In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the "absence" of:

- brisk reflexes

- spasticity

- Babinski's sign

- Emotional lability

As a result of lower motor neurone degeneration, the symptoms of PMA include:

- atrophy

- fasciculations

- muscle weakness

Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.

Onset of PLS usually occurs spontaneously after age 50 and progresses gradually over a number of years, or even decades. The disorder usually begins in the legs, but it may start in the tongue or the hands. Symptoms may include difficulty with balance, weakness and stiffness in the legs, and clumsiness. Other common symptoms are spasticity (involuntary muscle contraction due to the stretching of muscle, which depends on the velocity of the stretch) in the hands, feet, or legs, foot dragging, and speech and swallowing problems due to involvement of the facial muscles. Breathing may also become compromised in the later stages of the disease, causing those patients who develop ventilatory failure to require noninvasive ventilatory support. Hyperreflexia is another key feature of PLS as seen in patients presenting with the Babinski's sign. Some people present with emotional lability and bladder urgency, and occasionally people with PLS experience mild cognitive changes detectable on neuropsychological testing, particularly on measures of executive function.

PLS is not considered hereditary when onset is in adulthood; however, juvenile primary lateral sclerosis (JPLS) has been linked to a mutation in the ALS2 gene which encodes the cell-signalling protein alsin.

The issue of whether PLS exists as a different entity from ALS is not clear, as some patients initially diagnosed as having PLS ultimately develop lower motor neuron signs.

There are no specific tests for the diagnosis of PLS. Therefore, the diagnosis occurs as the result of eliminating other possible causes of the symptoms and by an extended observation period.

Primary lateral sclerosis (PLS) usually presents with gradual-onset, progressive, lower-extremity stiffness and pain due to muscle spasticity. Onset is often asymmetrical. Although the muscles do not appear to atrophy as in ALS (at least initially), the disabling aspect of PLS is muscle spasticity and cramping, and intense pain when those muscles are stretched, resulting in joint immobility. A normal walking stride may become a tiny step shuffle with related instability and falling.

Symptoms of JPLS begin in early childhood and progress over a period of 15 to 20 years. Early symptoms include clumsiness, muscle spasms, weakness and stiffness in the legs, and difficulty with balance. As symptoms progress, they become more serious and include weakness and stiffness in the arms and hands, slurred speech, drooling, difficulty swallowing, and an inability to walk.

Symptoms of MMND begin appearing when people are young, often before the age of 15. An affected individual is generally thin with weak arms and legs. They may lose control of the muscles that control their face, mouth, nose, and throat. This in turn, will cause difficulties speaking and swallowing. Further complications from the loss of facial motor control include drooling, as well facial droop. People with MMND may also suffer from a loss of hearing and sight.

Usually, the first respiratory symptoms are dyspnea and paradoxical respirations which then escalate within the first few months of life to diaphragmatic paralysis. The symptoms of diaphragmatic paralysis come on very rapidly and without warning, and the patient is often rushed to a hospital where they are placed on a ventilator for respiratory support. Due to the severe nature of diaphragmatic paralysis the patient eventually needs continuous ventilation support to survive. Continuous ventilation, however, may in itself cause damage to the anatomy of the lungs.

In addition to diaphragmatic paralysis other issues may arise: as the name suggests, the distal limbs are most affected with symptoms of weakness, restricting mobility due to (near-)paralysis of the distal limbs as well as the head and neck. Also, dysfunction of the peripheral nerves and the autonomic nervous system may occur. Due to these dysfunctions the patients have been shown to suffer from excessive sweating and irregular heartbeat. The deep tendon reflex is also lost in patients with DSMA1.

Uterine growth retardation and poor foetal movement have been observed in severe DSMA1 cases.

Juvenile primary lateral sclerosis (JPLS) ", also known as primary lateral sclerois (PLSJ)," is a rare genetic disorder, with a small number of reported cases, characterized by progressive weakness and stiffness of muscles in the arms, legs, and face. The disorder damages motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.

Neuromuscular disease can be caused by autoimmune disorders, genetic/hereditary disorders and some forms of the collagen disorder Ehlers–Danlos Syndrome, exposure to environmental chemicals and poisoning which includes heavy metal poisoning. The failure of the electrical insulation surrounding nerves, the myelin, is seen in certain deficiency diseases, such as the failure of the body's system for absorbing vitamin B-12

Diseases of the motor end plate include myasthenia gravis, a form of muscle weakness due to antibodies against acetylcholine receptor, and its related condition Lambert-Eaton myasthenic syndrome (LEMS). Tetanus and botulism are bacterial infections in which bacterial toxins cause increased or decreased muscle tone, respectively.Muscular dystrophies, including Duchenne's and Becker's, are a large group of diseases, many of them hereditary or resulting from genetic mutations, where the muscle integrity is disrupted, they lead to progressive loss of strength and decreased life span.

