Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:

- Hypokalemic periodic paralysis (), where potassium leaks into the muscle cells from the bloodstream.

- Hyperkalemic periodic paralysis (), where potassium leaks out of the cells into the bloodstream.

- Paramyotonia congenita (), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.

- Andersen-Tawil syndrome (), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (syndactyly), crooked fingers (clinodactyly), a small jaw (micrognathia) and low-set ears. Patients need to have another form of periodic paralysis to have the Andersen-Tawil. If a patient has hypo or hyper periodic paralysis they have a 50% chance of getting Andersen-Tawil. They just have to have the gene that causes it. This is a rare occurrence of having this. Only around 100 people in the world are recorded to have it.

Hypokalemic periodic paralysis (hypoKPP) is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis when there is a fall in potassium levels in the blood. In individuals with this mutation, attacks often begin in adolescence and most commonly occur on awakening or after sleep or rest following strenuous exercise (attacks during exercise are rare), high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise, flashing lights and cold temperatures. Weakness may be mild and limited to certain muscle groups, or more severe full-body paralysis. During an attack reflexes may be decreased or absent. Attacks may last for a few hours or persist for several days. Recovery is usually sudden when it occurs, due to release of potassium from swollen muscles as they recover. Some patients may fall into an abortive attack or develop chronic muscle weakness later in life.

Some people only develop symptoms of periodic paralysis due to hyperthyroidism (overactive thyroid). This entity is distinguished with thyroid function tests, and the diagnosis is instead called thyrotoxic periodic paralysis.

Periodic paralysis (also known as myoplegia paroxysmalis familiaris) is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move.

The symptoms of periodic paralysis can also be caused by hyperthyroidism, and are then labeled thyrotoxic periodic paralysis; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.

Patients typically complain of muscle stiffness that can continue to focal weakness. This muscle stiffness cannot be walked off, in contrast to myotonia congenita. These symptoms are increased (and sometimes induced) in cold environments. For example, some patients have reported that eating ice cream leads to a stiffening of the throat. For other patients, exercise consistently induces symptoms of myotonia or weakness. Typical presentations of this are during squatting or repetitive fist clenching. Some patients also indicate that specific foods are able to induce symptoms of paramyotonia congenita. Isolated cases have reported that carrots and watermelon are able to induce these symptoms. The canonical definition of this disorder precludes permanent weakness in the definition of this disorder. In practice, however, this has not been strictly adhered to in the literature.

Although much less publicized, hyperkalemic periodic paralysis has been observed in humans. In humans the disorder causes episodes of extreme muscle weakness, with attacks often beginning in infancy. Depending on the type and severity of the HyperKPP, it can increase or stabilize until the fourth or fifth decade where attacks may cease, decline, or, depending on the type, continue on into old age. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, weather changes, certain pollutants (e.g., cigarette smoke) and fasting. Muscle strength often improves between attacks, although many affected people may have increasing bouts of muscle weakness as the disorder progresses (abortive attacks). Sometimes with HyperKPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependent on the type of myotonia.

Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not rise in response.

In contrast to HyperKPP, hypokalemic periodic paralysis (noted in humans) refers to loss-of-function mutations in channels that prevent muscle depolarisation and therefore are aggravated by low potassium ion concentrations.

This inherited disease is characterized by violent muscle twitching and substantial muscle weakness or paralysis among affected horses. HYPP is a dominant genetic disorder; therefore, heterozygotes bred to genotypically normal horses have a statistic probability of producing clinically affected offspring 50% of the time.

Horses with HYPP can be treated with some possibility of reducing clinical signs, but the degree that medical treatment helps varies from horse to horse. There is no cure. Horses with HYPP often lose muscle control during an attack.

Some horses are more affected by the disease than others and some attacks will be more severe than others, even in the same horse. Symptoms of an HYPP attack may include:

- Muscle trembling

- Prolapse of the third eyelid — this means that the third eyelid flickers across the eye or covers more of the eye than normal

- Generalized weakness

- Weakness in the hind end — the horse may look as though it is 'dog-sitting'

- Complete collapse

- Abnormal whinny — because the muscles of the voicebox are affected as well as other muscles

- Death — in a severe attack the diaphragm is paralyzed and the horse can suffocate

HYPP attacks occur randomly and can strike a horse standing calmly in a stable just as easily as during exercise. Following an HYPP attack, the horse appears normal and is not in any pain which helps to distinguish it from Equine Exertional Rhabdomyolysis (ER), commonly known as "Azoturia," "Monday Morning Sickness" or "tying up." Horses that are tying up usually suffer attacks in connection with exercise and may take anywhere from 12 hours to several days to recover. Muscle tissue is damaged in an attack of ER, and the horse will be in pain during and following an attack. A blood test will reveal elevations in certain muscle enzymes after an episode of ER and so the two diseases, while superficially similar, are easily distinguished from one another in the laboratory.

