People with MMND become progressively more weak with time. Generally, affected individuals survive up to 30 years after they are diagnosed.

The three causes of NMT are:

1. Acquired

2. Paraneoplastic

3. Hereditary

The acquired form is the most common, accounting for up to 80 percent of all cases and is suspected to be autoimmune-mediated, which is usually caused by antibodies against the neuromuscular junction.

The exact cause is unknown. However, autoreactive antibodies can be detected in a variety of peripheral (e.g. myasthenia gravis, Lambert-Eaton myasthenic syndrome) and central nervous system (e.g. paraneoplastic cerebellar degeneration, paraneoplastic limbic encephalitis) disorders. Their causative role has been established in some of these diseases but not all. Neuromyotonia is considered to be one of these with accumulating evidence for autoimmune origin over the last few years. Autoimmune neuromyotonia is typically caused by antibodies that bind to potassium channels on the motor nerve resulting in continuous/hyper-excitability. Onset is typically seen between the ages of 15–60, with most experiencing symptoms before the age of 40. Some neuromyotonia cases do not only improve after plasma exchange but they may also have antibodies in their serum samples against voltage-gated potassium channels. Moreover, these antibodies have been demonstrated to reduce potassium channel function in neuronal cell lines.

The long-term prognosis is uncertain, and has mostly to do with the underlying cause; i.e. autoimmune, paraneoplastic, etc. However, in recent years increased understanding of the basic mechanisms of NMT and autoimmunity has led to the development of novel treatment strategies. NMT disorders are now amenable to treatment and their prognoses are good. Many patients respond well to treatment, which usually provide significant relief of symptoms. Some cases of spontaneous remission have been noted, including Isaac's original two patients when followed up 14 years later.

While NMT symptoms may fluctuate, they generally don't deteriorate into anything more serious, and with the correct treatment the symptoms are manageable.

A very small proportion of cases with NMT may develop central nervous system findings in their clinical course, causing a disorder called Morvan's syndrome, and they may also have antibodies against potassium channels in their serum samples. Sleep disorder is only one of a variety of clinical conditions observed in Morvan's syndrome cases ranging from confusion and memory loss to hallucinations and delusions. However, this is a separate disorder.

Some studies have linked NMT with certain types of cancers, mostly lung and thymus, suggesting that NMT may be paraneoplastic in some cases. In these cases, the underlying cancer will determine prognosis. However, most examples of NMT are autoimmune and not associated with cancer.

The severity of symptoms vary widely even for the same type of CMT. There have been cases of monozygotic twins with varying levels of disease severity, showing that identical genotypes are associated with different levels of severity (see penetrance). Some patients are able to live a normal life and are almost or entirely asymptomatic. A 2007 review stated that "Life expectancy is not known to be altered in the majority of cases".

While moderate to severe traumatic brain injury is a risk for ALS, it is unclear if mild traumatic brain injury increases rates.

In 1994 the National Institute for Occupational Safety and Health (NIOSH) reported a nonsignificant increase in nervous system disorders due to four cases of ALS among National Football League (NFL) players. It was unclear if this was due to chance or not. Another study from 2012 also found a possible increase in ALS in NFL football players. An older study did not find an increased risk among high school football players. A 2007 review found an increased risk among soccer players. ALS may also occur more often among the US military veterans however the reason is unknown. This may be due to head injury.

After the 2012 report was released, some NFL players involved in the legal settlement with the NFL complained that the NFL, which initially agreed to pay $765 million, was not doing enough to help players. The judge in the case concurred, and the NFL then agreed to pay an unlimited amount of damages for players found to have ALS, Parkinson's disease, Alzheimer's disease and dementia.

The precise cause of BFS is unknown, and it is not known if it is a disease of the motor nerves, the muscles, or the neuromuscular junction.

Though twitching is sometimes a symptom of serious diseases such as spinal injury, muscular dystrophy, Lyme disease, Creutzfeldt–Jakob disease (CJD), neurofibromatosis or amyotrophic lateral sclerosis (ALS), causes like over-exertion are more common. Mitsikostas "et al." found that fasciculations "were slightly correlated to the body weight and height and to the anxiety level" in normal subjects.

BFS can also be attributed to long term use of anticholinergics such as diphenhydramine and opiates such as morphine, but the latter case is usually when withdrawal symptoms are present.

Magnesium deficiency can cause both fasciculations and anxiety. A vitamin D deficiency may also cause fasciculations, stemming from reduced ionized calcium in the blood (hypocalcemia).

Recent studies have found an association between widespread fasciculations and/or paresthesias with small fiber neuropathy in up to 82% of cases which have a normal EMG and nerve conduction study.