Further causes of neuromuscular diseases are :

Inflammatory muscle disorders

- Polymyalgia rheumatica (or "muscle rheumatism") is an inflammatory condition that mainly occurs in the elderly; it is associated with giant-cell arteritis(It often responds to prednisolone).

- Polymyositis is an autoimmune condition in which the muscle is affected.

- Rhabdomyolysis is the breakdown of muscular tissue due to any cause.

Tumors

- Smooth muscle: leiomyoma (benign)

- Striated muscle: rhabdomyoma (benign)

Motor neuron diseases affect either upper motor neurons (UMN) or lower motor neurons (LMN), or both:

Usually beginning in one or both hands, MMN is characterized by weakness, muscle atrophy, cramping, and often profuse fasciculations (muscle twitching). The symptoms are progressive over long periods, often in a stepwise fashion, but unlike ALS are often treatable.

Sensory nerves are usually unaffected.

Wrist drop and foot drop (leading to trips and falls) are common symptoms. Other effects can include gradual loss of finger extension, leading to a clawlike appearance. Cold & hot temperatures exacerbates MMN symptoms to such an extent, unlike other neuropathies, that it is being investigated as a diagnostic tool.

Some early signs of HIBMs includes:

- Difficulty walking on heels, and difficulty running;

- Weak index finger;

- Frequent loss of balance.

- On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles and accumulation of aberrant proteins similar to those found in senile plaques of Alzheimer's disease (amyloid beta, hyperphosphorylated tau, amongst others)

Neuromuscular disease is a very broad term that encompasses many diseases and ailments that impair the functioning of the muscles, either directly, being pathologies of the voluntary muscle, or indirectly, being pathologies of nerves or neuromuscular junctions.

Neuromuscular diseases are those that affect the muscles and/or their direct nervous system control, problems with central nervous control can cause either spasticity or some degree of paralysis (from both lower and upper motor neuron disorders), depending on the location and the nature of the problem. Some examples of central disorders include cerebrovascular accident, Parkinson's disease, multiple sclerosis, Huntington's disease and Creutzfeldt–Jakob disease. Spinal muscular atrophies are disorders of lower motor neuron while amyotrophic lateral sclerosis is a mixed upper and lower motor neuron condition.

Madras motor neuron disease (MMND) is a motor neuron disease affecting primarily lower motor neurons. It is similar to Monomelic amyotrophy and primarily affects young adults in southern India.

Authors of a large case study, published in 2008, proposed that MMND be divided into two categories: spontaneously-arising MMND and Familial Madras Motor Neuron Disease (FMMND). Using this method, cases in which the disease is inherited would be categorized as FMMND, while cases that displayed no genetic linkage would be categorized as spontaneously-arising MMND.

According to the same study, there is a variant form known as MMNDV, which is classified by additional optic atrophy.

Due to the rareness of MMND, it is classified as a orphan disease.

The extensor Babinski reflex is usually absent. Muscle paresis/paralysis, hypotonia/atonia, and hyporeflexia/areflexia are usually seen immediately following an insult. Muscle wasting, fasciculations and fibrillations are typically signs of end-stage muscle denervation and are seen over a longer time period. Another feature is the segmentation of symptoms – only muscles innervated by the damaged nerves will be symptomatic.

DSMA1 was identified and classified as a sub-group of spinal muscular atrophies (SMA) in 1974. Currently, various classifications include DSMA1 among general spinal muscular atrophies or distal hereditary motor neuropathies, though the latter has been argued to be more correct.

The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS 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 ALS depend on which motor neurons in the body are damaged first.

In limb-onset ALS, people first experience awkwardness when walking or running or even tripping over or stumbling may be experienced and often this is marked by walking with a "dropped foot" which drags gently on the ground. Or if arm-onset, difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock may be experienced.

In bulbar-onset ALS, initial symptoms will mainly be of difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty in 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.

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) although twitching is not a diagnostic symptom and more of a side effect so twitching would either occur after or accompany weakness and atrophy.

Hereditary inclusion body myopathies (HIBM) are a heterogeneous group of very rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

HIBMs are a group of muscle wasting disorders, which are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also been identified in other minorities throughout the world, including people of Asian (Japanese and others), European, and South American origin, as well as Muslim people in the Middle Eastern, Palestinian, and Iranian origin. In Japan and many East Asian countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).

IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts around the age of 20 – 30 years, although young onset at 17 and old onset at 52 has been recorded. As such, it affects the most productive times of our lives. It can progress to marked disability within 10 – 15 years, confining many people with IBM2 to a wheelchair. The weakness and severity can vary from person to person. In some, weakness in the legs is noticed first. In few others, the hands are weakened more rapidly than the legs. Weakness is progressive, which means the muscle becomes weaker over time. IBM2 does not seem to affect the brain, internal organs or sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease, which is the reason IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).