Unlike with seizures, horses with HYPP are fully conscious and lucid during an attack. Horses may suffocate during an HYPP attack due to paralysis of the respiratory system. Horses that collapse during an episode are clearly distressed as they repeatedly struggle to get to their feet. If this occurs while the horse is being ridden or otherwise handled, the human handler or rider may be at risk of being injured by the movement of the horse.

Diagnosis can be achieved through a specialized form of electromyographic (EMG) testing called the long exercise test. This test measures the amplitude of a nerve response (called the Compound Muscle Action Potential or CMAP) for 40 to 50 minutes following a few minutes of exercise. In affected patients, there is a progressive fall in the amplitude of the potential. Besides the patient history or a report of serum potassium low normal or low during an attack, the long exercise test is the current standard for medical testing. Genetic diagnosis is often unreliable as only a few of the more common gene locations are tested, but even with more extensive testing 20–37% of people with a clinical diagnosis of hypokalemic periodic paralysis have no known mutation in the two known genes. Standard EMG testing cannot diagnose a patient unless they are in a full blown attack at the time of testing. Provoking an attack with exercise and diet then trying oral potassium can be diagnostic, but also dangerous as this form of PP has an alternate form known as hyperkalemic periodic paralysis. The symptoms are almost the same, but the treatment is different. The old glucose insulin challenge is dangerous and risky to the point of being life-threatening and should never be done when other options are so readily available.

People with hypokalemic periodic paralysis are often misdiagnosed as having a conversion disorder or hysterical paralysis since the weakness is muscle-based and doesn't correspond to nerve or spinal root distributions. The tendency of people with hypokalemic periodic paralysis to get paralyzed when epinephrine is released in "fight or flight" situations further adds to the temptation to misdiagnose the disorder as psychiatric.

Paramyotonia congenita (PC), also known as paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.

Episodic ataxia type-3 (EA3) is similar to EA1 but often also presents with tinnitus and vertigo. Patients typically present with bouts of ataxia lasting less than 30 minutes and occurring once or twice daily. During attacks, they also have vertigo, nausea, vomiting, tinnitus and diplopia. These attacks are sometimes accompanied by headaches and precipitated by stress, fatigue, movement and arousal after sleep. Attacks generally begin in early childhood and last throughout the patients' lifetime. Acetazolamide administration has proved successful in some patients. As EA3 is extremely rare, there is currently no known causative gene. The locus for this disorder has been mapped to the long arm of chromosome 1 (1q42).

Hypokalemic sensory overstimulation is a term coined by MM Segal to describe a syndrome that has been reported in a single case-study by his group. Segal describes the syndrome as a form of neurological disorder that has similarities to attention deficit hyperactivity disorder and has several similarities to disorders of ion channels, in particular to the muscle disorder hypokalemic periodic paralysis.

It is medically related to disorders of ion channels, in particular to the muscle disorder hypokalemic periodic paralysis and is similar in nature to ADHD, as the prominent feature of hypokalemic sensory overstimulation is the feeling of sensory overstimulation that is also characteristic of attention deficit disorder and the over stimulation of the nervous system.. It may also be connected with premenstrual syndrome and the body's natural sodium levels.

The most distinctive clinical feature is the absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation. There is also a high prevalence of breech presentation. Other symptoms include weak or absent suck and poor tone, poor suck and misdirected swallowing, and red blotching of skin.

Symptoms in an older child with familial dysautonomia might include:

1. Delayed speech and walking

2. Unsteady gait

3. Spinal curvature

4. Corneal abrasion

5. Less perception in pain or temperature with nervous system.

6. Poor growth

7. Erratic or unstable blood pressure.

8. Red puffy hands

9. Dysautonomia crisis: a constellation of symptoms in response to physical and emotional stress; usually accompanied by vomiting, increased heart rate, increase in blood pressure, sweating, drooling, blotching of the skin and a negative change in personality.

Typically, episodic ataxia presents as bouts of ataxia induced by startle, stress, or exertion. Some patients also have continuous tremors of various motor groups, known as myokymia. Other patients have nystagmus, vertigo, tinnitus, diplopia or seizures.

Hypokalemic sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate. The phenotype overlaps with that of attention deficit disorder, raising the possibility of subtypes of attention deficit disorder that have a peripheral sensory cause and possible new forms of therapy.

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.

An attack often begins with muscle pain, cramping, and stiffness. This is followed by weakness or paralysis that tends to develop rapidly, usually in late evening or the early hours of the morning. The weakness is usually symmetrical; the limb muscles closer to the trunk (proximal) are predominantly affected, and weakness tends to start in the legs and spread to the arms. Muscles of the mouth and throat, eyes, and breathing are usually not affected, but occasionally weakness of the respiratory muscles can cause life-threatening respiratory failure. Attacks typically resolve within several hours to several days, even in the absence of treatment. On neurological examination during an attack, flaccid weakness of the limbs is noted; reflexes are usually diminished, but the sensory system is unaffected. Mental status is not affected.

