such as dementia and Alzheimer disease. In the families which have identified genes the mode of transmission is usually autosomal dominant. There is no clinical difference between the familial variant compared to the sporadic cases.

The only establish risk factor that has been identified is smoking. Studies have shown that smokers are at twice the risk of suffering from this disease as compared to non-smokers [2] [3].

The annual incidence is approximately 2 per 100,000 population. Finland has the highest incidence in the world with rates almost twice that of other countries. It tends to affect whites more than other races and is higher in men as compared to women.
Amyotrophic lateral sclerosis may occur between teenager years to as high as the 80s. There is increasing risk with age [4] [5] [6].

The pathophysiology of amyotrophic lateral sclerosis is unknown, but a number of theories exist. The disease is named after the pathology is causes - amyotrophy - muscular atrophy, and lateral sclerosis refers to the changes seen in the lateral tracts.

It is thought that there are multiple mechanisms involved, few which have been noted include derangements in free radical scavenging, and derangements in cellular cytoskeletons. The most upcoming theory that has a lot of research focused on it is the theory that aggregation in mRNA processing may be a significant contributor, leading to neuronal dysfunction and death [7].

The only risk factor identified is smoking so cessation or avoidance would assume to be beneficial. Suspected family cases should have testing and counselling when appropriate.

Amyotrophic lateral sclerosis (ALS) is overall a fatal disease with no active treatments. With good support, suffers may lead meaningful, but restricted lives. It is one of many motor neuron diseases, but what makes it stand out is that it presents with both upper and lower motor neuron signs [1].

• Definition: Amyotrophic lateral sclerosis (ALS) is a disease that affects the nerves that control muscle movement. This causes the muscles to weaken and become shrunken. This makes it difficult for the person to do daily activates and eventually they may be unable to walk, talk or eat as the disease progresses. 
• Cause: The cause of this disease is unknown, but there are some families that are known to pass it down generations. In these families a few genes have been affected. Most of the cases have no family links. There has been some information that smoking may contribute to its onset.
• Symptoms: The will be weakness of the affected region of the body, with either rigid limbs or floppy limbs. Speech and swallowing may be the first to be affected in some individuals. 
• Diagnosis: Most of the diagnosis is made by history and examination, with few tests being done to see if the nerves are functioning well.
• Treatment: Treatment is very limited with only one drug available called riluzole that slows down the disease, briefly. Most of the other treatment is supportive to help the patient not to get stiffness in the joints and bedsores. They may require speech therapy and devices to aid in movement such as wheel chairs. As speech is also affected communication devices may be required to aid. They may also require breathing support and feeding tubes. 
• Overall the disease has a poor outcome and family support is very important. There are groups that aid the families psychologically, helping them understand and process all the information.

1. Mitsumoto H, Chad DA, Pioro EP. Amyotrophic lateral sclerosis. In: Contemporary Neurology Series, 49, F.A. Davis Company, Philadelphia 1998.
2. l-Chalabi A, Lewis CM. Modelling the effects of penetrance and family size on rates of sporadic and familial disease. Hum Hered. 2011;71(4):281-8. 
3. Hanby MF, Scott KM, Scotton W, Wijesekera L, Mole T, Ellis CE, et al. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis. Brain. Dec 2011;134:3454-7. 
4. Chiò A, Mora G, Calvo A, Mazzini L, Bottacchi E, Mutani R. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology. Feb 24 2009;72(8):725-31. 
5. Alonso A, Logroscino G, Jick SS, Hernán MA. Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study. Eur J Neurol. Jun 2009;16(6):745-51.
6. Johnston CA, Stanton BR, Turner MR, Gray R, Blunt AH, Butt D, et al. Amyotrophic lateral sclerosis in an urban setting: a population based study of inner city London. J Neurol. Dec 2006;253(12):1642-3.
7. Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic Biol Med. Mar 1 2010;48(5):629-41
8. Visser J, van den Berg-Vos RM, Franssen H, et al. Disease course and prognostic factors of progressive muscular atrophy. Arch Neurol 2007; 64:522.
9. Hirano A. Neuropathology of ALS: an overview. Neurology 1996; 47:S63.
10. Miller RG, Jackson CE, Kasarskis EJ et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1218-1226