The causes of polyneuropathy can be divided into hereditary and acquired and are therefore as follows:

- "Inherited" -are hereditary motor neuropathies, Charcot–Marie–Tooth disease, and hereditary neuropathy with liability to pressure palsy

- "Acquired" -are diabetes mellitus, vascular neuropathy, alcohol abuse, and Vitamin B12 deficiency

The cause of PBP is unknown. One form of PBP is found to occur within patients that have a CuZn-superoxide dismutase (SOD1) mutation. Progressive bulbar palsy patients that have this mutation are classified with FALS patients, Familial ALS (FALS) accounts for about 5%-10% of all ALS cases and is caused by genetic factors. Within these, about 20-25% are linked to the SOD1 mutation. It is not currently known if and how the decreased SOD1 activity contributes to Progressive Bulbar Palsy or FALS, and studies are being done in patients and transgenic mice to help further understand the impact of this gene on the disease.

A case study was done on a 42-year-old woman who complained of muscle weakness 10 months prior to admission in the hospital. Upon neurological examination, the patient showed muscle atrophy, fasciculation in all limbs and decreased deep tendon reflexes. The patient’s older brother, father, and paternal uncle had previously all died of ALS or an ALS type syndrome. The patient developed Progressive Bulbar Palsy, became dependent on a respirator, and had two episodes of cardiac arrest. The patient died from pneumonia two years after the onset of the disease. After studying the patient, it was found that the patient had a two base pair deletion in the 126th codon in exon 5 of the SOD1 gene. This mutation produced a frameshift mutation, which led to a stop codon at position 131. SOD1 activity was decreased by about 30%. The patient’s histological examination showed severe reduction in lower motor neurons. Upon further study, this case proved to be important because it demonstrated that SOD1 mutations might not effect steady neuropathological changes, and that environmental and genetic factors might affect the phenotype of the SOD1 mutations.

The cause of MMND has not yet been determined. There are cases where MMND appears to be inherited. However, no relevant genes have been identified.

MMND affects many cranial nerves, particularly involving the 7th (facial nerve) and 9th to the 12th cranial nerves (in order: glossopharyngeal nerve, vagus nerve, accessory nerve, spinal accessory nerve).

DSMA1 is usually fatal in early childhood. The patient, normally a child, suffers a progressive degradation of the respiratory system until respiratory failure. There is no consensus on the life expectancy in DSMA1 despite a number of studies being conducted. A small number of patients survive past two years of age but they lack signs of diaphragmatic paralysis or their breathing is dependent on a ventilation system.

Researchers do not fully understand what causes PLS, although it is thought it could be due to a combination of environmental and genetic factors. Studies are being done to evaluate the possible causes, although linking causality can be difficult due to the relatively low number of people who are diagnosed with PLS.

Juvenile PLS may be caused by the ALS2 gene, although this condition is very rare.

The disease has only been identified as distinct from SMA recently, so research is still experimental, taking place mostly in animal models. Several therapy pathways have been devised which include gene therapy, whereby an "IGHMBP2" transgene is delivered to the cell using a viral vector; small-molecule drugs like growth factors (e.g., IGF-1 and VEGF) or olesoxime; and transplantation of healthy motor neurons grown "in vitro" from the patient's stem cells. Studies in amyotrophic lateral sclerosis are also considered helpful because the condition is relatively similar to SMARD1.

Multifocal motor neuropathy is normally treated by receiving intravenous immunoglobulin (IVIG), which can in many cases be highly effective, or immunosuppressive therapy with cyclophosphamide or rituximab. Steroid treatment (prednisone) and plasmapheresis are no longer considered to be useful treatments; prednisone can exacerbate symptoms. IVIg is the primary treatment, with about 80% of patients responding, usually requiring regular infusions at intervals of 1 week to several months. Other treatments are considered in case of lack of response to IVIg, or sometimes because of the high cost of immunoglobulin. Subcutaneous immunoglobulin is under study as a less invasive, more-convenient alternative to IV delivery.

Polyneuropathies may be classified in different ways, such as by "cause", by "presentation", or by "classes" of polyneuropathy, in terms of which part of the nerve cell is affected mainly: the axon, the myelin sheath, or the cell body.

- Distal axonopathy, is the result of interrupted function of the peripheral nerves. It is the most common response of neurons to metabolic or toxic disturbances, and may be caused by metabolic diseases such as diabetes, kidney failure, connective tissue disease, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs such as chemotherapy. They may be divided according to the type of axon affected (large-fiber, small-fiber, or both), the most distal portions of axons are usually the first to degenerate, and axonal atrophy advances slowly toward the nerve's cell body, however if the cause is removed, regeneration is possible, although the prognosis depends on the duration and severity of the stimulus. People with distal axonopathies usually present with sensorimotor disturbances such as amyotrophic lateral sclerosis

- Myelinopathy, is due to a loss of myelin or of the Schwann cells. This demyelination slows down or completely blocks the conduction of action potentials through the axon of the nerve cell(neuraplaxia). The most common cause is acute inflammatory demyelinating polyneuropathy AIDP, the most common form of Guillain–Barré syndrome(although other causes include chronic inflammatory demyelinating polyneuropathy )

- Neuronopathy is the result of issues in the peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies, toxins, or autonomic dysfunction. Neurotoxins such as chemotherapy agents may cause neuronopathies.