Attacks may be brought on by physical exertion, drinking alcohol, or eating food high in carbohydrates or salt. This may explain why attacks are more common in summer, when more people drink sugary drinks and engage in exercise. Exercise-related attacks tend to occur during a period of rest immediately after exercise; exercise may therefore be recommended to abort an attack.

There may be symptoms of thyroid overactivity, such as weight loss, a fast heart rate, tremor, and perspiration; but such symptoms occur in only half of all cases. The most common type of hyperthyroidism, Graves' disease, may additionally cause eye problems (Graves' ophthalmopathy) and skin changes of the legs (pretibial myxedema). Thyroid disease may also cause muscle weakness in the form of thyrotoxic myopathy, but this is constant rather than episodic.

FLD produces rapidly progressive weakness of tongue, face and pharyngeal muscles in a clinical pattern similar to myasthenia. Neuromuscular transmission may be abnormal in these muscles because of rapid denervation and immature reinnervation. Paralysis occurs secondary to degeneration of the motor neurons of the brain stem. It causes progressive bulbar paralysis due to involvement of motor neurons of the cranial nerve nuclei. The most frequent symptoms at onset of progressive bulbar paralysis of childhood has been a unilateral facial paralysis. It is followed in frequency by dysarthria due to facial weakness or by dysphagia. Palatal weakness and palpebral ptosis also have been reported in few patients. Both sexes can be affected.

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.

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.

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)

Familial dysautonomia (FD), sometimes called Riley–Day syndrome and hereditary sensory and autonomic neuropathy type III (HSAN-III), is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms, including insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Drs. Conrad Milton Riley (1913–2005) and Richard Lawrence Day (1905–1989) in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSAN). All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.

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.

Symptoms include intrinsic minus hand deformity, paralysis of intrinsic hand muscles, and C8/T1 Dermatome distribution numbness. Involvement of T1 may result in Horner's syndrome, with ptosis, and miosis. Weakness or lack of ability to use specific muscles of the shoulder or arm.It can be contrasted to Erb-Duchenne's palsy, which affects C5 and C6.

The syndrome typically presents as a progressive flaccid symmetric paralysis with areflexia, often causing respiratory failure. Electromyographic studies and nerve conduction studies show normal motor conduction velocity and latency with decreased amplitude of compound muscle action potentials. F wave and sensory nerve action potentials are often normal in this illness. Pathologically, it is a noninflammatory axonopathy without demyelination. Antibodies attack the coating of the motor neurons without causing inflammation or loss of myelin. It does not affect sensory neurons, so sensation remains intact despite loss of movement.

Fazio–Londe disease (FLD), also called progressive bulbar palsy of childhood, is a very rare inherited motor neuron disease of children and young adults and is characterized by progressive paralysis of muscles innervated by cranial nerves.

The classic presentation of Todd's paresis is a transient weakness of a hand, arm, or leg after focal seizure activity within that limb. The weakness may range in severity from mild to complete paralysis.

When seizures affect areas other than the motor cortex, other transient neurological deficits can take place. These include sensory changes if the sensory cortex is involved by the seizure, visual field defects if the occipital lobe is involved, and aphasia if speech, comprehension or conducting fibers are involved.

Postictal paresis (PP), although familiar to neurologists, has not been well-studied. One retrospective observational study evaluated 328 selected patients from ages 16 to 57 years who had prolonged video-electroencephalogram (EEG) monitoring for medically intractable epilepsy and focal seizure onset; those with nonepileptic seizures, status epilepticus, and Lennox-Gastaut syndrome were excluded. The following observations were made:

- PP occurred in 44 patients (13.4 percent)

- PP was always unilateral and always contralateral to the seizure focus

- The mean duration of PP was 174 seconds (range 11 seconds to 22 minutes)

Of all seizures followed by PP, the following features were noted:

- Obvious ictal motor activity was seen in 78 percent (Todd's paresis is more common after any clonic seizure activity)

- Very slight ictal motor activity was seen in 10 percent

- No ictal motor activity was seen in nearly 10 percent

- The most common ictal lateralizing sign was unilateral clonic activity in 56 percent

- Ictal dystonic posturing occurred in 48 percent

- Ictal limb immobility occurred in 25 percent

The results of this study are valuable because few other data exist on the frequency, duration, and seizure characteristics associated with PP. However, the study is likely biased by the inclusion only of patients with medically intractable seizures who had undergone video-EEG monitoring, and the results may not extrapolate to a general epilepsy population.

Other post-ictal neurological findings that do not involve activity of the area affected by the seizure have been described. They are thought to be caused by a different mechanism than Todd's paresis, and including paralysis of the contralateral limb, and rare genetic causes of hemiplegia and seizures.