Prognosis for PBP patients is poor. Progressive bulbar palsy symptoms can include progressive difficulty with chewing, talking, and swallowing. Patients can also exhibit reduced gag reflexes, weak palatal movements, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, the patient may be unable to protrude their tongue or manipulate food in their mouth.

Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonants (linguals) and velars, and may show problems with drooling saliva. If the corticobulbar tract is affected a pseudobulbar affect with emotional changes may occur. Because PBP patients have such difficulty swallowing, food and saliva can be inhaled into the lungs. This can cause gagging and choking, and it increases the risk of pneumonia. Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder.

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 or behavioral dysfunction is present in 30–50% of individuals with ALS. Around half of people with ALS will experience mild changes in cognition and behavior, and 10–15% will show signs of frontotemporal dementia. Repeating phrases or gestures, apathy, and loss of inhibition are frequently reported behavioral features of ALS. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS; 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 ALS and increased caregiver burden; this may be due in part to deficits in social cognition. About half the people who have ALS experience emotional lability, in which they cry or laugh for no reason.

Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.

Multifocal motor neuropathy (MMN) is a progressively worsening condition where muscles in the extremities gradually weaken. The disorder, a pure motor neuropathy syndrome, is sometimes mistaken for amyotrophic lateral sclerosis (ALS) because of the similarity in the clinical picture, especially if muscle fasciculations are present. MMN is thought to be autoimmune. It was first described in the mid-1980s.

Unlike ALS which affects both upper and lower motor nerves, MMN involves only lower motor nerves. Nevertheless, definitive diagnosis is often difficult, and many MMN patients labor for months or years under an ALS diagnosis before finally getting a determination of MMN.

MMN usually involves very little pain however muscle cramps, spasms and twitches can cause pain for some sufferers. MMN is not fatal, and does not diminish life expectation. Many patients, once undergoing treatment, only experience mild symptoms over prolonged periods, though the condition remains slowly progressive. MMN can however, lead to significant disability, with loss of function in hands affecting ability to work and perform everyday tasks, and "foot drop" leading to inability to stand and walk; some patients end up using aids like canes, splints and walkers.

A lower motor neuron lesion is a lesion which affects nerve fibers traveling from the ventral horn or anterior grey column of the spinal cord to the relevant muscle(s) – the lower motor neuron.

One major characteristic used to identify a lower motor neuron lesion is flaccid paralysis – paralysis accompanied by loss of muscle tone. This is in contrast to an upper motor neuron lesion, which often presents with spastic paralysis – paralysis accompanied by severe hypertonia.

A motor neuron disease (MND) is any of several neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP) and pseudobulbar palsy. Spinal muscular atrophies (SMA) are sometimes included in the group by some neurologists but it is different disease with clear genetic cause. They are neurodegenerative in nature and cause increasing disability and eventually, death.

Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) is an autosomal dominant neurodegenerative disorder that is defined by extensive involuntary and spontaneous muscle contractions, asthenia, and atrophy with distal sensory involvement following. The disease starts presenting typically in the 40s and is succeeded by a slow and continuous onslaught. Muscle spasms and muscle contractions large in number are noted, especially in the earliest stages. The presentation of HMSN-P is quite similar to amyotrophic lateral sclerosis and has common neuropathological findings. Sensory loss happens as the disease progresses, but the amount of sensation lost varies from case to case. There have been other symptoms of HMSN-P reported such as urinary disturbances and a dry cough.

Two large families in Japan have been identified with the disease locus to chromosome 3q. From descendants of Japan, HMSN-P was brought to Brazil, from there it is a pretty isolated disease. Through clinical studies, researchers identified that TFG mutations on chromosome 3q13.2 causes HMSN-P. "The presence of TFG/ubiquitin- and/or TDP-43-immunopositive cytoplasmic inclusions in motor neurons and cytosolic aggregation composed of TDP-43 in cultured cells expressing mutant TFG indicate a novel pathway of motor neuron death"

BVVL is marked by a number of cranial nerve palsies, including those of the motor components involving the 7th and 9th-12th cranial nerves, spinal motor nerves, and upper motor neurons. Major features of BVVL include facial and neck weakness, fasciculation of the tongue, and neurological disorders from the cranial nerves. The neurological manifestations develop insidiously: they usually begin with sensorineural deafness, progress inexorably to paralysis, and often culminate in respiratory failure. Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts. The first symptoms in nearly all cases of BVVL is progressive vision loss and deafness, and the first initial symptoms are seen anywhere from one to three years.

Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia, retinitis pigmentosa, epilepsy and autonomic dysfunction. Non-neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness, and hypertension.