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"

Patients can often live with PLS for many years and very often outlive their neurological disease and succumb to some unrelated condition. There is currently no effective cure, and the progression of symptoms varies. Some people may retain the ability to walk without assistance, but others eventually require wheelchairs, canes, or other assistive devices.

Progressive Bulbar Palsy is slow in onset, with symptoms starting in most patients around 50–70 years of age. PBP has a life expectancy typically between 6 months and 3 years from onset of first symptoms. It is subtype of the Motor Neurone Diseases (MND) accounting for around 1 in 4 cases. Amyotrophic lateral sclerosis (ALS) is another sub-type. Pure PBP without any EMG or clinical evidence of abnormalities in the legs or arms is possible, albeit extremely rare. Moreover, about twenty-five percent of patients with PBP eventually develop the widespread symptoms common to ALS.

CMT is a result of genetic mutations in a number of genes. Based on the affected gene, CMT can be categorized into types and subtypes.

The prognosis for those suffering from diagnosed benign fasciculation syndrome is generally regarded as being good to excellent. The syndrome causes no known long-term physical damage. Patients may suffer elevated anxiety even after being diagnosed with the benign condition. Such patients are often directed towards professionals who can assist with reductions and understanding of stress/anxiety, or those who can prescribe medication to help keep anxiety under control.

Spontaneous remission has been known to occur, and in cases where anxiety is thought to be a major contributor, symptoms are typically lessened after the underlying anxiety is treated. In a 1993 study by Mayo Clinic, 121 individuals diagnosed with benign fasciculation syndrome were assessed 2–32 years (~7 years average) after diagnosis. Of those patients there were no cases of BFS progressing to a more serious illness, and 50% of the patients reported significant improvement in their symptoms at the time of the follow-up. Only 4% of the patients reported symptoms being worse than those present at the time of their diagnosis.

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.

The importance of correctly recognizing progressive muscular atrophy as opposed to ALS is important for several reasons.

- 1) the prognosis is a little better. A recent study found the 5-year survival rate in PMA to be 33% (vs 20% in ALS) and the 10-year survival rate to be 12% (vs 6% in ALS).

- 2) Patients with PMA do not suffer from the cognitive change identified in certain groups of patients with MND.

- 3) Because PMA patients do not have UMN signs, they usually do not meet the "World Federation of Neurology El Escorial Research Criteria" for “Definite” or “Probable” ALS and so are ineligible to participate in the majority of clinical research trials such as drugs trials or brain scans.

- 4) Because of its rarity (even compared to ALS) and confusion about the condition, some insurance policies or local healthcare policies may not recognize PMA as being the life-changing illness that it is. In cases where being classified as being PMA rather than ALS is likely to restrict access to services, it may be preferable to be diagnosed as "slowly progressive ALS" or "lower motor neuron predominant" ALS.

An initial diagnosis of PMA could turn out to be slowly progressive ALS many years later, sometimes even decades after the initial diagnosis. The occurrence of upper motor neurone symptoms such as brisk reflexes, spasticity, or a Babinski sign would indicate a progression to ALS; the correct diagnosis is also occasionally made on autopsy.

About 5–10% of cases are directly inherited from a person's parents. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS.

A defect on chromosome 21, which codes for superoxide dismutase, is associated with about 20% of familial cases of ALS, or about 2% of ALS cases overall. 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 mutation is a mutant "SOD1" gene, seen in North America; this is characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A-SOD1, is more slowly progressive than typical ALS, and people with this form of the disorder survive for an average of 11 years.

In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD, and accounts for some 6% of cases of ALS among white Europeans.

Progressive muscular atrophy (PMA), also known as Duchenne-Aran muscular atrophy and by various other names, is a rare subtype of motor neuron disease (MND) that affects only the lower motor neurons. PMA is thought to account for around 4% of all MND cases. This is in contrast to amyotrophic lateral sclerosis (ALS), the most common form of MND, which affects both the upper and lower motor neurones, or primary lateral sclerosis, another rare MND variant, which affects only the upper motor neurons. The distinction is important because PMA is associated with a better prognosis than classic ALS.

The exact mechanisms of these diseases are not well understood. GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins. GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid. However, the part of the dystroglycan that is important in muscle function does not seem to be affected. Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.

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.